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ОбложкаJain K.K. Applications of biotechnology in neurology. - New York: Springer Science + Business Media: Humana press, 2013. - xxxv, 638 p.: ill., tab. - (Biomedicine). - Incl. bibl. ref. - Ind.: p.613-638. - ISBN 978-1-62703-271-1
Шифр: (И/Р-J19) 02
 

Место хранения: 02 | Отделение ГПНТБ СО РАН | Новосибирск

Оглавление / Contents
 
1  Introduction to Neurobiotechnology ........................... 1
   Definitions and History ...................................... 1
   Molecular Neurology .......................................... 2
   Molecular Neuroscience ....................................... 2
   Relationships of Biotechnologies to Neurology ................ 3
   References ................................................... 4
2  Neurogenetics and Neurogenomics .............................. 7
   Introduction ................................................. 7
   Neurogenetics ................................................ 7
      Neurogenomics ............................................. 8
      Variations in the Human Genome ............................ 8
      Technologies Used in Neurogenomics ........................ 9
   Applications of Neurogenomics ............................... 12
   References .................................................. 15
3  Neuroproteomics ............................................. 17
   Introduction ................................................ 17
   Proteomic Technologies ...................................... 17
   Application of Proteomics for the Study of Nervous
   System ...................................................... 18
      Study of Synapses ........................................ 19
      Study of Neurotransmitters ............................... 19
      Study of Neuronal Receptors .............................. 20
      Study of Regeneration and Degeneration of the Nervous
      System ................................................... 20
      Proteomics of Blood-Brain Barrier ........................ 20
   Proteomics for Study of Neurological Disorders .............. 21
      Proteomics of Prion Diseases ............................. 21
      Protein Misfolding and Neurodegenerative Disorders ....... 23
      Ion Channel Link for Protein-Misfolding Disease .......... 24
      Detection of Misfolded Proteins  v ....................... 24
      Neurodegenerative Disorders with Protein Abnormalities ... 24
      Proteomics and Glutamate Repeat Disorders ................ 30
      Proteomics and Demyelinating Diseases .................... 32
      Proteomics of Neurogenetic Disorders ..................... 32
      Quantitative Proteomics and Familial Hemiplegic
      Migraine ................................................. 34
      Proteomics of Spinal Muscular Atrophy .................... 34
      Proteomics of CNS Trauma ................................. 34
      Neuroproteomics of Epilepsy .............................. 36
      Proteomics of CNS Aging .................................. 36
      Neuroproteomics of Psychiatric Disorders ................. 37
   Neurodiagnosties Based on Proteomics ........................ 39
      Disease-Specific Proteins in the Cerebrospinal Fluid ..... 39
      CNS Tissue Proteomics .................................... 40
      Diagnosis of CNS Disorders by Examination of Proteins
      in Urine ................................................. 42
      Diagnosis of CNS Disorders by Examination of Proteins
      in the Blood ............................................. 42
   Future Prospects of Neuroproteomics in Neurology ............ 44
      HUPO 's Pilot Brain Proteome Project ..................... 45
   References .................................................. 46
4  Biomarkers of Neurological Disorders ........................ 49
   Introduction ................................................ 49
   Biomarkers of Neurological Disorders ........................ 50
   Discovery of Biomarkers for Neurological Disorders .......... 50
      Biomarker Identification in the CSF Using Proteomics ..... 51
      Biomarker Identification in the CSF Using Lipidomics ..... 52
      Cerebral Microdialysis for the Study of Biomarkers
      of Cerebral Metabolism ................................... 52
      Detection of Protein Biomarkers of CNS Disorders in the
      Blood .................................................... 53
      Brain Imaging for Detection of Biomarkers ................ 53
   Biomarkers of the Aging Brain ............................... 54
      Cellular Biomarker of Aging of the Brain ................. 54
      CSF F2-Isoprostanes as Biomarker of Aging Brain .......... 54
      Protein Aggregation as a Biomarker of Aging Brain ........ 55
   Data Mining for Biomarkers of Neurological Disorders ........ 55
   Antibodies as Biomarkers in Disorders of the Nervous
   System ...................................................... 56
   Biomarkers of Neural Regeneration ........................... 56
   Biomarkers of Disruption of Blood-Brain Barrier ............. 57
   Biomarkers of Neurotoxicity ................................. 57
      Glial Fibrillary Acidic Protein as Biomarker of
      Neurotoxicity ............................................ 58
      Single-Stranded DNA as a Biomarker of Neuronal 
      Apoptosis ................................................ 58
   Biomarkers of Neurogenetic Disorders ........................ 59
      Charcot-Marie Tooth Disease .............................. 59
      Duchenne and Becker Muscular Dystrophy ................... 60
      Fragile X Syndrome ....................................... 61
      Hereditary Neuropathy with Liability to Pressure
      Palsies .................................................. 62
      Hereditary Metabolic Storage Disorders with Neurologic
      Manifestations ........................................... 62
      Mitochondrial Disorders Affecting the Nervous System ..... 63
      Spinal Muscular Atrophy .................................. 64
   Biomarkers of Neurodegenerative Disorders ................... 64
   Biomarkers of Alzheimer's Disease ........................... 65
      The Ideal Biomarker for AD ............................... 68
      Methods for Determining Biomarkers of AD ................. 69
      Biomarkers of AD in CSF .................................. 76
      Blood Biomarkers of AD ................................... 82
      Urine Tests for AD ....................................... 85
      A Biomarker-Based Skin Test for AD ....................... 86
      Salivary Biomarkers of AD ................................ 86
      Applications of Biomarkers of AD ......................... 87
      Concluding Remarks About Biomarkers for AD and Future
      Prospects ................................................ 89
   Biomarkers of Parkinson's Disease ........................... 90
      Biomarkers of PD Based on Gene Expression in Blood ....... 91
      Cardiac Denervation as a Biomarker of PD ................. 91
      Imaging Biomarkers of PD ................................. 92
      Metabolic Brain Networks as Biomarkers ................... 93
      Metabonomic Biomarker Profile for Diagnosis
      and Monitoring of PD ..................................... 93
      Protein Вiomarkers of PD ................................. 94
      Serum Vitamin D as a Biomarker of PD ..................... 94
      Future Prospects for Biomarkers of PD .................... 95
   Biomarkers of Huntington's Disease .......................... 95
      Quantitative MRI Measurement of Brain Atrophy
      as Biomarker of HD ....................................... 97
   Biomarkers of Wilson's Disease .............................. 97
   Biomarkers of Amyotrophic Lateral Sclerosis ................. 98
      Biomarkers of Neuroinflammation in ALS ................... 98
      Detection of ALS Biomarkers in Blood vs CSF .............. 99
      Ideal Biomarker of ALS ................................... 99
      Imaging Biomarkers of ALS ............................... 100
      Metabolomic Biomarkers of ALS ........................... 100
      Proteomic Вiomarkers of ALS ............................. 101
      Future Prospects of Biomarkers of ALS ................... 101
   Biomarkers of Dementia in HIV-1 -Infected Patients ......... 102
   Biomarkers of Prion Diseases ............................... 102
      14-3-3 Protein and tTau/P-Tau Ratio ..................... 103
      Bioluminescence Imaging as a Surrogate Biomarker
      of Prion Infectivity .................................... 103
   Biomarkers of Multiple Sclerosis ........................... 103
      Antibodies in Multiple Sclerosis ........................ 104
      CSF Cystatin С as a Biomarker of Multiple Sclerosis ..... 106
      T Cells as Biomarkers of Multiple Sclerosis ............. 106
      Matrix Metalloproteinases as Biomarkers in Multiple
      Sclerosis ............................................... 107
      Gelsolin as a Biomarker of Multiple Sclerosis ........... 107
      Gene Expression Profiling of Biomarkers in Multiple
      Sclerosis ............................................... 108
      Serum Proteomic Pattern Analysis in Multiple Sclerosis .. 108
      Brain Imaging Biomarkers of Multiple Sclerosis .......... 108
      Biomarkers of Response to Therapy of Multiple
      Sclerosis ............................................... 110
      Concluding Remarks and Future Perspective for 
   Biomarkers of Multiple Sclerosis ........................... 110
      Biomarkers of Cerebrovascular Disorders ................. 112
      Biomarkers of Stroke .................................... 112
      Biomarkers of Cerebral Vasospasm ........................ 120
      Biomarkers of Intracerebral Hemorrhage .................. 120
      Biomarkers of Hypoxic Brain Damage ...................... 121
      D-dimer as a Biomarker of Cerebral Venous Thrombosis .... 121
   Biomarkers of Traumatic Brain Injury ....................... 122
      Technologies for Identification of Biomarkers of TBI .... 122
      Biomarkers of TBI ....................................... 124
      Biomarkers of Inflicted TBI in Infants .................. 127
      Clinical Applications of Biomarkers of TBI .............. 128
   Biomarkers of CNS Infections ............................... 129
      Biomarkers of Вacterial Meningitis ...................... 129
      Biomarkers of Viral Infections of CNS ................... 129
   Biomarkers of Epilepsy ..................................... 131
      Genetic Epilepsies ...................................... 131
      Biochemical Markers of Epilepsy ......................... 131
      Biomarkers of Temporal Lobe Epilepsy .................... 132
      Imaging Biomarkers of Epilepsy .......................... 132
   Biomarkers of Normal Pressure Hydrocephalus ................ 133
   Biomarkers of Retinal Disorders ............................ 133
      Biomarkers of Age-Related Macular Degeneration .......... 133
   Biomarkers of Sleep Disorders .............................. 134
      Biomarker of Excessive Daytime Sleepiness ............... 134
      Biomarkers of Obstructive Sleep Apnea ................... 135
      Biomarkers of Restless Legs Syndrome .................... 135
   Biomarkers of Pain ......................................... 136
      Biomarkers of Neuropathic Pain .......................... 136
      Brain Insular Glutamate as Biomarker of Fibromyalgia .... 137
      Biomarkers of Visceral Pain ............................. 137
      Вiomarkers of Migraine .................................. 138
   Biomarkers of Myalgic En cephalomyelitis/Chronic
   Fatigue Syndrome ........................................... 138
   Biomarkers of Psychiatric Disorders ........................ 139
      Anorexia Nervosa ........................................ 139
      Attention-Deficit Hyperactivity Disorder ................ 139
      Biomarkers for Autism ................................... 140
      Biomarkers of Depression ................................ 141
      Biomarkers of Psychosis ................................. 142
      Biomarkers of Schizophrenia ............................. 142
   References ................................................. 145
5  Molecular Diagnostics for Neurological Disorders ........... 155
   Introduction ............................................... 155
      Technologies ............................................ 155
      Molecular Brain Imaging ................................. 157
      Applications of Sequencing in Molecular Diagnostics ..... 159
   Clinical Applications ...................................... 160
   Molecular Diagnosis of Neurogenetic Disorders .............. 160
      Introduction ............................................ 160
      Applications ............................................ 160
      Alzheimer Disease ....................................... 163
      Familial Amyotrophic Lateral Sclerosis .................. 164
      Down Syndrome ........................................... 165
      Molecular Diagnosis of Wilson's Disease ................. 165
      Neuromuscular Disorders ................................. 166
      Triple Repeat Disorders ................................. 167
      Mitochondrial Disorders Affecting the Nervous System .... 170
      Epilepsy ................................................ 171
      Hereditary Metabolic Disorders with Neurologic
      Manifestations .......................................... 172
      Hereditary Motor and Sensory Neuropathies ............... 173
      Parkinson Disease ....................................... 175
      Autism Spectrum Disorders ............................... 175
      Attention Deficit Hyperactivity Disorder ................ 176
      Advantages and Limitations of Molecular Diagnostics
      of Genetic Disorders .................................... 177
   Molecular Diagnosis of CNS Infections ...................... 177
      Introduction ............................................ 177
      Indications ............................................. 178
      Detection of Viral Infections of the Nervous System ..... 179
      Molecular Methods for Detection of Bacterial, Fungal
      and Protozoal Infections ................................ 184
      Neurocysticercosis ...................................... 188
      Limitations and Pitfalls of Molecular Diagnosis of
      Infections .............................................. 189
   Molecular Diagnosis of Brain Tumors ........................ 189
      Introduction ............................................ 189
      Molecular Diagnostic Technologies Relevant to Brain
      Tumors .................................................. 190
      Genetic Alterations Underlying the Pathogenesis
      of Brain Tumors ......................................... 196
      Advantages and Limitations of Molecular Diagnostics
      of Brain Tumors ......................................... 205
      Concluding Remarks on Molecular Diagnosis of Brain 
      Tumors .................................................. 206
   References ................................................. 206
6  Molecular Neuropharmacology ................................ 211
   Introduction ............................................... 211
   Impact of Biotechnology on Neuropharmacology ............... 211
      Pharmacogenetics and Neuropharmacology .................. 212
      Biotechnology and Pharmacokinetics ...................... 212
      Biotechnology and Pharmacodynamics ...................... 214
      Biomarkers and Neuropharmacology ........................ 214
   Role of Genomics in Neuropharmacology ...................... 215
      Pharmacogenomics ........................................ 215
      Role of DNA Sequencing in Drug Discovery and
      Development ............................................. 216
      Application of Synthetic Biology in Drug Discovery ...... 216
      Role of Antisense in Drug Discovery for Neurological
      Disorders ............................................... 217
      Role of RNAi in Drug Discovery for Neurological
      Disorders ............................................... 218
   Role of Proteomics in Neuropharmacology .................... 218
      Proteomics for Drug Discovery ........................... 218
      Proteins as Drug Targets ................................ 219
      Pharmacoproteomics ...................................... 220
      Global Proteomics for Pharmacodynamics .................. 220
      Integration of Proteomics with Genomics for Drug
      Discovery ............................................... 221
   Cell-Based Drug Discovery .................................. 221
      Advantages and Pitfalls of Cell-Based Assays for Drug
      Discovery ............................................... 221
      Stem Cells for Drug Discovery ........................... 222
   References ................................................. 224
7  Ion Channels and Neurology ................................. 227
      Introduction ............................................ 227
      Historical Aspects ...................................... 227
   Ion Channels in the Nervous System ......................... 228
      Voltage-Gated Channels .................................. 228
      Potassium Channels ...................................... 228
      Sodium Channels ......................................... 229
      Calcium Channels ........................................ 229
      Chloride Channels ....................................... 230
      Aquporins ............................................... 231
      Gap Junctions ........................................... 231
      Ligand-Gated and Transmitter-Gated Ion Channels ......... 231
   Structure and Function of Ion Channels ..................... 232
      Molecular Structure of Ion Channels ..................... 232
      Physiology of Ion Channels .............................. 233
      Role of Ion Channels in the Nervous System .............. 233
   Genomics and Ion Channels .................................. 234
   Role of Ion Channels in Pathophysiology of Neurologic
   Disorders .................................................. 235
      Inherited Neurologic Channelopathies .................... 235
      Acquired or Secondary Neurologic Channelopathies ........ 236
      Pathomechanism of Disease Due to Mutated Proteins ....... 238
   Channelopathies According to Channel Involved .............. 239
      Potassium Channelopathies ............................... 239
      Calcium Channelopathies ................................. 240
      Sodium Channelopathies .................................. 240
      Chloride Channelopathies ................................ 241
   Ion Channels and Pain ...................................... 241
      Role of Ion Channels in Pathomechanism of Pain .......... 241
      Ion Channels as Targets for Pain Therapeutics ........... 241
   Role of Ion Channels in Management of Neurologic
   Disorders .................................................. 242
      Role of Ion Channels in Clinical Neuropharmacology ...... 242
   Concluding Remarks and Future Prospects .................... 245
   References ................................................. 246
8  Role of Nitric Oxide in Neurological Disorders ............. 249
   Introduction ............................................... 249
   Role of NO in the Nervous System ........................... 250
      Neurovascular Coupling of COX-2 and nNOS ................ 251
      Neuroglobin ............................................. 251
      Acute Actions of NO in the CNS Pathways ................. 252
      Role of NO in Memory and Learning ....................... 252
      Role of NO in Synaptic Plasticity ....................... 253
      Role of NO in the Peripheral Nervous System ............. 253
      NO and Neuroendocrine Function .......................... 253
   NO-Based Therapies for Neurological Disorders .............. 254
   Role of NO in Neurodegenerative Disorders .................. 254
      NO-induced Mitochondrial Dysfunction in
      Neurodegeneration ....................................... 254
      White Matter Disorders .................................. 255
      Alzheimer's Disease ..................................... 256
      Role of NO in Pathophysiology of AD ..................... 256
      Role of ApoE Genotype ................................... 257
      NO-based Therapies for AD ............................... 259
      Parkinson Disease ....................................... 260
      Potential of NO-based Therapies for PD .................. 262
      NO and Amyotrophic Lateral Sclerosis .................... 262
   Stroke ..................................................... 263
   Pathophysiology of Cerebral Ischemia ....................... 263
   Role of NO in Cerebral Ischemia ............................ 263
   Basis of Use of NO-based Treatment in Cerebrovascular
   Ischemia ................................................... 265
   Use of NO Donors in Cerebral Ischemia ...................... 266
   Use of NO Donors in Cerebral Reperfusion Injury ............ 267
   Attenuation of NO for Neuroprotection in Cerebral
   Ischemia ................................................... 267
   Role of NO in Neuroprotection in Cerebral Ischemia ......... 268
   eNOS Gene Polymorphisms as Predictor of Cerebral
   Aneurysm Rupture ........................................... 268
      Role of NO in Assessment of Cerebral and Retinal Blood
      Flow .................................................... 269
      Stroke and Heart Disease ................................ 269
      Cerebral Vasospasm and NO ............................... 269
      NOS Gene Therapy for Cerebral Vasospasm ................. 270
   NO and Traumatic Brain Injury .............................. 271
      Role of NO in Pathophysiology of TBI .................... 272
      Role of NO in the Treatment of Traumatic Brain Injury ... 273
   NO and Epilepsy ............................................ 273
      Role of NO in Peripheral Neuropathy ..................... 274
      iNOS Induction in Experimental Allergic Neuritis ........ 274
   Role of NO in Sciatica ..................................... 275
   Neuroinflammatory Disorders ................................ 275
      NO and Muscular Dystrophy ............................... 276
      Basis for the Use of NO in Muscular Dystrophies ......... 276
      NO and Duchenne Muscular Dystrophy ...................... 276
   NO and Vestibulotoxicity ................................... 277
   NO and Blood-Brain Barrier ................................. 277
      Role of NO in the BBB ................................... 277
      NO for Opening the BBB .................................. 278
   Role of NO in Pain ......................................... 278
      NO-Based Therapies for Pain ............................. 278
      Treatment of Diabetic Neuropathy with Isosorbide
      Dinitrate Spray ......................................... 279
      NO-Based Therapies for Migraine ......................... 279
   Concluding Remarks ......................................... 280
   References ................................................. 280
9  Nanoneurology .............................................. 283
   Introduction ............................................... 283
   Nanobiotechnology for Neurophysiological Studies ........... 283
      Use of Nanoelectrodes in Neurophysiology ................ 283
      Gold Nanoparticles for In Vivo Study of Neural 
      Function ................................................ 284
   Nanodiagnosis and Nanoparticle-Based Brain Imaging ......... 284
      Applications of Nanotechnology in Molecular Imaging
      of the Brain ............................................ 284
      Nanoparticles and MRI for Macrophage Tracking in the
      CNS ..................................................... 285
      Nanoparticles for Tracking Stem Cells for Therapy
      of CNS Disorders ........................................ 286
      Multifunctional NPs for Diagnosis and Treatment
      of Brain Disorders ...................................... 287
   Nanotechnology-Based Drug Delivery to the CNS .............. 287
      Nanoencapsulation for Delivery of Vitamin E for CNS
      Disorders ............................................... 287
      Nanoparticle Technology for Drug Delivery Across BBB .... 288
   Nanobiotechnology and Neuroprotection ...................... 289
   Nanotechnology-Based Devices and Implants for CNS .......... 290
      Nanowire Neuroprosthetics with Functional Membrane
      Proteins ................................................ 291
      Nanotube-Neuron Electronic Interface .................... 291
      Nanobiotechnology-Based Devices for Restoration
      of Neural Function ...................................... 292
   Concluding Remarks and Future Prospects of Nanoneurology ... 292
   References ................................................. 293
10 Neurotrophic Factors ....................................... 295
   Introduction ............................................... 295
      Historical Aspects of Neurotrophic Factors .............. 295
      Classification of Neurotrophic Factors .................. 295
   Description of Neurotrophic Factors ........................ 295
      Neurotrophin Family ..................................... 295
      Neurotrophic Factor Receptors ........................... 305
      Axonal Transport of Nerve Growth Factors ................ 306
      Role of Neurotrophic Factors in Neuronal Development,
      Maturation, and Survival ................................ 306
      Role of Neurocytokines and Neurotrophic Factors
      in Cell Signaling ....................................... 308
      Hedgehog Family of Inducing Proteins .................... 310
      Proteins Involved in Neuromuscular Development .......... 311
      Neuroimmunophilins ...................................... 311
      Role of Neurotrophic Factors in Action of
      Antidepressants ......................................... 312
      Role of Neurotrophic Factors in Brain Inflammation ...... 312
      Effect of Exercise on Serum Neurotrophic Factors ........ 313
   Methods of Delivery of Neurotrophic Factors ................ 313
   Clinical Applications of NTFs .............................. 314
      Neurotrophic Factors as Neuroprotective Agents .......... 315
      Neurotrophic Factors and Oxidative Stress ............... 317
      Neurotrophic Factors for Seizures ....................... 317
   NTFs for Neurodegenerative Disorders ....................... 317
      Scientific Basis of Effect of NTFs in
      Neurodegenerative Disorders ............................. 317
      Alzheimer Disease ....................................... 318
      Parkinson Disease ....................................... 320
      Amyotrophic Lateral Sclerosis ........................... 323
      Huntington Disease ...................................... 325
      NTFs for Treatment of Stroke ............................ 326
      Molecular Mechanisms in Ischemic Stroke ................. 327
      Role of Neurotrophic Factors in Central Nervous System
      Injury .................................................. 328
      Changes in Neurotrophic Factor Associated with
      Cerebral Ischemia ....................................... 328
      Potential Role of Neurotrophic Factors in the Treatment
      of Cerebral Ischemia .................................... 329
      Method of Administration of Neurotrophic Factors
      for Cerebral Ischemia ................................... 332
   Use of Neurotrophic Factors as Neuroprotective Agents ...... 332
   Other Agents Mimicking Neurotrophic Factors ................ 333
      Role of NTFs in Action of Stem Cell Therapy
      for Cerebral Ischemia ................................... 333
      oncluding Remarks About Use of NTFs in Stroke ........... 334
   Role of NTFs in Traumatic Injuries to the Nervous
   System ..................................................... 334
      Traumatic Brain Injury .................................. 335
      Spinal Cord Injury ...................................... 338
      Peripheral Nerve Injuries ............................... 342
   Treatment of Peripheral Neuropathies with NTFs ............. 344
      Diabetic Neuropathy ..................................... 345
      Antineoplastic Agents-Induced Neuropathy ................ 349
      Motor Neuropathies ...................................... 350
      Neurotrophic Factors and Neuropathic Pain ............... 350
      Delivery of NTFs for Peripheral Neuropathies ............ 351
      Contraindications for Use of NTFs in Peripheral
      Neuropathies ............................................ 351
      Future Prospects of NTFs for the Treatment
   of Peripheral Neuropathies ................................. 352
   Adverse Effects of NTFs .................................... 352
   Concluding Remarks and Future Prospects .................... 353
   References ................................................. 354
11 Cell Therapy of Neurological Disorders ..................... 361
   Introduction ............................................... 361
   Historical Landmarks in Cell Therapy of Neurological
   Disorders .................................................. 362
   Rationale of Cell Therapy for Neurologic Disorders ......... 362
   Sources of Cells ........................................... 362
      Types of Cells that Are Used for Cell Implantation for
      in CNS .................................................. 364
      Stem Cell Transplantation ............................... 365
      Indications for Cell Therapy of Neurological Disorders .. 366
   Cell Therapy of Neurodegenerative Disorders ................ 367
      Cell Therapy of Amyotrophic Lateral Sclerosis ........... 367
      Cell Therapy for Parkinson Disease ...................... 368
      Cell Therapy for Huntington Disease ..................... 368
      Cell Therapy for Alzheimer Disease ...................... 370
   Cell Transplants for Demyelinating Disorders ............... 370
   Cell Therapy for Stroke .................................... 371
   Cell Therapy of Epilepsy ................................... 372
   Management of Chronic Intractable Pain by Cell Therapy ..... 373
      Implantation of Chromaffin Cells ........................ 373
      Role of Stem Cells in Management of Pain ................ 374
      Implantation of Astrocytes Secreting Enkephalin ......... 374
      Cells for Delivery of Antinociceptive Molecules ......... 374
      Implantation of Genetically Engineered Cells ............ 375
   Clinical Trials of Cell Therapy of Neurological Disorders .. 375
   Adverse Effects of Cell Therapy ............................ 375
   Future Prospects for Cell Therapy of CNS Disorders ......... 379
   References ................................................. 380
12 Gene Therapy of Neurological Disorders ..................... 383
   Introduction ............................................... 383
   Historical Evolution of Gene Therapy ....................... 383
   Indications ................................................ 385
   Methods of Gene Therapy .................................... 385
      Classification .......................................... 385
      Techniques of Gene Therapy Relevant to the Nervous
      System .................................................. 385
      Viral Vectors for Gene Therapy .......................... 389
      Nonviral Vectors for Gene Therapy ....................... 393
      Ideal Vector for Gene Therapy of Neurologic Disorders ... 396
      Promoters of Gene Transfer .............................. 396
      RNA Trans-Splicing ...................................... 397
      Antisense Therapy ....................................... 397
      RNA Interference and Gene Therapy ....................... 398
   Delivery of Genes to the CNS ............................... 398
      Routes of Delivery of Genes to the CNS .................. 398
      Introduction of Antisense Compounds into the CSF
      Pathways ................................................ 400
      Delivery of Gene Therapy to the Peripheral Nervous
      System .................................................. 400
      Cell-Mediated Gene Therapy .............................. 401
      Targeted and Controlled Gene Therapy .................... 404
      Monitoring of Gene Therapy .............................. 404
   Applications of Gene Therapy in Neurological Disorders ..... 405
      Gene therapy for Injuries to the Nervous System ......... 405
   Gene Therapy of Neurodegenerative Disorders ................ 406
      Vectors for Gene Therapy of Neurodegenerative 
      Disorders ............................................... 406
   Gene Therapy for Parkinson Disease ......................... 406
      Rationale of Gene Therapy for PD ........................ 407
      Techniques of Gene Therapy for PD ....................... 408
      Ex Vivo Gene Therapy of PD Using Genetically
      Engineered Cells ........................................ 411
      Prospects of Gene Therapy for PD ........................ 413
      Clinical Trials of Gene Therapy for PD .................. 414
   Gene Therapy for Alzheimer Disease ......................... 415
      Rationale of Gene Therapy for AD ........................ 415
      Methods of Gene Therapy in AD ........................... 416
   Development of Gene Therapy for Huntington Disease ......... 417
      Encapsulated Genetically Engineered Cellular Implants
      for HD .................................................. 418
      Viral Vector Mediated Administration of Neurotrophic
      Factors for HD .......................................... 418
      Antisense Therapy for HD ................................ 418
      RNAi Therapy of HD ...................................... 419
   Gene Therapy of Amyotrophic Lateral Sclerosis .............. 419
      Gene Therapy of ALS Using Neurotrophic Factors .......... 419
      Delivery of Gene Therapy for ALS ........................ 420
      RNAi Therapy for ALS .................................... 421
   Gene Therapy of Neurogenetic Disorders ..................... 421
      Scientific Basis of Gene Therapy of Neurogenetic
      Disorders ............................................... 421
      Gene Therapy of Hereditary Metabolic Disorders .......... 422
      Gene Therapy of Lysosomal Storage Disorders ............. 427
      Limitations of the Gene Therapy of Neurogenetic
      Disorders ............................................... 432
      Gene Therapy During Pregnancy ........................... 432
      Scientific Basis for Gene Therapy of Trinucleotide
      Repeat Disorders ........................................ 433
   Gene Therapy for Muscular Dystrophy ........................ 433
      Scientific Basis of Gene Therapy for Muscular
      Dystrophies ............................................. 434
      Animal Models of Muscular Dystrophy ..................... 434
      Conventional Gene Therapy of Muscular Dystrophy ......... 435
      Types of Dystrophin Constructs .......................... 435
      Alternative Approaches to Gene Therapy .................. 436
      Cell-Based Gene Therapy for Muscular Dystrophy .......... 437
      Nonviral Vectors for DMD ................................ 439
      Viral Vectors for DMD ................................... 439
      Routes Gene Delivery for Muscular Dystrophy ............. 441
      Clinical Trials of Gene Therapy of Muscular
      Dystrophies ............................................. 443
      Concluding Remarks About Gene Therapy of Muscular
      Dystrophy ............................................... 443
   Gene Therapy of Cerebrovascular Disease .................... 444
   Technologies for Gene Therapy of Cerebrovascular
   Disease .................................................... 445
      Gene Transfer to Cerebral Blood Vessels ................. 445
      Gene Therapy for Cerebral Vasospasm ..................... 445
      Gene Therapy for Cerebral Ischemia ...................... 445
      Delivery of Gene Therapy for Stroke ..................... 447
      Gene Therapy for Prevention of Stroke by Control of
      Risk Factors ............................................ 450
      Clinical Trials of Gene Therapy for Stroke .............. 451
      Concluding Remarks and Future of Gene Therapy for
      Stroke .................................................. 451
   Gene Therapy of Glioblastoma Multiforme .................... 452
      Viral Vector-Mediated Gene Therapy of GBM ............... 452
      Oncolytic Viruses for Treatment of GBM .................. 455
      Suicide Gene Therapy: HSV-Thymidine Kinase .............. 456
      Nonviral Vectors for Gene Therapy of GBM ................ 457
      Antiangiogenic Gene Therapy ............................. 458
      Stem Cell Gene Therapy .................................. 458
      Immunogene Therapy ...................................... 459
      Suppression of Growth of GBM ............................ 460
      Vaccines for GBM ........................................ 463
      Nanobiotechnology for Improving Delivery of Gene
      Therapy ................................................. 463
      Concluding Remarks on Gene Therapy of GBM ............... 463
      Combination of Gene Therapy with Other Anticancer
      Strategies .............................................. 464
   Overview of Clinical Trials of Gene Therapy ................ 465
   Adverse Effects of Gene Therapy ............................ 465
      Adverse Effects of Viral Vectors ........................ 465
      Adenoviral Vectors ...................................... 466
      Toxicity of Lipopolysaccharides ......................... 467
      Measures to Improve Safety and Efficacy of Gene
      Therapy ................................................. 467
   Gene Therapy of Glioblastoma Multiforme .................... 468
   References ................................................. 468
13 Role of Biotechnology in Drug Delivery to the Nervous
   System ..................................................... 477
   Introduction ............................................... 477
   Historical Evolution of Drug Delivery for CNS Disorders .... 478
   The Neurovascular Unit ..................................... 478
   Passage of Substances Across the Blood-Brain Barrier ....... 480
      Receptor-Mediated Peptide and Protein Transcytosis ...... 482
      Molecular Biology of the BBB ............................ 482
      Damage to BBB Manifested as Increased Permeability ...... 484
      Strategies to Cross the BBB ............................. 486
      Use of Nanobiotechnology for Therapeutic Delivery
      Across the BBB .......................................... 496
   Delivery of Cell Therapy to the Brain ...................... 496
      Intravenous Delivery of Stem Cells ...................... 497
      Intraarterial Delivery of Stem Cells .................... 497
      Pharmacologically Active Microcarriers .................. 497
      Targeted Delivery of Engineered Cells to Specific
      Tissues via Circulation ................................. 498
      Devices for Delivery of Cell Therapy .................... 499
      Cell Encapsulation ...................................... 499
      Encapsulated Cell Biodelivery ........................... 500
      Therapeutic Applications of Encapsulated Cells in
      Neurological Disorders .................................. 500
      Implantation of Microencapulated Genetically Modified
      Cells ................................................... 501
      Ferrofluid Microcapsules for Tracking with MRI .......... 502
   Delivery of Gene Therapy to the Brain ...................... 502
   Clinical Applications of Biotechnology for CNS Drug
   Delivery ................................................... 502
      Introduction of Therapeutic Substances into the CSF ..... 503
      Osmotic Opening of the Blood-Brain Barrier .............. 503
      Intraarterial Administration of Therapeutic Substances
      for CNS Disorders ....................................... 504
      Drug Delivery to the Brain in PD ........................ 504
      Drug Delivery to the Brain in AD ........................ 504
      Drug Delivery in Epilepsy ............................... 505
      Innovative Methods of Drug Delivery for Glioblastoma
      Multiforme .............................................. 505
   References ................................................. 509
14 Vaccines for Neurological Disorders ........................ 513
   Introduction ............................................... 513
      A Brief History of Vaccines ............................. 513
   Application of Vaccines in Neurology ....................... 514
      Scientific Basis of Vaccination ......................... 514
      Indications for Vaccination ............................. 514
   Construction of Vaccines ................................... 516
      DNA Vaccines ............................................ 516
      Delivery Systems and Adjuvants for Vaccines ............. 517
   Vaccines for Infections .................................... 517
      Lyme Disease Vaccine .................................... 517
      Herpes Zoster Vaccine ................................... 517
      Cytomegalovirus Vaccine ................................. 518
      Japanese Encephalitis Vaccine ........................... 520
      Tick-Borne Encephalitis Vaccine ......................... 520
   Neuroprotective Vaccine in Neurodegenerative Disorders ..... 520
      Alzheimer Disease Vaccine ............................... 521
      Amyotrophic Lateral Sclerosis ........................... 521
   Vaccines for Miscellaneous Neurological Disorders .......... 522
      Multiple Sclerosis Vaccine .............................. 522
      Vaccines for Addiction .................................. 522
      Brain Tumor Vaccine ..................................... 523
      Central Nervous System Trauma ........................... 523
   Adverse Effects of Vaccines ................................ 524
      Precautions in Use of Vaccines .......................... 525
   References ................................................. 525
15 Biotechnology for Neuroprotection .......................... 529
   Introduction ............................................... 529
      Neuroprotection and Neuroregeneration ................... 529
      Intrinsic Neuroprotective Factors ....................... 530
      Neuroprotective Gene Expression ......................... 530
      Neurotrophic Factors .................................... 532
      Intrinsic Nonenzymatic Antioxidants ..................... 533
      Activation of Transcription Factor Nrf2 ................. 533
      Intrinsic Neuroprotective Proteins ...................... 534
      Stem Cell Factor ........................................ 537
      Role of the Immune System in Neuroprotection ............ 537
      Induction of DNA Repair Enzymes for Neuroprotection ..... 538
      Microtubule-Based Neuroprotective Response to Axonal
      Injury .................................................. 539
   Biotechnology-Based Neuroprotective Agents ................. 539
   Concluding Remarks ......................................... 539
   References ................................................. 542
16 Biotechnology in Neuroregeneration ......................... 545
   Introduction ............................................... 545
      Historical Aspects of Neuroregeneration ................. 545
   Basic Aspects of Neuroregeneration ......................... 546
      Neuroprotection and Neuroregeneration ................... 547
      Intrinsic Factors that Influence Regeneration in the
      CNS ..................................................... 547
      Causes of Lack of regeneration in the CNS ............... 547
      Role of Neurotrophic Factors in Neuronal Regeneration ... 549
      Role of Synapses in CNS Regeneration .................... 550
      Role of Neural Stem Cells in Regeneration ............... 550
      Various Factors that Influence Plasticity in the CNS .... 551
      Neurotrophic Factors and Cortical Plasticity ............ 551
   Approaches to Regeneration and Repair of the CNS ........... 551
      Bioharmaceutical Approaches to Facilitate Regeneration
      of the CNS .............................................. 552
      Role of Nanobiotechnology in Regeneration and Repair
      Following CNS Trauma .................................... 554
   Integrated Approaches to Repair and Regeneration of
   CNS Disorders .............................................. 557
      Repair Strategies for Demyelinating Diseases ............ 557
      Spinal Cord Injury ...................................... 557
      Traumatic Brain Injury .................................. 558
      Stroke .................................................. 559
   Concluding Remarks and Future Prospects .................... 559
   References ................................................. 560
17 Role of Biotechnology in Neurosurgery ...................... 563
   Introduction ............................................... 563
   Neuroprotection and Neurosurgery ........................... 563
      Neuroprotective Measures Prior to Surgery ............... 563
      Cerebral Protection During Surgery of Brain Tumors ...... 565
   Applications of Cell Therapy in Neurosurgery ............... 565
      Biotechnology Approaches to Intervertebral Disc
      Degeneration ............................................ 565
      Cell Therapy for CNS Trauma ............................. 567
   Applications of Nanobiotechnology in Neurosurgery .......... 568
      Nanomaterials for Neural Implants ....................... 569
      Mimimally Invasive Surgery Using Nanocatheters .......... 570
      Femtolaser Neurosurgery ................................. 571
      Nanoparticles as an Aid to Neurosurgery ................. 571
      Quantum Dots for Molecular Imaging in Cerebrovascular
      Disorders ............................................... 572
      Nanorobots for Neurosurgery ............................. 572
   Future Prospects of Applications of Biotechnology in
   Neurosurgery ............................................... 573
   References ................................................. 573
18 Personalized Neurology ..................................... 575
   Introduction ............................................... 575
      Role of Molecular Diagnostics in the Development
      of Personalized Medicine ................................ 576
      Integration of Diagnostics and Therapeutics ............. 577
      Role of Biomarkers in Development of Personalized
      Neurology ............................................... 577
      Role of Systems Biology in Development of Personalized
      Neurology ............................................... 578
      Role of Sequencing in Development of Personalized
      Medicine ................................................ 578
      Synthetic Biology and Development of Personalized
      Medicines ............................................... 579
   Personalized Management of Alzheimer Disease ............... 580
      Role of Molecular Diagnosis and Genomics in AD .......... 580
      Guiding Therapy of AD ................................... 584
      Assessment of Conventional Therapies for AD ............. 585
      Assessment of New Therapies for AD ...................... 586
   Personalized Management of Parkinson Disease ............... 587
      Discovery of Subgroup-Selective Drug Targets in PD ...... 588
   Personalized Management of Epilepsy ........................ 588
      Choice of the Right AED ................................. 588
      Pharmacogenetics of Epilepsy ............................ 589
      Pharmacogenomics of Epilepsy ............................ 590
      Drug Resistance in Epilepsy ............................. 591
   Future Prospects for Management of Epilepsy ................ 592
      Personalized Management of Migraine ..................... 593
      Individualization of Use of Triptans for Migraine ....... 594
      Personalized Treatment of Multiple Sclerosis ............ 594
      Personalizing Mitoxantrone Therapy of MS ................ 596
      Fusokine Method of Personalized Cell Therapy of MS ...... 596
      MBP8298 ................................................. 597
      Pharmacogenomics of IFN-Я Therapy in MS ................. 597
      T Cell-Based Personalized Vaccine for MS ................ 598
   Personalized Management of Brain Cancer .................... 599
      Role of Genetics and Genomics of GBM
      in Personalized Management .............................. 599
      Prognosis of GBM Based on Its Genetic Landscape ......... 600
      Combined Neuroimaging and DNA Microarray Analysis of
      GBM ..................................................... 601
      Multigene Predictor of Outcome in GBM ................... 601
      Companion Diagnostic for Viral Gene Therapy of Brain
      Cancer .................................................. 602
      Biosimulation Approach to Personalizing Treatment of
      GBM ..................................................... 602
      Personalized Chemotherapy of GBM ........................ 602
      Supratentorial Hemispheric Diffuse Low-Grade Gliomas .... 604
      Personalized Therapy of Oligodendroglial Tumors (OTs) ... 605
      Personalized Therapy of Medulloblastomas ................ 606
      Personalized Management of Germ Cell Brain Tumors ....... 607
   Personalized Treatment of Miscellaneous Neurological
   Disorders .................................................. 607
      Personalized Management of Stroke ....................... 607
      Narcolepsy .............................................. 608
      Chronic Fatigue Syndrome ................................ 608
   Concluding Remarks and Future Prospects .................... 608
   References ................................................. 609

Index ......................................................... 613

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