Alzheimer amyloid formation

Evans KC, Berger EP, Cho CG, Weisgraber KH, Lansbury PT Jr. Apolipoprotein E is a kinetic but not a thermodynamic of amyloid formation implications for the pathogenesis and treatment of Alzheimer disease. Proc Natl Acad Sci USA 1995 92 763-767. 

The lack of zinc can also be a problem in biological systems and is responsible for disease states. For example, nitric oxide-dependent apoptosis can be induced in motor neurons by zinc-deficient SOD, and in some cases of amyotrophic lateral sclerosis, zinc-deficient SOD may participate in this type of oxidative mechanism involving nitric oxide.969 One form of hereditary human hair loss or alopecia was mapped to a specific gene and a mutation found in affected individuals. The gene encodes a single zinc finger transcription factor protein with restricted expression in the brain and skin.970 Zinc has been implicated in Alzheimer s via beta amyloid formation, and a role has been attributed for the cerebral zinc metabolism in the neuropathogenesis of Alzheimer s disease.971... 

Tjernberg, L. O., Callaway, D. J., Tjemberg, A., Hahne, S., Lilliehook, C., Terenius, L., Thyberg, J., and Nordstedt, C. (1999). A molecular model of Alzheimer amyloid beta-peptide fibril formation./ Biol. Chem. 274, 12619-12625. 

CordeU, B. (1994) [3-Amyloid formation as a potential therapeutic target for Alzheimer s disease. Annu. Rev. Pharmacol. Toxicol., 34, 69-89. 

Hu, J., Igarashi, A., Kamata, M., Nakagawa, H. (2001) Angiotensin-converting enzyme degrades Alzheimer amyloid [3-peptide (A[3) retards A[3 aggregation, deposition, fibril formation and inhibits cytotoxicity. J. Biol. Chem., 276, 47863 7868. 

Dietary intervention with crude MegaNatural-AZ grape seed extract significantly reduced (by 30-50%) Alzheimer s disease-type cognitive deterioration in mice by prevention of amyloid formation in the brain [8]. However, it is essential to determine which components of the extract exhibited bioactivity in the transgenic... 

Coppen A, Ghose K, Montgomery S, et al Continuation therapy with amitriptyline in depression. Br J Psychiatry 133 28-33, 1978 Coppen A, Swade C, Wood K Lithium restores abnormal platelet 5-HT transport in patients with affective disorders. Br J Psychiatry 136 235-238, 1980 Coppen A, Swade C, Jones SA, et al Depression and tetrahydrobiopterin the folate connection. J Affect Disord 16 103-107, 1989 Cordell B 3-Amyloid formation as a potential therapeutic target for Alzheimer s disease. Annu Rev Pharmacol Toxicol 34 69-89, 1994 Corkin S Acetylcholine, aging, and Alzheimer s disease imphcations of treatment. Trends Neurosci 4 287-290, 1981... 

FIGURE 12-38. Another current therapeutic approach to preventing the neuronal destruction in Alzheimer s disease is also based on the molecular neurobiology of beta amyloid formation but emphasizes the involvement of APO-E binding protein in this process. If the synthesis of good APO-E could be ensured or the synthesis of bad APO-E prevented, possibly amyloid would not accumulate in the neuron. Changing the deposition of beta amyloid would hopefully prevent the progressive course of Alzheimer s disease. 

Bush AI, Pettingell WH, Multhaup G, Paradis M, Vonsattel JP, Gusella JF, Beyreuther K, Masters CL, Tanzi RE. 1994. Rapid induction of Alzheimer A beta amyloid formation by zinc. Science 265 1464-1467. 

Jarrett, J.T., Berger, E.P. and Lansbury, Jr. P.T. (1993) The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation implications for the pathogenesis of Alzheimer s disease. Biochemistry 32,4693 1697. 

Bush Al, Multhaup G, Moir RD, Williamson TG, Small DH, Rumble B, Pollwein P, Beyreuther K, Masters CL (1993) A novel zinc(ll) binding site modulates the function of the beta A4 amyloid protein precursor of Alzheimer s disease. J Biol Chem 268 16109-16112 Bush Al, Pettingell WH, Multhaup G, d Paradis M, Vonsattel JP, Gusella JF, Beyreuther K, Masters CL, Tanzi RE (1994) Rapid induction of Alzheimer A beta amyloid formation by zinc. Science 265 1464-1467... 

Sunde M, et al. Common core structure of amyloid fibrils by synchrotron X-ray diffraction. J. Molec. Biol. 1997 273 729. Tjemberg LO, et al. A molecular model of Alzheimer amyloid beta -peptide fibril formation. J. Biol. Chem. 1999 274 12619-12625. Benzinger TLS, et al. Two-dimensional structure of beta-Amyloid (10-35) fibrils. Biochem. 2000 39 3491-3499. 

Luhrs T, Ritter C, Adrian M, Riek-Loher D, Bohrmann B, DobeU H, Schubert D, Riek R (2005) 3D structure of Alzheimer s amyloid-beta(1 2) fibrils. Proc Natl Acad Sci USA 102 17342-17347 Ma B, Nussinov R (2002) Molecular dynanfics simulations of alanine rich beta-sheet oligomers insight into amyloid formation. Protein Sci 11 2335-2350... 

Many mechanisms of aggregation of amyloids have been studied and provide us with the insight into ways to control amyloid formation. Among the variety of protein amyloids, p-amyloids (i.e., Ap (1-40), Ap (1-42), Ap (1-43)) have been considered critical to understanding Alzheimer s disease [27]. The plaques in brain tissue with Alzheimer s disease are predominantly comprised of two Ap amyloids, Ap (1-40) and Ap (1-42). 

Chen, Y.R. and Glabe, C.G. 2006. Distinct early folding and aggregation properties of Alzheimer amyloid-P peptides AP40 and AP42 Stable trimer or tetramer formation by AP42. J. Biol. Chem. 281 24414-24422... 

Y. Matsuzaki, K. Cholesterol-dependent formation of GMl ganglioside-bound amyloid P-protein, an endogenous seed for Alzheimer amyloid. J. Biol. Chem. 2001,276, 24985-24990. 

---