Neurochemical Mechanisms in Disease P86 pps

Index 835 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 A n -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, 36–38 836 Index 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 factor κB(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 Index 837 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 gp 91phox (Nox2), NADPH oxidase, 140 hyperglycemia, 140 nitric oxide (NO), 141 reactive oxygen species (ROS), 139 scavenging O 2 radicals, 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, 451 838 Index 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 Index 839 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 (A n )-expansion diseases, 324, 346–347 mechanisms contributing to, 348–349 and Q n -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, 111 840 Index 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 Q n -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 Index 841 β-andγ-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 5  splice 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, 645 842 Index 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 Index 843 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 APP SL /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, 113 844 Index 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 . 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. 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,. 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,