Abstract
Alzheimer’s disease, an age-related neurodegenerative disease, is characterized by several coincidental features including neuronal loss, neurofibrillary tangles and senile plaques. While the precise mechanism(s) underlying Alzheimer’s disease are incompletely understood, it is apparent that age is essential since the disease rarely strikes prior to age 55. Many other conditions such as emphysema, arthritis, and atherosclerosis also show an age-related penetrance and occur after the normal reproductive life span. This latter aspect is especially important since there is very little evolutionary pressure to maintain normal physiological relationships between biomolecules and preclude the development of these diseases. This lack of evolutionary selection allows altered or novel macromolecular relationships. Our hypothesis is that altered protein interactions and protein modifications could destabilize homeostatic relationships and/or be themselves damaging to the cellular system promoting the pathogenesis of Alzheimer’s disease and other chronic degenerative diseases.
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References
Autilio-Gambetti L, Morandi A, Tabaton M, Schaetzle B, Kovacs D, Perry G, Greenberg B, Gambetti P (1988) The amyloid precursor protein of Alz-heimer disease is expressed as a 130 kDa polypeptide in various cultured cell types. FEBS Lett 241: 94–98
Connolly JA, Kalnins VI, Cleveland DW, Kirschner MW (1977) Immunofluo-rescent staining of cytoplasmic and spindle microtubules in mouse fibro-blasts with antibody to tau protein. Proc Natl Acad Sci USA 74: 2437–2440
Canto MC, Gurney ME (1994) Development of central nervous system pathology in a murine transgenic model of human amyotrophic lateral scle-rosis. Am J Pathol 145: 1271–1279
Ellisman M, Ranganathan R, Deerinck T, Young S, Terry R, Mirra S (1987) Neuronal fibrillar cytoskeleton and endomembrane system organization in Alzheimer’s disease. In: Perry G (ed) Alteration in the neuronal cytoskele-ton in Alzheimer’s disease. Plenum, New York, pp 61–73
Galloway PG, Mulvihill P, Perry G (1992) Filaments of Lewy bodies contain insoluble cytoskeletal elements. Am J Pathol 140: 809–822
Giaccone G, Pedrotti B, Migheli A, Verga L, Perez J, Racagni G, Smith MA, Perry G, Gioia L, Selvaggini C, Salmona M, Ghiso J, Frangione B, Islam K, Bugiani O, Tagliavini F (1996)13PP and tau interaction: a possible link between amyloid and neurofibrillary tangles in Alzheimer’s disease. Am J Pathol 148: 79–87
Glenner GG (1980) Amyloid deposits and amyloidosis. N Engl J Med 302: 1283–1292
Goate A, Chartier-Harlin M-C, Mullan M, Brown J, Crawford F, Fidani L, Guiffra L, Haynes A, Irving N, James L, Mant R, Newton P, Rooke K, Rogues P,Talbot C, Pericak-Vance M, Roses A, Williamson R, Rossor M, Owen M, Hardy J (1991) Segregation of a missense mutation in the amy-loid precursor protein gene with familial Alzheimer’s disease. Nature 349: 704–706
Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI (1986) Abnormal phosphorylation of the microtubule-associated protein tau in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 83: 4913–4917
Gustke N, Steiner B, Mandelkow EM, Biernat J, Meyer HE, Goedert M, Man-delkow E (1992) The Alzheimer-like phosphorylation of tau protein re-duces microtubule binding and involves Ser-Pro and Thr-Pro motifs. FEBS Lett 307: 199–205
Harman D (1956) Aging: a theory based on free radical and radiation chem-istry. J Gerontol 11: 298–300
Hunt JV, Wolff SP (1991) Oxidative glycation and free radical production: a causal mechanism of diabetic complications. Free Radic Res Commun 12–13: 115–123
Kitaguchi N, Takahashi Y, Tokushima Y, Shiojiri S, Ito H (1988) Novel pre-cursor of Alzheimer’s disease amyloid protein shows protease inhibitory activity. Nature 331: 530–532
Lasek RJ, McQuarrie IG, Brady ST (1983) Transport of cytoskeletal and so-luble proteins in neurons. In: Opiatka A, Balaban M (eds) Biological struc-tures and coupled flows. Academic, New York, pp 329–347
Lindwall G, Cole RD (1984) Phosphorylation affects the ability of tau protein to promote microtubule assembly. J Biol Chem 259: 5301–5305
Miyata S, Monnier VM (1992) Immunocytochemical detection of advanced glycosylation end products in diabetic tissues using monoclonal antibody to pyrraline. J Clin Invest 89: 1102–1112
Miyata Y, Hoshi M, Nishida E, Minami Y, Sakai H (1986) Binding of microtubule-associated protein 2 and tau to the intermediate filament reassembled from neurofilament 70-kDa subunit protein. Its regulation by calmodulin. J Biol Chem 261: 13026–13030
Nixon RA (1991) Axonal transport of cytoskeletal proteins. In: Burgoyne RD (ed) The neuronal cytoskeleton. Wiley-Liss, New York, pp 283–307
Pappola MA, Omar RA, Kim KS, Robakis NK (1993) Immunohistochemical evidence of antioxidant stress in Alzheimer’s disease. Am J Pathol 140: 621–628
Perry G (1993) Neuritic plaques in Alzheimer disease originate from neurofibrillary tangles. Med Hypotheses 40: 257–258
Perry G, Stewart D, Friedman R, Manetto V, Autilio-Gambetti L, Gambetti P (1987) Filaments of Pick’s bodies contain altered cytoskeleton elements. Am J Pathol 127: 559–568
Perry G, Kawai M, Tabaton M, Onorato M, Mulvihill P, Richey P, Morandi A, Connolly J, Gambetti P (1991) Neuropil threads of Alzheimer’s disease show a marked alteration of the normal cytoskeleton. J Neurosci 11: 1748–1755
Praprotnik D, Smith MA, Richey PL, Vinters HV, Perry G (1996a) Plasma membrane fragility in dystrophic neurites in senile plaques of Alzheimer’s disease: an index of oxidative stress. Acta Neuropathol (Berl) (in press)
Praprotnik D, Smith MA, Richey PL, Vinters HV, Perry G (1996b) Filament heterogeneity within the dystrophic neurites of senile plaques suggests blockage of fast axonal transport in Alzheimer’s disease. Acta Neuropathol (Berl) 91: 1–5
Premkumar DRD, Smith MA, Richey PL, Petersen RB, Castellani R, Kutty RK, Wiggert B, Perry G, Kalaria RN (1995) Induction of heme oxygenase1 mRNA and protein in neurocortex and cerebral vessels in Alzheimer’s disease. J Neurochem 65: 1399–1402
Richey PL, Siedlak SL, Smith MA, Perry G (1995) Apolipoprotein E interaction with the neurofibrillary tangles and senile plaques in Alzheimer disease: implications for disease pathogenesis. Biochem Biophys Res Commun 208: 657–663
Sayre LM, Autilio-Gambetti L, Gambetti P (1985) Pathogenesis of experimental giant neurofilamentous axonopathies: a unified hypothesis based on chemical modification of neurofilaments. Brain Res Rev 357: 69–83
Selden SC, Pollard TD (1983) Phosphorylation of microtubule-associated pro-teins regulates their interaction with actin filaments. J Biol Chem 258: 7064–7071
Shaw G (1991) Neurofilament proteins. In: Burgoyne RD (ed) The neuronal cytoskeleton. Wiley-Liss, New York, pp 185–214
Smith MA, Taneda S, Richey PL, Miyata S, Yan S-D, Stern D, Sayre LM, Monnier VM, Perry G (1994a) Advanced Maillard reaction end products are associated with Alzheimer’s disease pathology. Proc Natl Acad Sci USA 91: 5710–5714
Smith MA, Kutty RK, Richey PL, Yan S-D, Stern D, Chader GJ, Wiggert B, Petersen RB, Perry G (1994b) Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer’s disease. Am J Pathol 145: 42–47
Smith MA, Sayre LM, Monnier VM, Perry G (1995a) Radical AGEing in Alz-heimer’s disease. Trends Neurosci 18: 172–176
Smith MA, Siedlak SL, Richey PL, Mulvihill P, Ghiso J, Frangione B, Tagliavini F, Giaccone G, Bugiani O, Praprotnik D, Kalaria RN, Perry G (1995b) Tau protein directly interacts with the amyloid I3-protein precursor: implica-tions for Alzheimer’s disease. Nature Med 1: 365–369
Smith MA, Dunbar CE, Miller EJ, Perry G (1996) Trypsin interaction with se-nile plaques of Alzheimer disease is mediated by I3-protein precursor. Mol Chem Neuropathol 27: 145–154
Smith MA, Rudnicka-Nawrot M, Richey PL, Praprotnik D, Mulvihill P, Miller CA, Sayre LM, Perry G (1995d) Carbonyl-related posttranslational modifi-cation of neurofilament protein in the neurofibrillary pathology of Alz-heimer’s disease. J Neurochem 64: 2660–2666
Sternberger LA, Sternberger NH (1983) Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neurofilaments in situ. Proc Natl Acad Sci USA 80: 6126–6130
Strittmatter WJ, Weisgraber KH, Huang DY, Dong LM, Salvesen GS, Peri-cak-Vance M, Schmechel D, Saunders AM, Goldgaber D, Roses AD (1993) Binding of human apolipoprotein E to synthetic amyloid beta pep-tide: isoform-specific effects and implications for late-onset Alzheimer dis-ease. Proc Natl Acad Sci USA 90: 8098–8102
Strittmatter WJ, Weisgraber KH, Goedert M, Saunders AM, Huang D, Corder EH, Dong LM, Jakes R, Alberts MJ, Gilbert JR, Han S-H, Hulette C, Einstein G, Schmechel DE, Pericak-Vance MA, Roses AD (1994) Hypothesis: microtubule instability and paired helical filament formation in Alzheimer disease brain are related to apolipoprotein E genotype. Exp Neurol 125: 163–171
Tabaton M, Whitehouse PJ, Perry G, Davies P, Autillio-Gambetti L, Gambetti P (1988) Alz 50 recognizes abnormal filaments in Alzheimer’s disease and progressive supranuclear palsy. Ann Neurol 24: 407–413
Trojanowski JQ, Schmidt ML, Shin R-W, Bramblett GT, Goedert M, Lee VM-Y (1993) PHFT(A68): from pathological marker to potential mediator of neuronal dysfunction and degeneration in Alzheimer’s disease. Clin Neuro-sci 1: 184–191
Vitek MP, Bhattacharya K, Glendening JM, Stopa E, Vlassara H, Bucala R, Manogue K, Cerami A (1994) Advanced glycation end products contribute to amyloidosis in Alzheimer disease. Proc Natl Acad Sci USA 91: 4766–4770
Wischik CM, Edwards PC, Harrington CR, Mukaetova-Ladinska E, Roth M (1995) A clinico-pathological view of molecular pathophysiology and pro-phylaxis of AD. Alzheimer Res 1 [Suppl 1]: 12.
Yan SD, Chen X, Schmidt AM, Brett J, Godman G, Zou YS, Scott CW, Ca-puto C, Frappier T, Smith MA, Perry G, Yen SH, Stern D (1994) Glycated tau protein in Alzheimer disease: a mechanism for induction of oxidant stress. Proc Natl Acad Sci USA 91: 7787–7791
Yan SD, Yan SF, Chen X, Fu J, Chen M, Kuppusamy P, Smith MA, Perry G, Godman GC, Nawroth P, Zweier JL, Stern D (1995) Non-enzymatically glycated tau in Alzheimer’s disease induces neuronal oxidant stress result-ing in cytokine gene expression and release of amyloid-I3 peptide. Nature Med 1: 693–699
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Smith, M.A., Perry, G. (1996). Protein Modifications and Interactions in Alzheimer’s Disease. In: Turner, J.D., Beyreuther, K., Theuring, F. (eds) Alzheimer’s Disease. Ernst Schering Research Foundation Workshop, vol 17. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-03248-0_10
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DOI: https://doi.org/10.1007/978-3-662-03248-0_10
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