Neurochemical Mechanisms in Disease P86 pps

Neurodegenerative diseases cont.Alzheimer’s disease,35–36 Neurofibrillary lesions NFLs,654 Neurofibrillary tangles NFTs,272,279 classical NFT,655 ghost tangles,655–656 pretangle stage,65

stereotaxic lesions,74

systemic lesions,74–75

Muscarinic antinociception,424

Mutations

affecting components of NF-êB

signaling,307

in apolipoprotein E, presenilin 1, and,599

APP

cause dementia,273

PS1, PS2,411

causing neuropathies of infancy,557

causing Pelizaeus– Merzbacher-like

disease,554

in CMT4B2 gene,559

in CMT4 genes,559

in Cx32 gap junction protein,558

disrupting,407

ESE and ESS,406–407

ISE and ISS,407

in FMR1 gene,325

in FRA11B,326

in GFAP,565–566

in human genome,405

on MAPT exon 10,411

An-expansion,347

null,550

in periaxin gene,558

presenilin-1 gene,309

in PSEN2,273

SMN1 gene,407

splicing, see Splicing mutation

spontaneous,347

tau gene,278

Myelin-associated glycoprotein (MAG)

MAG gene,554

Myelin-associated/oligodendrocyte basic

protein (MOBP),554

Myelination,543–544

in MAG-null mice,557

model of PMP-22 mutation,558

oligodendrocyte precursors,566–567

phosphatidylinositol 3-kinase, role in,569

Myelin basic proteins (MBP),551–553,570

Myelin disorders,540,549

Myelin lipids,557,561–562

Myelin-oligodendrocyte glycoprotein

(MOG),555

Myelin proteins,548,551,559,566

proteolipid proteins,549

structure,542

vesicular protein,553

Myoinositol to creatine ratio (mI/Cr),372

Myosin light chain kinase (MLCK),224–225

Myotonic dystrophy,409–411 CUG repeats,410 noncoding trinucleotide repeats,325 type 1 (DM1),326–327,637 type 2 (DM2),349

Myotubularin-related protein 2,559

N

NADPH oxidase,370

NAIP, see Neuronal-apoptosis-inhibitory

protein (NAIP) N-Arachidonoyl-Dopamine (NADA),474–475 National Institute of Neurological and

Communicative Diseases,672 National Institute on Aging-Reagan Institute

(NIA-RI) criteria,673

NBSCs, see Normal brain stem cells (NBSCs) NCIs, see Neuronal cytoplasmic inclusions

(NCIs)

NE, see Norepinephrine (NE)

Necrosis,18 Neural stem cells (NSC),796,804 Neuregulins (NRGs),568 Neurodegenerative disease animal models AD

human,52–53 invertebrate,62–63 perspectives,64–65 primate,63–64 rodent,53–62 ALS

animal models,77–79 human,76–77 etiological,51 HD

human,79–80 invertebrate animal models,83 primate animal models,102 rodent animal models,80–82 meticulous gene manipulations,51–52 MSA

human,73–74 primate animal models,76 rodent animal models,74–76 PD

human,65–66 nonhuman primate model,72–73 rodent animal models,66–72 primates use,50–51

use and housing,50 Neurodegenerative diseases,203–205,245 and apoptosis,34

ALS,36–38

Neurodegenerative diseases (cont.)

Alzheimer’s disease,35–36

Neurofibrillary lesions (NFLs),654

Neurofibrillary tangles (NFTs),272,279

classical NFT,655

ghost tangles,655–656

pretangle stage,654

protective role against,279

Neuronal-apoptosis-inhibitory protein

(NAIP),29

Neuronal cytoplasmic inclusions (NCIs),661

Neuronal death

apoptosis,18

necrosis,18

programmed cell death,18

Neuronal disconnection syndrome,279–281

Neuronal nicotinic acetylcholine receptors

(nAChRs),760

activation,761–762

desensitization,761–762

expression, diseases associated with

autism,767

schizophrenia,765–767

and upregulation,761–762

Neuronal nuclear inclusions (NNIs),661

Neuronal plasticity,302,304

Neuropeptides,449

neuropeptide Y (NPY),459–460

Neuropil threads (NThs),654

Neuroprotection,305,546

Neurosteroids,479–480

Neurotensin (NeT),461–462

Neurotransmitters,259,570

Neurotransmitter sodium symporter (NSS)

family,172

Neurotrophic factors,462–464

Niacin

deficiency

in corn.,114–115

pellagra,115

Parkinson’s disease,115

NIA-RI criteria, see National Institute on

Aging-Reagan Institute (NIA-RI)

criteria

Nicastrin,411

Nicotine, diseases nAChRs implicated by

therapeutic effects,770

Down syndrome,771–772

Tourette syndrome,771

NINCDS-ADRDA, see Stroke/Alzheimer’s

Disease and Related Disorders

Association (NINCDS-ADRDA)

Nitric oxide (NO),424,482–484

NNIs, see Neuronal nuclear inclusions (NNIs)

Nociceptin,454 Nocistatin,454–455 Node of Ranvier,543 Nogo proteins,556 Nogo receptor-interacting protein (LRR),556 Noladin ether,474

Noncoding trinucleotide expansion diseases,

324 Noncoding trinucleotide repeats,325 Noncontrast-enhanced computed tomography

(NECT),146 Nondopaminergic signals and cognition

in PD,265 cholinergic mechanisms,266–267 GABA and subthalamic nucleus,265–266 Nonpeptide molecules,440

Nonproline-directed protein kinases

(NPDPKs),643 Nonsense-associated skipping of remote exon

(NASRE),408–409,409 Nonsense-mediated mRNA decay (NMD),

408–409 Norepinephrine (NE),426–427 Norepinephrine transporter (NET),171 Normal brain stem cells (NBSCs),806

NPDPKs, see Nonproline-directed protein

kinases (NPDPKs)

NSC, see Neural stem cells (NSC)

Nuclear factorκB (NF-κB),298 activators and inhibitors in CNS,303

in Alzheimer disease (AD),308–309 biological role of,299–301

in brain diseases,307 domains,298

in glial cells,306

in Huntington’s disease (HD),309–310 inhibitors,297

in ischemic and traumatic brain injury, 307–308

in learning and memory,305

in multiple sclerosis,310

in neuroprotection,305–306 NF-κB/IκB complex,297

in Parkinson’s disease (PD),309 pathway

of NF-κB activation,302–303

as potential therapeutic target,311 regulating genes in CNS,304

in seizures,308 signaling in CNS, role of,303 activators,303

inhibitors,303

signaling regulation,301–303

structure,297

in synaptic transmission,304–305

Nuclear tau protein,641

Nucleotide-expansion diseases,349

Nucleotides,439–440

O

Occludin,130

Oculocerebrorenal syndrome of Lowe (OCRL)

gene responsible for,230

growth factor stimulation,230

Rac activation,230

Oculopharyngeal muscular dystrophy

(OPMD),347

6-OHDA model, PD

behavioural impairment following

6-OHDA lesions

advantage,68

motor tests,67–68

DAT and NET,66

medial forebrain bundle injection

(MFB),67

striatal injection,67

substantia nigra injection,67

Oleamide,469,476–477

N-Oleoyl-dopamine (OLDA),476–477

N-Oleoyl-ethanolamide (OEA),476–477

N-Oleyl-dopamine (OLDA),469

Oligodendrocyte-myelin glycoprotein

(OMgp),560

Oligodendrocyte precursors,566–567

Oligodendrocytes,566,569

Oligodendrocyte-specific protein,553

Oligophrenin-1 (OPHN1) protein

endophilin A1 and Rho GTPases,

interactions with,224

knock-down of,222–223

localization and function in excitatory

synapses,224

OPHN1 mutations,222

signaling,224

in tissues,222

Olivopontocerebellar atrophy (OPCA),660

OMgp mutants,560

OPCA, see Olivopontocerebellar atrophy

(OPCA)

Opioid receptor-like (ORL1) receptors,449

Opioid-related peptides,449–450

Orexins,448–449

Ouabain,440–441

Oxidative stress,343–344,609–610

during aging,615

and brain edema endothelial cell incubation, ROS, 139–140

gp91phox(Nox2), NADPH oxidase,140 hyperglycemia,140

nitric oxide (NO),141 reactive oxygen species (ROS),139 scavenging O2radicals,140 energy utilization,616 fibrillary aggregates and neurodegeneration, role in,612 and metabolism

AD progression,615 iron homeostasis,615 metals

iron and copper,617 from redox-active metals,617 and mitochondria,616

apoptotic pathways,617 cytochrome oxidases and mtDNA,617 nitrogen species (RNS),615

reactive oxygen species (ROS),615 Oxytocin (OT),391–392,441–442

P

p21-Activated kinase 3 (PAK3) actin filament depolymerizing/severing factor,224

and/or synaptic plasticity,225 CREB protein levels,226 dendritic spine morphogenesis regulation, 225

expression,227 mediated cytoskeletal signaling,224 nonsyndromic X-linked MR,224

PAK3 mutations,224 phosphorylation and activation of LIMK, 224

R421X and A367E mutations,225 stress fibers triggered by,224–225 synapse formation,225

Pain ATP, facilitatory role,440 control,444

GABA and receptors in,434 hemorphins, role in,453 models,422,439,442,446 inflammatory,463 neuropathic,463 modulation,435,480 nitroglycerin inducing,483 pathophysiology of,486 regulation,451

Pain (cont.)

serotoninergicic modulatory pathways,423

syndrome,434,460,482

threshold,429,430,432,435–436,442,

449,456,467,477

transmission,447,461

N-Palmitoyl-glycine (PalGly),469,475–476

Palmityl ethanolamide (PEA),468,475–476

Paraneoplastic neurological disorders

(PND),413

Paranode,543

Parkinson disease (PD),185,245

ATP13A2

gene function and expression,730

gene location and structure,730

genetic variation,730–731

inheritance and clinical features,

729–730

structure and mutations,731

clinical diagnostic,714

clinical manifestations,713

cognitive ERP-S in,259

delayed-response tests,258

DJ1

gene function and expression,726–727

gene location and structure,726

genetic variation,727

inheritance and clinical features,726

structure and mutations,728

etiology of,248

fontostriatal circuits,252–253

GBA

gene function and expression,732

gene location and structure,732

genetic variation,732–733

inheritance and clinical features,

731–732

structure and mutations,733

HTRA2

gene function and expression,722–723

gene location and structure,722

genetic variation,723

inheritance and clinical features,722

structure and mutations,722

human disease

description,65

monogenic mutations,65

α-synuclein,65–66

idiopathic,248

impaired memory,253–255

LRRK2

gene function and expression,718–719

gene location and structure,718

genetic variation,719 inheritance and clinical features, 717–718

structure and mutations,719 molecular progression,248 neurobiology of,248 neuropathological diagnosis Lewy bodies (LBs),714 nonhuman primate models MPTP,72–73

α-synuclein gene,73 pathological process of,247 PINK1

gene function and expression,728–729 gene location and structure,728 genetic variation,729

inheritance and clinical features,728 phosphatase and tensin (PTEN),728 structure and mutations,730 prevalence and incidence,713 PRKN

exonic deletions in,725 gene function and expression,724 gene location and structure,723 genetic variation,724–726 inheritance and clinical features,723 structure,725

retinopathy,247 rodent animal models genetic rodent,69–72 MPTP,68–69 6-OHDA,66–68 SNCA

gene function and expression,716–717 gene location and structure,716 genetic variation,717

inheritance and clinical features, 715–716

structure and mutations,715 spatial orientation in,256–257 striatal GABAergic output pathways,252

as synucleinopathy,248–249 UCHL1

gene function and expression,720 gene location and structure,720 genetic variation,721

inheritance and clinical features, 719–720

postmortmem studies,720 structure and mutations,720 Partington syndrome (PRTS),347 Pathogen-associated molecular patterns

(PAMPs),363

PCD, see Programmed cell death (PCD)

PDPK, see Proline-directed protein kinases

(PDPK)

Pedunculopomtine nucleus (PPN),265–266

Pelizaeus–Merzbacher disease (PMD),551

Peptides,441

hormones,441

Peptidyl arginine–deiminase (PAD),553

Perfusion computed tomography (PCT),

146–147

Peripheral myelin protein 22 (PMP22),

557–558

Phospholipids,565

PIDDosome

caspase-2,22

PIDD,22

RAIDD,22

Pituitary adenylate cyclase-activating

polypeptide-38 (PACAP-38),

457–458

p38 kinases,368

“Plague of Athens,”4

Platelet endothelial cell adhesion molecule-1

(PECAM-1),131

p38 mitogen-activated protein kinase

(MAPK),176

PNFA, see Progressive nonfluent aphasia

(PNFA)

PNS myelin proteins,557–559

Polyalanine (An)-expansion diseases,324,

346–347

mechanisms contributing to,348–349

and Qn-expansion diseases,347–348

Polymorphisms,256,387

Polypyrimidine tract binding protein (PTB),

407

Polypyrimidine tract (PPT),403

Potassium channels,470

PPA, see Primary progressive aphasia (PPA)

PPP2R2B gene,330

Prader–Willi Syndrome (PWS),412

Pravastatin trial,618–619

Presenilin

presenilin enhancer 2 (PEN-2),411

presenilin 1 (PS1) and 2 (PS2)

mutations,673

presenilin 1 (PS1) genes,276,411

presenilin 2 (PS2) genes,276,411

Primary demyelination,545

Primary progressive aphasia (PPA),649–650

Primate models, AD

lesioning approaches

behavioural and cognitive effects,64

forebrain cholinergic neurons, neurotoxin,63–64 pharmacological approaches cholincholinergic neurotransmission, 64

drugs, preclinical,64 spontaneous approaches cognitive function,63 nonhuman primates,63 Progesterone,480–481 Programmed cell death (PCD),18 Progressive nonfluent aphasia (PNFA),650 Progressive supranuclear palsy

clinical features duration of illness,658 onset of symptoms,658 neurochemistry and neurobiology,658–659 neuropathology,658

Proinflammatory cytokines,363 Prolactin,447–448,572 Proline-directed protein kinases (PDPK),643 Pro-opiomelanocortin (POMC),364 POMC1 gene expression,374 Protein oxidation, in AD

in AD pathogenesis, early or late event, 598–599

protein carbonyls,590–592 protein nitration,592–598 Protein zero (P0),557 Psychoses

classification,10

DISC1 locus,10

neuroregulin 1 gene (NRG-1) mutations in,

10–11 recognizing

DSM IV-TR,9 Psychostimulant addiction baclofen,181 cocaine,180 DAT,181 GABAergic system,180 neurotransmitter systems modification, 180–181

serotonin reuptake inhibitor (SSRI) fluoxetine,181

TCA desipramine,181 VMAT2, dopamine levels,180 Purkinje cell bodies,336 Pyridoxine

central nervous system,110 deficiency

dendritic arborisation,111 melatonin,111

Pyridoxine (cont.)

in pregnant rats,111–112

putrescine,111

in rats,111

tryptophan conversion,112

use,110

Pyrin domains (PYDS),366

Pyruvate dehydrogenase complex,106–107

Q

Qn-expansion diseases,330–332,336–341,

348

factors contributing to neurodegeneration,

337

axonal transport, defects in,344

caspase activity,342–343

excitotoxicity/oxidative stress,343–344

gene expression, interference with,

340–341

integration of mechanisms,344–346

mitochondrial function, interference

with,341–342

proteasome function, disrupted,

339–340

toxic protein aggregates,337–338

therapeutic strategies,346

Quaking viable (qkv) mutation,569

R

RAIDD, see RIP-associated ICH-1/CED-3

homologous protein with death

domain (RAIDD)

Reactive nitrogen species (RNS),364,590

Reactive oxygen species (ROS),364

Receptor-interacting kinase-1 (RIP1),24

Reelin,392

Rel family,297

polypeptides,301

Remyelination, in MS,545

Renin-angiotensin system (RAS),444

Retina,250,260

dopamine in visual processing,260–262

foveal retinal ganglion, antagonistic

center and,262

OCT image,261

pattern ERG PERG in,261

dopaminergic dysfunction, model of,

262–264

ganglion cells,250,252

Rett syndrome,412

RFamide neuropeptides,460–461

Rho GTPases

CYFIP/Rac/PAK and fragile X syndrome,

228–229

effector pathways,223 mental-disorder-associated GAP (MEGAP),231–232 mental retardation proteins,223 oculocerebrorenal syndrome of Lowe protein 1 (OCRL1),230–231 oligophrenin-1 (OPHN1),222–224 p21-activated kinase 3 (PAK3),224–227 regulators and effectors, mutations in,221 Rho guanine nucleotide exchange factor 6 (ARHGEF6),227–228

synaptic structure and function AMPAR activity-dependent structural plasticity,220

CaMKII activation,219 Cdc42, role in,221 EphB receptor,221 mEPSCs,219 myosin–actin interactions,220 myosin light chain (MLC),220 NMDAR-dependent spine development, 219

Rac-GEF Tiam1,219 Rac transforms,219 regulatory cycle,218 Rho kinase,220 WAVE proteins,220 Rho guanine nucleotide exchange factor 6

(ARHGEF6)

ARHGEF6 gene mutation,227 nonsyndromic X-linked MR,227 RNAi-mediated knock-down of,227–228 spine morphogenesis regulation,228 RIP-associated ICH-1/CED-3 homologous

protein with death domain (RAIDD),22

Rivastigmine treatment for AD,618 Rostroventral medulla (RVM),421 Ryanodine receptor (RyanR),334

S

SAPK family, see Stress-activated protein

kinase (SAPK) family Schizophrenia,255

Chrna7,766–767 evidence,765–766 GABAergic system in,767 Schwann cell,540,543–544,546,555,558,

571 Science and clinical medicine, contrasts

between,2 3 Second mitochondria-derived activator of

caspases (Smac),31

β- and γ-Secretase inhibitors,618–619

Seizure,273,308,335,391,412

Selective serotonin reuptake inhibitors

(SSRIs),387

Semantic dementia (SD),650

Senile plaques,673

Serotonin,386–387,428–429

Serotonin transporter (SERT),171

Serotonin transporters (5-HTT),387

Serum amyloid P component (SAP),811

Sexual hormones,480–482

Short-term memory,256

Shy–Drager syndrome (SDS),660

Smac, see Second mitochondria-derived

activator of caspases (Smac)

Smooth muscle actin (SMA),132

SND, see Striatonigral degeneration (SND)

Somatostatin (SST),447

Sphingoglycolipids,561

Spinal dorsal horn (SDH),421

Spinal muscular atrophy (SMA),407–408

Spinobulbar muscular atrophy (SBMA),332

Spinocerebellar ataxia

type 1 (SCA1),333–334,350

type 2 (SCA 2),334

type 3 (SCA 3),334–335

type 6 (SCA 6),335–336

type 7 (SCA7),336

type 8 (SCA8),328,330,413

type 10 (SCA 10),349

type 12 (SCA12),330

type 17 (SCA17),336–337

Spinorphin,454

Splicing cis-elements disruption

disorders associated with,404

branch point sequence (BPS) in

humans,405–406

ectopic AG dinucleotide,406

mutations,406–407

spinal muscular atrophy (SMA),

407–408

5splice sites, aberrations of,404–405

Splicing mechanisms, physiology,403–404

Splicing mutation,408

skipping of multiple exons,408

CHRNE exon,408–409

contiguous exons,408

remote exon,408–409

SRT, see Substrate reduction therapy (SRT)

Steroids,479

STN–GPi pathway,265

Stress-activated protein kinase (SAPK)

family,614

Stress-induced analgesia (SIA),420 Stress kinases,368–370

signal transduction pathways,369 Striatonigral degeneration (SND),660 Striatum,267–268,341,343 Stroke/Alzheimer’s Disease and Related

Disorders Association (NINCDS-ADRDA),672

Substrate reduction therapy (SRT),796 Subthalamic nucleus (STN),254 Sulfogalactosylceramide,563 Survivin,29

Susceptibility-weighted imaging (SWI),150 Sydenham’s conceptualization

of specific diseases,4 bacteriology and virology,5 6 chemical and biological refinements,5 Synaptic dysfunction in AD,279

Synaptopodin,279 Synuclein,245

T

Tachykinins,455–456 Tacrine treatment for AD,618 Tandem repeat (VNTR) polymorphisms,256 Tau protein

acid- and heat-stable protein,638 aggregation of,614,639 axonal morphology and polarity,614 cell morphology,639

CNS astrocytes and oligodendrocytes,639 3D crystal lattices,639

as diagnostic marker,661–662 expression, disturbances in,639 function of,614

microtubule organization,639 modifications

deamidation,647 glycosylation,646 oxidation,647 prolyl isomerization,647 truncation,647

ubiquitnylation,647 for neuronal formation and health,639 phosphorylation

and AD,614–615 altered intracellular trafficking/polarity,

644,646 altered proteolysis,646 axonal transport,646 microtubule binding,644 physiological and pathological functions,645

Tau protein (cont.)

physiological role of,643–644

protein kinases, role in,643

protein phosphatase,643

sites,642

posttranslational modifications of,641–646

predictable secondary structure,641

3R-tau and 4R-tau isoforms,637

domains,640

and SAPK family,614

Ser-Pro and Thr-Pro motifs,614

within somatodentritic compartment of

neurons,641

structure study,639

in synaptic dysfunction,281

tau gene,279

interactions with microtubules,637

intronic mutations,637

missense mutations,637

mutations,636

representation,638

tauopathies

Alzheimer disease (AD),651–658

corticobasalganglionic degeneration,

659–660

frontotemporal dementia (FTD),

649–651

immunohistochemical studies,648–649

multiple system atrophy (MSA),

660–661

neurodegenerative disorders with,649

phosphorylation and,636

progressive supranuclear palsy,

658–659

tau transgenic mouse models,61

as therapeutic target,662

turnover of,647

PEST sequence,648

ubiquitin-independent proteosomal

degradation,648

Taurine,436–437

Tay–Sachs disease,6

clinical patterns,7

clinical phenotype, variations in,8

enzymatic studies,7

genetic variability

HEXA gene,7 8

molecular genetic studies,7

neurochemical studies,7

neuropathological observations,7

“pseudosulfatase deficiency,”9

Tetraspanin 2,554

Thalamocortical circuitry,253–255

Thalamocortical processing,267 Theory of humors,4

Thiamine and cell metabolism/function enzyme cofactor,106–108 neural membrane compound,108 deficiency,104

deficiency-related neurological disorders Alzheimer disease (AD),105 Korsakoff’s psychosis,105 oxythiamine, pyrithiamine and amprolium,105–106

WE,105 description,104 neuronal cell death, deficiency blood-brain barrier disruption,109–110 cellular energy failure,108

NMDA receptor-mediated excitotoxic-ity,109

oxidative/nitrosative stress,109 status, diet and factors,104 structure,104

Thyrotropin-releasing hormone (TRH),

446–447 Tight junction proteins claudins,130 occludin,130 paracellular permeability,131 zona occludens,131 TNF receptor-associated factor 2 (TRAF2),24 TNFRSF1A-associated via death domain

(TRADD),23–24

α-Tocopherol (vitamin E)

brain function and neurodegeneration,117 chronic deficiency,116–117

description,116 retention and secretion,117 supplementation,117 Tolcapone,255 Toll-like receptors (TLRs),363 Tourette syndrome,771 Toxic protein aggregates,337–339

TRADD, see TNFRSF1A-associated via death

domain (TRADD) Transcription factors,341,348,376,568–569 Transferrin (Tf),570

Transforming Growth Factor-Beta (TGF-β),

366–367 Transgenic mouse models, AD APP

amyloid plaques,54–55 CAA,54

cDNA,54

mutation,β and γ-secretase site,53–54

TgCRND8,54

Thy-1.2,54

APP/ADAM,58

APP/ApoE

amyloid and tau pathology,57

Aβ42 and Aβ40,57–58

synap synaptophysin and MAP 2

staining,57

APP/BACE,57

APP/PS-1

APPSL/PS-1 knock-in,56

double,54,56

FAD,54

microglial activation and astrocyte

reactivity,56–57

tau and tau/APP

cdk-5, p35 and tau-4R,60

FTD and FTDP-17,58–59

isoforms,59

Parkinsonism,58

phosphorylate, kinase,59–60

synthetic Aβ42, NFT numbers,59

Transient receptor potential melastatin 8

(TRPM8) receptor,471

Translation factors (eIF4E),369

Tricarboxylic acid (TCA) cycle,196

Trinucleotide expansions

disease,324

in genome,324

Trinucleotide repeats,324

TRPV1 receptors,470,472

Tryptophan hydroxylase (TPH1),387

T-type calcium channels,471

Tumor necrosis factor (TNF) pathway,23–25

See also Extrinsic/receptor-mediated

pathway

Tyr-MIF Peptides,453

U

Ubiquitin–proteasome system (UPS),648

UDP-Galactose,557

Umbilical cord blood (UCB),796

Unmyelinated C-fiber activation,421

V

Variable number tandem repeat (VNTR)

DAT,178–179

SERT,179

Vascular endothelial growth factor

(VEGF),811

and angiopoietins,142–143

and neovascularization (NV),812

vasogenic edema in gliomas,812

Vasoactive intestinal peptide (VIP),458 Vasoactive intestinal polypeptide (VIPergic)

neurons,248 Vasogenic brain edema cell damage lack,133 extracellular space expansion,133 formation, MMPs role

basal lamina components degradation,138 BBB permeability,138 cerebral ischemia,139 matrix metalloproteinases,138 multiple sclerosis, and CNS infections, 138

occludin, claudin-5, and ZO-1,138–139 pharmacological blockade,139 plasminogen/plasmin system,139 proteases, lactate and acidosis,138 white matter fiber tracts,133–134 Vasopressin,442

Ventro-posterior-lateral (VPL) thalamic

nucleus,112 Verbal fluency test scores,258 Very long chain fatty acids (VLCFA),564 Vesicular glutamate transporter

(VGLUT2),205 Vesicular monoamine transporters

(VMAT),175

VGLUT2, see Vesicular glutamate transporter

(VGLUT2) Virodhamine,468 Virology,5 6 Vision and visual cognition aging and cognitive event related potentials,259

neurotransmitters and cognitive ERP-S in

PD,259–260 short-term memory for visual stimuli and spatial orientation in PD,256–258 Visual cognition,256

Visual perceptual categorization,258 Visual stimuli,256

Vitamin B1, see Thiamine Vitamin B3, see Niacin Vitamin B6, see Pyridoxine Vitamin B9, see Folic acid

Vitamin B12 cofactor and inhibition, enzyme reaction,113

cytokine production, myelinolytic TNF-α,114

deficiency,113

Vitamin B12 (cont.)

methylcobalamin/adenosyl-cobalamin,

112–113

methyl trap hypothesis,114

Vitamin B complex,104

Vitamins and vitamin deficiencies

antioxidant

ascorbic acid (vitamin C),118–120

α-tocopherol (vitamin E),116–118

carotenoids,120

cobalamin (vitamin B12)

cofactor and inhibition, enzyme

reaction,113

cytokine production, myelinolytic

TNF-α,114

deficiency,113

methylcobalamin/adenosyl-cobalamin,

112–113

methyl trap hypothesis,114

folic acid (vitamin B9)

deficiency,115–116

niacin (vitamin B3)

black tongue, corn-fed dogs,114

neurological symptoms,114–115

pellagra,115

zein,114

pyridoxine (vitamin B6)

deficiency,111–112

dendritic arborisation, deficiency,111

hypothalamus,111

melatonin,111

pathology, central nervous system,110

roles,110–111

tryptophan conversion,112

use,110

thiamine (vitaminB1)

and cell metabolism/function,106–108

deficiency,104

deficiency-related neurological

disorders,105–106

description,104

neuronal cell death, deficiency,

108–110

status, diet and factors,104

structure,104

treatment for AD,620

W

Washington Heights–Inwood Columbia Aging

Project,620

Wernicke’s encephalopathy (WE),105,110

West syndrome (WS),347

Wisconsin card sorting test (WCST),257

X

X-linked demyelinating neuropathy,558

Y

YB-1, splicing trans-factor,413 Yeast artificial chromosomes (YAC),82

Z

Zellweger syndrome,565 Zinc and zinc homeostasis assembly and disassembly of tubulin,676 blood/brain and blood/cerebrospinal fluid (CSF) barriers,674

maintenance

by metallothioneins (MT),676–677

by zinc transporter (ZnT) proteins,676, 678–679

by Zrt–Irt-like (ZIP) proteins,676–678 mediated dysfunction in oxidative phosphorylation,676 NMDA receptor channels,676 plasma transport,674 protein kinase C (PKC) signaling pathways,674

role in pathogenesis of AD,679 association with SP,680

Aβ deposition,682–683

in brain,681 cellular localization,680 CSF Zn levels,681 Mini Mental Status Examination scores,680

senile plaques study,680 Western blot analysis,681

as therapeutic target in AD,683–684 transport and sequestration brain Zn concentrations,675 cytoplasmic pool,675 membrane-bound metalloprotein,675 protein–metal complex pool,675 vesicular pool,675

zinc transporter (ZnT) family,674 Zrt-Irt (ZIP) family,674 Zinc transport (ZnT) proteins cation diffusion facilitator family,678 L-type calcium channels (LTCC),678 metal response element (MRE)

in genes,678 ZnT-1 expression,678 ZnT-2, ZnT-3 and ZnT-4 expression,679 Zrt–Irt-like (ZIP) proteins

histidine-rich intracellular loop,677 ZIP-1 mRNA,677

ZIP-5, ZIP-6 and ZIP-7,678 ZIP-2, ZIP-3 and ZIP-4 expression,677