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Neuroprotection - Drugs, Markets and Companies


News provided by

Reportlinker

Feb 01, 2012, 05:33 ET

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NEW YORK, Feb. 1, 2012  /PRNewswire/ -- Reportlinker.com announces that a new market research report is available in its catalogue:

Neuroprotection - Drugs, Markets and Companies

http://www.reportlinker.com/p0203546/Neuroprotection---Drugs-Markets-and-Companies.html#utm_source=prnewswire&utm_medium=pr&utm_campaign=Drug_and_Medication

This report describes the role of neuroprotection in acute disorders such as stroke and injuries of the nervous system as well as in chronic diseases such as neurodegenerative disorders because many of the underlying mechanisms of damage to neural tissues are similar in all these conditions and several products are used in more than one disorder. Over 500 products have been investigated for neuroprotective effects including those from the categories of free radical scavengers, anti-excitotoxic agents, apoptosis (programmed cell death) inhibitors, anti-inflammatory agents, neurotrophic factors, metal ion chelators, ion channel modulators and gene therapy. Some of the agents are old established pharmaceuticals whereas others are new biotechnology products.

Pathomechanisms of diseases are described with steps at which neuroprotective therapies are directed. Diseases covered include cerebrovascular disorders, traumatic brain injury, spinal cord injury, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy and ischemic optic neuropathy as well as retinal degeneration. Although anesthetics such as propofol are neuroprotective as well, neuroprotection during surgery and anesthesia is discussed with the aim of preventing and treating complications that result in CNS damage.

The report contains a profile of 131 companies that have a neuroprotective product or products along with 110 collaborations. Some of the products in development at academic institutions that do not have a commercial sponsor are also included. Although an up-to-date search of the literature was performed and selected 850 references are included, a considerable amount of information has not been published anywhere else. Clinical trials of various neuroprotective agents are described and failures of trials are analyzed with suggestions for improving the selection of drugs and design of trials.The report is supplemented with 65 tables and 11 figures.

Market analysis of currently used productsthat have a neuroprotective effect are analyzed for the year 2011. Some of these products are approved for other indications but are known to have a neuroprotective effect. With the approval of new products and takeover of markets for obsolete symptomatic therapies, the neuroprotection market value will rise by the year 2016 when it will constitute a major and important component of the CNS market. Forecasts are made until 2021. By that time neuroprotection will be an established part of the neurological practice and measures will be available to achieve this effectively.

TABLE OF CONTENTS

1. Introduction 28

Definitions 28

Historical development of neuroprotection 28

Intrinsic neuroprotective factors 29

Neuroprotective gene expression 30

Upregulation of GADD34 30

Induction of NR4A proteins by CREB in neurons 31

Neurotrophic factors 31

Intrinsic nonenzymatic antioxidants 31

Activation of transcription factor Nrf2 32

Intrinsic neuroprotective proteins 32

?B-crystallin 32

Excitatory amino acid transporters 32

Extracellular serine protease thrombin 32

Galanin 33

Neuroglobin 33

Nuclear factor I-A 33

Prion protein 34

Rai adaptor protein 34

Stem cell factor 34

Role of the immune system in neuroprotection 35

Induction of DNA repair enzymes for neuroprotection 35

Pathomechanisms of CNS injury as basis for neuroprotection 36

Biomarkers of neurological disorders and neuroprotection 36

CNS biomarker identification using proteomics 36

Brain imaging for detection of biomarkers 37

Role of neuroprotection in various neurological disorders 37

Neuroprotection and neuroregeneration 38

Acute versus chronic neuroprotection 38

Discovery and evaluation of neuroprotective agents 39

Neuroprotective drug discovery 39

Discovery of CNS drugs that penetrate the blood-brain barrier 40

In vitro assays for the evaluation of neuroprotective agents 40

Oxidative injury model to test neuroprotective drugs 40

Apoptosis model for designing neuroprotective drugs 41

Transgenic mouse models of neurological disorders 41

Evaluating effects of neuroprotective drugs on living brain slices 41

Role of brain imaging in neuroprotective drug discovery and development 42

Positron emission tomography 42

Role of single photon emission computed tomography 42

Functional CT scanning to evaluate cerebrovascular protection 43

Magnetic resonance imaging for the evaluation of neuroprotectives 43

Application of nanotechnology to neuroprotection 44

Evaluation criteria for potential neuroprotective agents 44

2. Neuroprotective Agents 45

Classification of neuroprotective agents 45

Activated protein C 49

Activity-dependent neuroprotective protein 49

Adenosine analogs 50

Propentofylline 50

Antidepressants 51

Antidepressant-induced neurogenesis 51

Neurogenesis induced by electroconvulsive therapy 51

Neuroprotective effect of selective serotonin reuptake inhibitors 51

Antiepileptic drugs as neuroprotectives 53

Phenytoin 54

Valproic acid 54

Levetiracetam 54

Antiinflammatory agents 55

Aspirin 55

Interleukin-1 antagonists 55

COX-2 inhibitors 56

Nimesulide 56

Gold microparticles as anti-neuroinflammatory agents 56

Minocycline 57

Anti-apoptosis agents 58

Activated protein C 58

Calpain inhibitors 59

Caspase inhibitors 59

DNA binding drugs 59

Lithium 59

Olesoxime 60

Omega-3 fatty acids 60

Docosahexaenoic acid 60

Poly(ADP-ribose) polymerase inhibitors 61

Prevention of apoptosis by binding of proNGF to sortilin 61

Antioxidants/free radical scavengers 62

Free radical generation 62

Natural defenses against oxidative stress 62

Effects of oxidative damage 62

Oxidative damage and aging 62

Neuronal damage by free radicals 63

Oxidative damage and neurodegenerative disorders 63

Measures to control oxidative stress 64

Categories of therapeutic antioxidants 64

Alpha-phenyl-tert-butylnitrone 64

Coenzyme Q10 65

Dihydroergocryptine 65

Flavonoids 66

Mitochondria-targeted antioxidants 66

Nanoparticles as neuroprotective antioxidants 66

Neuroleptics as antioxidants 67

Nitrones 67

Translation of antioxidant neuroprotection from preclinical to clinical 68

Carbon monoxide and heme oxygenase 68

Cell transplants 68

Cells secreting neuroprotective substances 68

Stem cells 69

Stem cell activation for neuroprotection/regeneration by glucocorticoids 69

Cytokines 69

Erythropoietin 69

Non-erythropoietic EPO variants and mimics 71

Granulocyte colony-stimulating factor 72

Delta-opioid receptor agonists 72

FK960 72

Gene therapy 73

Glucagon-like peptide 74

Glatiramer acetate 74

Glutamate antagonists 74

Neuroprotection by scavenging blood glutamate 75

N-acylethanolamines for protection against glutamatergic excitotoxicity 76

Glutamate transporters 76

Glutamate transporter-mediated neuroprotective effect of drugs 76

Neuroprotection by targeting KAI subunit of kainate receptor 77

Glycine-proline-glutamate analogs 77

Herbal preparations 77

Flavonoid wogonin 78

Ginseng 78

Hydrogen sulfide 78

NMDA receptor ion channel complex 79

NMDA receptor antagonists 80

NMDA NR2B subunit receptor antagonists 80

Ifenprodil 80

Memantine as a neuroprotective agent 80

Magnesium 81

NAALADase inhibitors 81

Gacyclidine 81

N-alkylglycines 81

AMPA receptor modulators 82

Metabotropic glutamate receptor modulators 82

Cannabinoids 83

Dexanabinol 83

Glutathione 84

Heat shock proteins 84

Hormones 85

Estrogen and neuroprotection 85

Neuroprotective effect of estrogen receptor ligands 85

Selective estrogen receptor modulators 86

Mitochondrial mechanisms of estrogen neuroprotection 86

Insulin 87

Ion Channel modulators 87

Calcium channel blockers. 87

Ziconotide 88

Na+ channel blockers. 88

Neuroprotective potassium channel inhibitors 89

Kynurenine inhibitors 89

Leukocyte adhesion inhibitors 89

Modafinil 90

Neural regeneration protein 90

Neurite outgrowth-promoting prostaglandin compounds 91

Neuroimmunophilins 91

Cyclosporin-A 91

FK506 92

Rapamycin 92

Neurotrophic factors 93

Activity-dependent neurotrophic factor 93

Bone morphogenetic proteins 93

Brain-derived neurotrophic factor 94

Ciliary neurotrophic factor 94

Fibroblast growth factors 95

Glial cell line-derived neurotrophic factor 95

Insulin-like growth factor 96

Nerve growth factor 96

Neurotrophins 97

Osteogenic protein-1 97

Pigment epithelium-derived factor 97

Transforming growth factor-?1 98

Vascular endothelial growth factor 98

Neurotrophic factor-related neuroprotective agents 98

Amitriptyline as a TrkA and TrkB receptor agonist 98

Colivelin 98

Gambogic amide 99

Inosine 99

Meteorin 99

Oxygen-regulated protein 150 kD 100

Prosaptide 100

Siagoside 100

Small molecule activators of the Trk receptors 100

Nicotine and nicotinic receptor agonists 101

Neuroprotective effect of galantamine mediated via ?7nAChRs 101

Galantamine-induced A? clearance via ?7nAChRs 102

Nitric oxide-based neuroprotection 102

Nitric oxide synthase inhibitors 102

Nitric oxide mimetics 103

Nootropics 103

Piracetam 104

Nutraceuticals and food constituents 104

Coffee 104

Creatine 105

Curcumin/curry 105

Curcumin as a neuroprotectant in Alzheimer disease 105

Curcumin as a neuroprotectant in stroke 105

Curcumin as a neuroprotectant in multiple sclerosis 106

Mechanism of neuroprotective effect of curcumin 106

Glyceryltriacetate 106

Green tea 106

Nicotinamide 107

Resveratrol 107

Osmotic diuretics 108

Mannitol 108

Osteopontin 108

Oxygen therapeutics 109

Oxygen carriers 109

Hemoglobin-based oxygen carriers 109

Perfluorocarbons as oxygen carriers 110

Hyperbaric oxygen therapy 111

Peptides 111

C3-derived peptide for neuroprotection and neuroregeneration 111

Corticotropin-releasing hormone 111

Thyrotropin-releasing hormone 112

Vasoactive intestinal peptide 112

Pharmacological preconditioning 113

PPARs as drug targets for neuroprotection 113

Riluzole 113

Role of RNA interference in neuroprotection 114

Sigma receptor agonists as neuroprotective agents 114

SIRT group of proteins 114

Statins 115

Steroids 116

Dehydroepiandrosterone 116

HF0220 117

Sulforaphane 117

Tauroursodeoxycholic acid 117

Tetanus toxin as a neuroprotective agent 118

Thrombolytic agents as neuroprotective agents 118

Uncoupling protein 2 118

Vaccines as neuroprotectives 119

Vitamins as neuroprotective agents 119

Vitamin B12 119

Vitamin D 120

Non-pharmacological approaches to neuroprotection 120

Environmental enrichment 120

Mental training 120

Physical exercise 120

Hypothermia 121

Limitations of hypothermia 121

Hypothermic neuroprotection in hypoxia-ischemia 122

Hibernation induced by hydrogen sulfide 122

Ketogenic diet 122

Nonpharmacological preconditioning for neuroprotection 123

Transcranial magnetic stimulation 124

Electrical fields for improvement of cerebral function in neurodegeneration 124

Neuroprotective effect of exercise 125

Hibernation and neuroprotection 125

Suspended animation and neuroprotection 126

3. Neuroprotection in Cerebrovascular Disease 127

Introduction 127

Pathophysiology of cerebral ischemia 127

Calcium overload 128

Ion channel dysfunction in stroke 128

Role of oxygen free radicals in cerebral ischemia 129

Role of nitric oxide in cerebral ischemia 129

Glutamate as a biomarker of stroke 129

Cerebral edema in stroke 129

Gene expression in response to cerebral ischemia 130

Induction of heat shock proteins in stroke 130

Role of cytokines and adhesion molecules in stroke 130

Tumor necrosis factor-? 130

Interleukin-1 and IL-6 131

Adhesion molecules 131

DNA damage and repair in cerebral ischemia 131

Role of neurotrophic factors in stroke 132

Problems requiring investigation of the role of NTFs in stroke 132

Role of Poly(ADP-ribose) polymerase (PARP) gene 132

Role of protease-activated receptor 1 133

Reperfusion injury after cerebral ischemia 133

Neuroprotection according to zones in cerebral infarction 133

Zone of ischemic infarction 133

Penumbra 134

Current management of stroke 134

Neuroprotection in stenosis of intracranial arteries 135

Neuroprotection in transient ischemic attacks 135

Neuroprotective therapies for stroke 135

?B-crystallin as a neuroprotectant in stroke 136

Acid-sensing ion channel blockers 137

AMPA receptor antagonists as neuroprotectives for stroke 137

Zonampanel 137

Antiapoptotic neuroprotectives 137

NIM811 137

Creatine as neuroprotective in stroke 138

Lithium as a neuroprotective in stroke 138

TUDCA as a neuroprotective in stroke 138

Coagulation inhibitors as neuroprotectives 138

Heparin and enoxaparin 139

Warfarin vs dabigatran 139

Apixaban 139

Antiepileptic drugs as neuroprotectives in stroke 140

Tiagabine 140

Topiramate 140

Zonisamide 140

Anti-HMGB1 monoclonal antibody 140

Antioxidant approaches 141

Carnosine as a neuroprotective in stroke 141

Dehydroascorbic acid 141

Tocotrienols 142

Uric acid 143

Antiglutamate compounds 143

MRZ 2/576 143

L-Phenylalanine 143

Arimoclomol for stroke 143

Cardiac glycosides as neuroprotectives in stroke 144

Clenbuterol 144

Cox-2 inhibitors for ischemic stroke 144

Docosahexaenoic acid for ischemic stroke 144

Estrogen for stroke 145

Extendin-4 146

Flavones for neuroprotection in stroke 146

Granulocyte-macrophage colony-stimulating factor for cerebral ischemia 147

Modulation of histamine H2-receptors 147

Inosine for stroke 147

Insulin-like growth factor-I 148

Intravenous immunoglobulin as neuroprotective in stroke 148

Ischemic preconditioning for neuroprotection in stroke 148

Ketone bodies for neuroprotection in stroke 149

Mineralocorticoid receptor blockade for neuroprotection 149

Multifunctional neuroprotective agents 149

Nasal delivery of neuroprotective agents in stroke 150

Neuroserpin as a neuroprotective in stroke 150

N-2-mercaptopropionyl glycine 150

NeuroAid 151

Neurotrophic factors as neuroprotectives for stroke 151

AX200 151

Brain-derived neurotrophic factor 151

Fibroblast growth factor 152

Glial cell line-derived neurotrophic factor 152

Insulin-like growth factor-1 152

Neuregulin-1 153

NO-based strategies for neuroprotection in cerebral ischemia 153

Perlecan domain V 154

Peroxisome proliferator-activated receptor-? agonists 154

PGE2 EP2 receptor activation 154

Pioglitazone for reduction of stroke risk in diabetes 154

Progesterone 154

Proteosome inhibitors 155

Statins for prevention and neuroprotection in stroke 155

Sildenafil 156

Src receptor blockade 156

Stroke vaccine 156

SUN N4057 157

Thrombosis inhibitors 157

Aspirin 157

Clopidogrel 157

Dipyridamole 158

Vitamin E for neuroprotection in stroke 158

Neuroprotection in reperfusion injury 158

Prevention of hemorrhage following ischemic stroke 159

Non-pharmacological neuroprotective therapies for stroke 159

Preconditioning for neuroprotection against cerebral ischemia 159

Hypothermia for neuroprotection in acute stroke 160

Hyperbaric oxygen therapy for neuroprotection in acute stroke 160

Infrared laser therapy for ischemic stroke 161

Neurostimulation of sphenopalatine ganglion 162

Neurosurgical procedures for neuroprotection in stroke 162

Neurorehabilitation in relation to neuroprotection in stroke 163

Cell therapy for stroke 163

Stem cell transplant for stroke 163

Immortalized cell grafts for stroke 164

Stimulation of instrinsic stem cells for repair of brain in stroke 164

Neuroprotective vaccines for stroke 165

Gene therapy for neuroprotection in cerebrovascular disease 165

Regulation of microRNAs for neuroprotection in cerebral ischemia 167

RNAi-based therapy for neuroprotection in stroke 167

Neuroprotective therapies for cerebral ischemia: clinical trials 167

Albumin 168

Free radical scavengers 169

DP-b99 170

Minocycline for neuroprotection in stroke 170

Perindopril 171

Failed clinical trials of neuroprotection in stroke 171

Ancrod 172

Aptiganel 173

Cerovive 173

Citicoline 174

Desmoteplase 175

Erythropoietin as a neuroprotective in stroke 176

SPD 502 176

Tirilazad mesylate 176

Selfotel 176

Lubeluzole 177

Nalmefene 177

Gavestinel 177

Nimodipine 177

Sipatrigine 178

Causes of failure of stroke trials 178

Measures for prevention of failures in stroke trials 180

Design of acute stroke trial to facilitate drug approval 181

The ideal neuroprotective agent for stroke 181

Future prospects for neuroprotection in stroke 182

4. Neuroprotection in Traumatic Brain Injury 185

Introduction 185

Cerebral hypoxia/ischemia as a complication of trauma 185

Epidemiology of TBI 185

TBI in the military 186

Pathophysiology of TBI 186

Immediate damage following TBI 187

Cerebral edema following TBI 187

Delayed damage following TBI 187

Mechanism of axonal damage after TBI 187

Role of neuroinflammation in TBI 187

Molecular events following TBI 188

BBB damage after TBI 188

Chronic traumatic encephalopathy 188

Neurocognitive sequelae of TBI 189

Changes in neurotrophic factors following TBI 190

Changes in neurotransmitters following TBI 190

Proteomics of TBI 190

Genetic influences on outcome following TBI 191

Management of TBI 191

Control of intracranial pressure and cerebral edema 192

Corticosteroids 192

Neuroprotection in TBI 193

Antiepileptic drugs for prevention of seizures and neuroprotection 194

Antioxidants 194

Barbiturates 194

?- and ?-secretase inhibitors 195

Beta blockers 195

Bradykinin B2 antagonists 195

Cell cycle inhibitors for TBI 196

COX-2 inhibitors for neuroprotection in TBI 196

Cyclosporin for neuroprotection in TBI 196

Dexanabinol for TBI 197

Erythropoietin for neuroprotection in TBI 197

Gold implants for neuroprotection in focal TBI 197

KN 38-7271 197

Levosimendan 198

Magnesium sulfate 198

Minocycline for TBI 198

Nutritional approaches to neuroprotection in TBI 198

Branched chain amino acids to ameliorate cognitive impairment in TBI 199

Creatine for neuroprotection in TBI 199

Nicotinamide for neuroprotection in TBI 200

Omega 3 fatty acids as neuroprotectives in TBI 200

Neurotrophic factors for TBI 200

Neurosteroids as neuroprotective agents for TBI 201

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NP-1 202

Nogo-A inhibitor 203

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Polyethylene glycol for neuroprotection in TBI 204

Propofol for neuroprotection in TBI 204

Rapamycin as neuroprotective in TBI 204

Simvastatin as neuroprotective in TBI 204

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Hyperbaric oxygen therapy for TBI 207

Hypothermia 207

Reduction of microglial migration after TBI 207

Deep brain stimulation for TBI 207

Prophylactic neuroprotection against TBI 208

Role of helmets in protection against TBI 208

Role of physical exercise in protection against TBI 208

Clinical trials of neuroprotective agents in TBI 209

Ongoing clinical trials in TBI 209

Failed clinical trials in TBI 210

Differences between clinical trials and studies in animal models of TBI 211

Subgroup analysis 211

Improving the clinical trial design 211

Clinical trials combining multiple treatment strategies 212

Shortening the trial time 212

Conclusions and future prospects of neuroprotection in TBI 212

5. Neuroprotection in Spinal Cord Injury 215

Introduction 215

Pathophysiology of SCI 215

Secondary mechanisms of SCI 216

Neurotrophic factor changes in SCI 217

Management of SCI 218

Pharmacological neuroprotective agents for SCI 219

4-aminopyridine 219

Antibodies as neurite growth inhibitors in SCI 219

Bacterial enzyme chondroitinase ABC 219

Docosahexaenoic acid as neuroprotective in SCI 220

Erythropoietin as a neuroprotective in SCI 220

Free radical scavengers for neuroprotection in SCI 220

Gacyclidine 221

GYKI 52466 221

Immunosuppressants as neuroprotectants in SCI 221

Interleukin-10 for neuroprotection in SCI 221

Matrix metalloproteinase inhibitors for SCI 222

Methylprednisolone 222

Minocycline as neuroprotective in SCI 222

Neurotrophic factors for neuroprotection after SCI 223

Promotion of regeneration of neurons in SCI 223

Rho pathway and Rho antagonists in SCI 224

Selenium as a neuroprotective for SCI 224

Sialidase for enhancing recovery after SCI 224

Targeting the inflammatory response for neuroprotection in SCI 225

Uric acid as neuroprotective in SCI 225

Non-pharmacological approaches to SCI 225

Hyperbaric oxygen therapy 225

Hypothermia for SCI 225

Cell therapy for SCI 226

Autoimmune T cells against CNS myelin-associated peptide 226

Fetal neural grafts for SCI 226

Olfactory-ensheathing cells for SCI 226

Oligodendrocyte precursor cells for treatment of SCI 227

Schwann cell transplants for SCI 227

Transplantation of glial cells for SCI 227

Stem cells for SCI 227

Bone marrow stem cells for SCI 227

Embryonic stem cells for SCI 228

Transplantation of induced pluripotent stem cells in SCI 228

Transplantation of MSCs for SCI 229

Transplantation of NSCs for SCI 229

Transdifferentiation of stem cells into cholinergic neurons for SCI 230

Gene therapy for SCI 230

Combined approaches to spinal cord injury 231

Discovery of new targets for neuroprotective therapies in SCI 231

Clinical trials in SCI 232

6. Neuroprotection in Neurodegenerative Disorders 233

Introduction 233

Pathomechanism of neurodegeneration 233

Dual role of ?-synuclein in neuroprotection and neurodegeneration 233

Lack of neurotrophic factors 234

Neuroinflammation in neurodegenerative disorders 234

Neurodegeneration associated with protein misfolding 234

Modulation of neurodegeneration by molecular chaperones 234

Intrabodies targeting protein misfolding in neurodegeneration 235

Targeting proteins aggregation to prevent amyloid formation 235

Tau and neurodegeneration 235

TDP-43 proteinopathy and neurodegenerative diseases 236

Role of apoptosis in neurodegenerative disorders 236

Role of glia in neurodegeneration 236

Role of metals in neurodegeneration 237

Viral infections and neurodegeneration 237

AIDS and the nervous system 237

Avian influenza as cause of neurodegeneration 238

Genetic disorders with neurodegeneration 239

Batten disease 239

Friedrich ataxia 240

Pathomechanism of FA 240

Neuroprotection in FA 240

Niemann-Pick type C disease 240

Creutzfeldt-Jakob disease 241

Approaches to neuroprotection in neurodegenerative disorders 242

Glutamate-based therapies for neurodegenerative disorders 242

Mitochondria permeability transition pore complex and neuroprotection 243

7. Neuroprotection in Parkinson Disease 245

Introduction 245

Epidemiology of Parkinson's disease 245

Pathophysiology of Parkinson's disease 245

Oxidative stress 246

Excitotoxicity 247

Asynchronous neuronal activity 247

Apoptosis 247

Role of neurotrophic factors 247

Role of misfolding proteins 247

Genetic factors in PD 248

Alteration of dopamine homeostasis 249

Neuroprotective strategies for PD based on pathomechanism 249

RNAi screening to identify neuroprotective genes in a PD model 250

Management of Parkinson's disease 251

Limitation of conventionally administered dopamine therapy 252

Treatment of dementia associated with PD 253

Neuroprotective therapy in PD 253

Neuroprotective effect of currently used drugs for PD 253

Pramipexole 253

Rasagiline mesylate 254

Ropinirole 255

Selegiline 255

Non-pharmacological strategies for neuroprotection in PD 256

Effect of exercise and environmental enrichment on PD 256

Low-calorie diet in PD 256

Development of neuroprotective therapies for PD 257

9-methyl-?-carboline 257

Adenosine AA2 receptor antagonists 257

Antiapoptotic strategies for PD 258

Calcium channel blockers for PD 258

Cell therapies for PD 258

Stem cells for PD 258

Activation of endogenous stem cells and neural precursors 259

Cogane 260

Creatine and minocycline 260

Conserved dopamine neurotrophic factor for PD 260

Free radical scavengers for neuroprotection in Parkinson's disease 261

Antioxidants 261

Melatonin 261

Tea extracts as neuroprotectives 261

Nicotine as a neuroprotective in PD 261

Gene therapy for PD 262

Implantation of genetically engineered cells 262

Gene therapy using GDNF and neurturin 263

Glutamic acid decarboxylase gene therapy 263

Parkin gene therapy 263

Concluding remarks about gene therapy for PD 264

Heat shock protein 70 264

Neuroprotective effect of leucine-rich repeat kinase-2 inhibitors 265

Neuroprotective effect of DJ-1 protein 265

Neurotrophic factors 265

Basic fibroblast growth factor for PD 265

BDNF for PD 266

GDNF for PD 266

MANF for PD 266

Neurturin for PD 267

Platelet derived growth factor 267

Clinical trials with NTFs 267

Nrf2-mediated neuroprotection in PD 268

Omega-3 polyunsaturated fatty acids 268

RAB3B overexpression 268

RNAi therapy for PD 268

Safinamide 269

Sirtuin 2 inhibitors for neuroprotection in PD 269

Statins and PD 270

Targeting Bax 270

Vitamin D for neuroprotection in PD 270

Vaccine for PD 271

Clinical trials of neuroprotection in Parkinson's disease 271

Evaluation of neuroprotective therapies for PD 273

Current status and future challenges for neuroprotection in PD 274

8. Neuroprotection in Alzheimer Disease 277

Introduction 277

Pathomechanism of Alzheimer's disease 277

Role of glutamate transport dysfunction in AD 278

Role of neurotrophic factors in the pathomechanism of AD 278

Management of Alzheimer's disease 278

Neuroprotection in Alzheimer's disease 279

Inhibition of A? formation and aggregation 280

AN-1792 280

Cadmium telluride nanoparticles prevent A? fibril formation 281

Clioquinol 281

Colostrinin 282

FKBP52 for neuroprotection from Cu toxicity in AD 282

Monoclonal antibody m266 282

Phenserine 282

Secretase inhibitors 283

Inhibition of neuroinflammation 283

Etanercept 283

Neurotrophic factors/ gene therapy 284

NGF gene therapy 284

AL-108 285

Targeting plasminogen activator inhibitor type-1 gene 285

Estrogen and AD 286

Antioxidants 286

NSAIDS 286

Memantine 286

Dimebon 287

Cerebrolysin 288

Ginko biloba 288

Tetrahydrocannabinol for neuroprotection in AD 289

Ladostigil tartrate 290

Phosphodiesterase inhibitors as neuroprotectives 290

PPAR-? agonists 290

Role of statins in reducing the risk of AD 290

Combined therapeutic approaches to AD 291

Clinical trials in AD 291

Future prospects of neuroprotection in AD 298

Mild cognitive impairment 299

Relation of MCI to AD 299

Neuroprotection in MCI 300

9. Neuroprotection in Huntington Disease 301

Introduction 301

Pathophysiology of HD 301

Management of Huntington's disease 302

Neuroprotection in Huntington's disease 303

Antipsychotic D2 and 5-HT1A antagonists 304

Caspase inhibitors 304

Clioquinol for HD 304

Creatine for stabilizing bioenergetic defects 304

Cysteamine 305

Drugs that block inappropriate calcium release from neurons 305

Enhancing protease activity for clearance of mHtt 305

Eicosapentaenoic acid 305

Free radical scavengers 306

Histone deacetylase inhibitors 306

Inhibitors of polyglutamine aggregation HD 306

Pridopidine 307

Simvastatin as a neuroprotective in HD 307

Single chain Fv antibodies 308

SIRT1 activators for neuroprotection in HD 308

SIRT2 inhibitors for neuroprotection in HD 308

Synaptic activation of NMDA receptors 309

Tetrabenazine 309

Combinatorial therapy and targeting multiple pathways in HD 309

Cell transplants 310

Neurotrophic factors and gene therapy 310

RNAi therapy for Huntington's disease 311

10. Neuroprotection in Amyotrophic Lateral Sclerosis 313

Introduction 313

Pathophysiology of ALS 313

Neuroprotective therapies for ALS 315

Activated protein C 316

AEOL 10150 317

AIMSPRO 317

Anakinra 317

Arimoclomol for ALS 318

Antisense therapy 318

Creatine for ALS 318

Ceftriaxone for ALS 318

Coenzyme Q10 for ALS 319

COX-2 inhibitors for ALS 319

Dexpramipexole 319

Diallyl trisulfide 320

Erythropoietin for ALS 320

Gene therapy for ALS 320

Glatiramer acetate 321

Insulin-like growth factor 321

Ketogenic diet for neuroprotection in ALS 322

Lenalidomide 322

Lithium for neuroprotection in ALS 323

Methylcobalamin 323

Minocycline for ALS 323

Olesoxime as neuroprotective for ALS 323

ONO-2506 for ALS 324

Riluzole 324

RNAi-based therapy for ALS 324

Sodium phenylbutyrate 325

Stem cell therapy 325

Talampanel 325

Tamoxifen 325

Vaccination for ALS caused by SOD1 mutations 326

Vascular endothelial growth factor for ALS 326

Vitamin E for ALS 326

Clinical trials of neuroprotective therapies for ALS 327

Concluding remarks and future prospects 329

11. Neuroprotection in Miscellaneous Neurological Disorders 331

Introduction 331

Age-related dementia 331

Enhancing endogenous neurotrophic support of the aging brain 331

Pharmacological approaches for treatment of age-related dementia 332

Physical exercise to prevent decline of mental function with aging 333

Vascular dementia 333

Prediction of dementia in persons with vascular risk factors 333

Management of subcortical vascular dementia 334

Dementia with Lewy bodies 335

Neuroprotection in AIDS dementia 335

Multiple system atrophy 336

Epilepsy 336

Mechanisms of neuronal damage in epilepsy 336

Strategies for neuroprotection in epilepsy 337

Control of seizures by AEDs and neuroprotection 338

Prevention of seizures by ketogenic diet 339

Cell therapy for neuroprotection in epilepsy 340

Cell therapy of posttraumatic epilepsy 340

Cell therapy for temporal lobe epilepsy 340

Cell therapy for pharmacoresistant epilepsies 341

Gene therapy for neuroprotection in epilepsy 341

Spinal and bulbar muscular atrophy 342

Spinal muscular atrophy 342

Multiple sclerosis 343

Introduction 343

Epidemiology of multiple sclerosis 343

Pathophysiology 344

Current management of multiple sclerosis 344

Specific therapies for MS based on pathomechanism 345

Neuroprotection in multiple sclerosis 345

Clinical trials of neuroprotective therapies for MS 346

Neuroprotection by control of progressive forms of multiple sclerosis 349

Neuroprotection by controlling autoimmune inflammation in the brain 349

Remyelination for neuroprotection in multiple sclerosis 350

Agents for neuroprotection in multiple sclerosis 350

Angiotensin-II inhibitors 350

Antiglutamate agents 350

Antioxidants for neuroprotection in MS 350

Antisense and RNAi approaches to MS 351

Cell therapy for multiple sclerosis 351

Cladribine 353

Dalfampridine in MS 354

Dimethyl fumarate 354

DNA vaccine for MS 354

Erythropoietin as a neuroprotective in MS 355

Fingolimod (FTY720) 355

Fusokine composed of GM-CSF and IL-15 for immune suppression 356

Gene therapy for MS 356

Ibudilast for MS 356

IVIG for MS 357

Kinase inhibitors 357

Laquinimod 357

Monoclonal antibodies for MS 357

Natalizumab 358

Natural human antibodies for repair of myelin 358

Neurotrophic factors for multiple sclerosis 359

Oral immunomodulatory agents for MS 360

Recombinant T-cell ligands 360

Statins for MS 360

Teriflunomide 361

Concluding remarks on neuroprotection in MS 361

Neuroprotection in transverse myelitis 361

Neuroprotection in decompression sickness 362

Neuroprotection in CSF circulatory disorders 363

Neuroprotection in hydrocephalus 363

Neuroprotection in normal pressure hydrocephalus 363

Neuroprotection in infections of the CNS 364

Neuroprotection in bacterial meningitis 364

Mechanism of neural injury in bacterial meningitis 364

Strategies for neuroprotection 365

Neuroprotection in cryptococcal meningitis 365

Neuroprotective approach to rabies 365

Neuroprotection in cerebral malaria 366

Neuroprotection in hypertensive encephalopathy 366

Neuroprotection in toxic encephalopathies 367

Hepatic encephalopathy 367

Management of hepatic encephalopathy 367

Encephalopathy due to organophosphorus poisoning 368

Neuroprotection against chemotherapy-induced brain damage 368

Neuroprotection against alcohol 369

Alcoholic neurologic disorders 369

Fetal alcohol syndrome 369

Pathogenesis of alcohol-induced damage to the nervous system 369

Neuroprotection against neurotoxicity of alcohol 370

Neuroprotection against radiation encephalopathy 370

Neuroprotection in hypoxia-ischemia 371

Neuroprotection in neonatal hypoxic-ischemic brain injury 371

Minocycline for neonatal hypoxia-ischemia 372

Nicotinamide mononucleotide adenylyl transferase 1 372

Nitric oxide inhalation for neonatal hypoxia-ischemia 372

Plasminogen activator inhibitor-1 for neonatal hypoxia-ischemia 373

Recombinant erythropoietin for neonatal hypoxia-ischemia 373

Neuroprotection in carbon monoxide poisoning 373

Pathomechanism of CO poisoning as a basis for neuroprotection 373

Management of CO poisoning 374

Syndrome of delayed post-hypoxic leukoencephalopathy 375

Neuroprotection of the fetus 375

Neuroprotection in sleep apnea 375

Neuroprote

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