Table Of Content

Subject Index Autophagy, shifts in inttalysosomal pH dur¬ nant lysosomal processing, role of, in ing, 83 Alzheimer’s disease, 145-146 Acetylcholinesterase, 170 Band-3, 181-183 Acid hydrolases, genetic defects in, 65 Blood vessel walls, proteins in, 246 Acute phase response, 161 Body temperature, protein synthesis rates Aging efieaed by change in, 22 cellular, lipofuscin and, 66 Brain protease inhibition and, 89 human, Kunitz-type serine inhibitors and, protein changes in, 20 244 Alzheimer’s disease monkey familial, 139 age-related diseases and, 89 heterogeneous disorder of, 139 screening of, for enzymes, 175 lysosomal system and {see also Aberrant lyso¬ rat somal processing), 66 age-related diseases and, 89 neuFodegeneration in, by excitotoxicity, clipsin-like proteases in, 162 197-200 protein turnover rates in, 16 Amino acid incorporation, 17 tissue slices in, 19 Amino terminus of amyloid /3 protein precur¬ Brefeldin A sor fragment, 139-140 addidon of, during labelling period, 106 Ammonium chloride, treatment of transfected treatment of PC12 cells with, 208 Chinese hamster ovary cells by, 108 Amyloid /3 protein precursor, proteolytic cleav¬ C-Fos, hydrolyzadon of, by calpains, 224 age of, 138-139 c-Jun, hydrolyzadon of, by calfrains, 224 Amyloid precursor protein Calcium, procalpain translocated by, 222 amyloidogenic degradation of, 180 Calcium-acdvated serine protease, monkey expression of, in COS cells, 54, 131 brain containing, 175 lysosomal system in processing of, 66 Calcium-binding proteins, aedvides and struc¬ Amyloid prectirsor protein secretase tures of, 218 cleavage of full-length amyloid precursor Calcium/calmodulin-dependent protein kinase protein by, 118 11,204 direct phosphorylation of, 206 Calcium ionophore, aedvadon of calpain and, normal processing of amyloid precursor pro¬ 221 tein by, 10 Calpain proteolytic processing occurs by, 130 calcium ions and, 218 Amyloidosis, Dutch form of cerebral hemor¬ cerebral leveb of, in aging, 20 rhage with, 167 first discovery of, 8 Angjotensin-converting enzyme, 83 Calpain I, involvement of, in excitotoxicity, a 1 -Andchymotrypsin 194-197 Alzheimer amyloid deposits and, 161 m-Calpain, 195 cleavage of pepdde inhibited by, 175 p.-Calpain, 195 Andcoagulant, protease nexin-2//3-amyloid Calpastadn, inhibidon of calpain by, 23, 224 protein precursor as, 243 Carboxyl terminus of amyloid )3 protein pre¬ Andsense-RNAs, produedon of, 224 cursor fnrgment, 139 Andthrombin, protease nexin-1 as, 244 Camidne Aprodnin, use of, as a protease inhibitor, 90 calpains aedvated by, 23 Astrocyte stelladon, reâdon of, 230-231 isovaleryl, 23 Astrocytes Cathepsin B a 1-andchymotrypsin expression and, 167 catalyzadon by, 3 cathepsin H and cathepsin G identified in, cleavage of fiill-length amyloid precursor 69 protein by, 130 glia-dedved nexin synthesized by, 237 Cathepsin D role of, in amyloidogenesis, 174 irtununocytochemical studies using, 67 253 254 ANNALS NEW YORK ACADEMY OF SCIENCES inhibition of, by pcpstatin, 2 Cysteine proteinase, cytosolic, 218 protein changes in aging and, 20 Cytoskeleton, 180 Cathepsin E, 10 Cathepsin G ^ênse bodies, dystrophic neurites con¬ clipsin-like protease/rat mast cell protease-1 taining, 77 and,164 Derivatives, carboxyl-terminal amyloid /3 pro¬ immunocytochemkal studies using, 67 tein precursor, 142 serine protease and, 175 Diacylglycerol, activity of novel protein kinase Cathepsin H C dependent on, 223 immunocytochemical studies using, 67 Dolichols, increase of, in senescent brain, 91 properties of, 3 Dutch form of cerebral hemorrhage (see Amy¬ CathefKin L loidosis) immunocytochemical studies using, 67 properties of, 3 E64C, use of, as a protease inhibitor, 90, Cathepsin S, 3 106 cDNA Endocytic pathway, inhibition of proteolysis al-antichymotryp>sin, 164 in, 208 chimeric, 55 Endocytosis, rapid, 53 Chinese hamster ovary cells transfected with, Endopeptidase, multicatalydc, 8 105 transfected, 223 Endopeptidases, classification of, 1 cDNA clones, cathepsin G antibodies and, 177 Endoplasmic reticulum Cell death, lysosomal system and, 65-66 endopeptidases of posttranslational pro¬ Cells cessing in, 5 Chinese hamster ovary, 53, 105 newly synthesized proteins in, 208 COS, 54, 131, 223 proteins integrated into, 27 endothelial, 246 Endosomal/lysosomal pathway, derivatives HeLa, 223 generated by, 143 I, 105, 108 Endosome(s) PC12, 38-50, 120 C-terminal fragments in, 113 Schwann, 237 early and late, 208 Ceroid, 65 lysosomes and, 2 Chaperone, 107 materials shuttled to lysosome by, 65 Chinese hamster ovary cell translocation of proteins within, 27 plasma membrane precursors and, 53 Endothelial cells, upregulation of ^-amyloid transfection of, 105 protein precursor in, 246 Chloroquine Enteropeptidase, 9 acid-dependent proteolysis inhibited by, 208 Entorhinal cortex, 56 addition of, during chase, 106 Enzyme PC12 cell cultures treated with, 121 endothelin<onverting, 10 use of, as a protease inhibitor, 90 interleukin<onverting, 9 Chromatolytic changes, neurons exhibiting, ubiquidn-conjugate-degrading, 8 69 Epidermal growth factor, receptors for, 53 Chromogranin B, labeling of, by radioactive sulfate, 39 Epidermal growth factor binding protein, 246 Chromosome 21, loci on, increased dosage of, Epidermal growth factor receptor, 204 139 Excitotoxicity, overview of, 193-194 Chymotrypsin, 162 Exopeptidases, classification of, 1 Clipsin, 162 Extracellular matrix, protease nexin-1 binds Coagulation factor XIa, 246 tightly to, 229 Contrapsin, 164 Cystadn A, 3-4 Fibrin, blood clot formation and, 246 Cystatin B, 3-4 Fibroblasts Cysteine protease defective 1 cell, 105 cleavage of full-length amyloid precursor human, Kunitz-type serine inhibitors and, protein by, 176 244 lysosomal, inhibiting, 83 Fodtin, hydrolysis of, 220 SUBJECT INDEX 255 Leupeptin ^Jelsolin, 181 C-terminal stub and, 107 Glial-dcrivcd nexin, neurite outgrowth stimu¬ production of nexin-2 and, 121 lated by, 229 use of, as a protease inhibitor, 90 Glucocorticoids, concentration of, 167 Lewy body, gelsolin in, 186 ^-Glucuronidase, 152 Lipofuscin Glycosaminoglycans, protease nexin-2 and, accumulation of, in the cytoplasm, 89 246 lysosomal system and, 65 Glycosylation Lysosomal protease inhibitors, cultures treated detection of, in chase, 107 with, 105 N-linked, 34 Lysosomal targeting, defective I cel fibroblasts Golgi and, 105 destruction of by brefeldin A, 107 Lysosome systtem, 151 early, 208 Lysosomes endopeptidases of posttranslational pro¬ amyloid precursor protein secretase activity cessing in, 5 in, 134-135 PC 12 cells and, 38-50 early and late, 208 translocation of proteins within, 27 effect of chloroquinc on, 121 Granule protein, platelet a, 246 endosomes and, 2 markers of, 67 Heat shock protein 70 ribonuclease A degraded within, 59 degradation of proteins and, 61 translocation of proteins within, 27 uptake of proteins into lysosomes and, 152 Hel^ cells, transcription of calpain gene in, j^âcroautophagy, 58 223 Malnutrition, brain protein content resulting Hemostasis, protease nexin-2 and, 246 from, 16 Hepsin, 9 Mannose 6-phosphate receptor, defective, 108 Hereditary cerebral hemorrhage with amy¬ Membrane proteins, oxidative injury to, by free loidosis of the Dutch-type, 212 radicals, 79 i3-Hexosaminidase A, 67 Membrane-cytoskeleton complex, 180 Huntington’s disease, lysosomal system and, 66 Membranes activation of calpain in absence of, 222 I cell disease, 108 oxidative injury to, by free radicals, 79 Immunoelectron microscopy, activation of cal¬ Meninges, 164 pain studies by, 222 Meprin A, 10 Immunoprecipitation analysis, 105 Microautophagy, 58 Inflammation, proteases expected to cause, Microglia, 165-166 166 Microtuble, transport system based on, 82 Insulinase, 8 Minigenes, 53 lnterleukin-1, upregulation of /3-amyloid pro¬ Monensin, distal Golgi function inhibited by, tein precursor by, 246 208 lnterleukin-2 receptor, 204 Mucolipidosis II, 108 Interleukins, 157 Multivesicular bodies, 150 Intracellular trafficking, phosphorylation of amyloid protein precursor and, 204- ^Jeomycin, activation of calpain and, 221 206 Neprilysin, 10 Ischemic insult, 238 Nerve growth factor, 246 Nervous system, 240-241 Jun D, hydrolyzation of, by calpains, 224 Neurite retraction, thrombin-induced, 237 Neurofilament polypeptides, calpains degrade ICexin, 6 components of, 197 Kunitz-type serine inhibitors, 243 Neurofilaments, antibodies directed against, 91 L. ion Neurolysin, 9 glia-derived nexin and, 237-238 Nexin-1 hippocampal, 238 expression of, in central nervous system, 237 256 ANNALS NEW YORK ACADEMY OF SCIENCES location of, in brain, 244 Prion encephalopathies, lysosomes and, 152 regulation of neuronal cells by, 228-234 Proenzyme, inactive, 223 Nexin-2 Protease, mast cell, 162 cellular association of, 120-121 Proteasome, 8 overexpressed amyloid precursor protein Protein(s), 8 processed into, 134 docking, 29-30 role of, as cerebral anticoagulant, 243 guanine nucleodde exchange (release), 32 Nutritional deprivation, degradation of pro¬ heat shock 70, 61, 152 teins and, 61 membrane, classihcadon of, 27 [>epdde recognidon 73, 61 ^3kadaic acid, phosphorylation of amyloid secretory, 49 precursor protein and, 204 Protein C, andcoagulant effect of, 248 Oligopcpddase Protein inserdon, 30 prolyl, 8 Protein integration, 30-31 thimet, 9 Protein kinase C Oxidative injury {see Membranes) interaction of calpain with, 222-224 phosphoryladon of amyloid precursor pro¬ Paired helical filaments, Alzheimer’s disease tein by, 204 Protein kinase inhibitors, 240 brain and, 89 Papain family, cysteine endopeptidases of, 3 Protein kinases, purified, 204 Protein phosphatases, inhibition of, by okadaic Pathway acid, 206 perforant, in rat central nervous system, 56 Protein phosphoryladon, aberrant, 204 secretory, metabolism of amyloid precursor Protein sorting, signal recognidon pardcle protein through, 83 and, 29 PC12 ceUs Protein synthesis, effect of nutddon on, 16 leup)eptin-treated, 107 Protein targeting, 29-30 phophoryladon of amyloid precursor pro¬ Protein turnover rates, 16 tein and, 206 Proteoglycans, PC12 cells and, 38-50 Pepddase Proteolysis leader, 6 limited, 225 mitochondnal intermediate, 6 lysosomal, 121 signal pepdde, 6 Pepdde recognidon protein 73, 61 ^^bophonn, 30 Peripheral nervous system, rat, 55 PECT proteins, short-lived, 224 Scrapie, 149 Phorbol ester Sccrerion, consriturive, efficiency of, 41 aedvadon of protein kinase C and, 225 Secretogranin II, labeling of, by radioactive amyloid precursor protein processing accel¬ sulfate, 39 erated by, 206 Secretory cleavage pathway, targedng of amy¬ Phosphaddylinositol, reduedon of calcium loid precursor protein molecules and, concentradon by, 220 208 Phosphaddylinositol-4, 5-bisphosphatc, 220 Secretory granules, chromogranin B in, 43 Phospholipase C, inhibidon of, by neomycin, Secretory vesicles 221 endopepddases of posttransladonal pro¬ Phospholipids, interacdon with, 219 cessing in, 5 Phosphoryladon, 188 PC12 cells and, 38-50 Plasma, heparinized, 246 Serine protease inhibitor, 237 Plasma membrane, /3-amyloid precursor pro¬ Signal pepddase, eukaryotic, 34 tein cleavage on, 53 Signal recognition pardcle, 29 Plasminogen aedvators Signal sequences, protein sorting reacdon and, effects of, on neuron, 234 28-29 urokinase and dssue, 10 Spectrin Platelets, human, Kunitz-type serine inhibitors abnormal proteolysis of, 180-181 and, 244 calpains degrade components of, 197 Polyamines, cerebral calpain aedvity increased Spermine, cerebral calpain aedvity increased by, 23 by, 23 SUBJECT INDEX 257 Staurosporine, 240 Transcription factors, effect of calpain on, 224 Stcfin A, 3-4 Transfected cells, amyloid precursor protein, Stcfin B, 3-4 106 Transgenic mice, pathologic potential of amy¬ loid precursor proteins in vivo in, 177 'X'argeting signal, putative cndocytic, 53 Translocon, 35 Tau, antibodies to, 93 Transport, axonal, in rat peripheral nervous Thrombin system, 55 activation of calpain and, 221 Tubulin, degradation of, by cathepsin D, 20 anion-binding exocite, 239 blood coagulation initiated by, 246 XT biquitin membrane-bound tubulin attacked by, 20 lysosomal system and, 151 regulation of neuronal cells by, 228-234 monoclonal antibodies to, 93-94 role of, in the nervous system, 238-239 Urokinase plasminogen activator, 234 Thrombin receptor, 239 Thrombomodulin, anticoagulant function of, 247-248 itamin E, deficiency of, 83 Index of Contributors XYbraham, C. R., 174-179 Laszlo, L., 149-160 Lowe, J., 149-160 ^ânay-Schwartz, M., 16-26 Barrett, A. J., 1-15 JSâruyama, K., 129-137 Baum, L., 180-192 Masliah, E., 180-192 BcU, L., 103-117 Mayer, R. J., 149-160 Buxbaum, J. D., 203-217 Meckelein, B., 174-179 Monard, D., 237-242 Mucke, L., 174-179 ^âporaso, G. L., 203-217 Cataldo, A. M., 65-88 Naim, A. C., 203-217 Cole, G. M., 103-117 Nelson, R. B., 161-173 Cunningham, D. D., 228-236 Nitsch, C. 237-242 Czemik, A. J., 203-217 Nixon, R. A., 65-88 Nordstedt, C., 203-217 Das, S., 161-173 Dice, J. F., 58-64 Fapastoitsis, G., 174-179 Dressier, D., 161-173 PappoUa, M. A., 118-128 Dunlop, D., 16-26 Paskevich, P. A., 65-88 Picard, E., 174-179 Estus, S., 138-148 Potter, H., 161-173 Flanagan, L., 180-192 ^lamabhadran, T. V., 203-217 Razzaboni, B. L., 174-179 Gandy, S. E., 203-217 Refolo, L. M., 118-128 Gilmore, R., 27-37 Robakis, N. K., 118-128 Golde, T. E., 138-148 Greengard, P., 203-217 Saido, T. C., 218-227 Saitoh, T., 103-117, 180-192 Grimes, M., 38-52 Sambamurd, K., 118-128 Schmaier, A. H., 243-252 Hamilton, D. J., 65-88 Shioi, J., 118-128 Hirai, S., 218-227 Siman, R., 161-173, 193-202 Hope, J., 149-160 Sisodia, S. S., 53-57 Suidan, H. S., 237-242 Ishiura, S., 129-137 Sundsmo, M., 180-192 Iverfeldt, K., 203-217 Suzuki, K., 218-227 Ivy, G. O., 89-102 Suzuki, T., 203-217 ICanaley-Andrews, L., 65-88 'I'agawa, K., 129-137 Kanemaru, K., 174-179 Truong, Q. B., 103-117 Kay, M. M. B., 180-192 Kayyali, U. S., 161-173 ^ân Nostrand, W. E., 243-252 KcUaris, K. V., 27-37 Vikramkumar, R., 180-192 KeUy, R. B., 38-52 Wagner, S. L., 243-252 Wheelock, T. R., 65-88 I/ajtha, A., 16-26 Landon, M., 149-160 Younkin, S. G., 138-148 259