Alzheimer s disease pathogenesis

Gene Protein Location Inheritance Relevance to Alzheimer s disease pathogenesis... 

Cacabelos, R., Corzo, L., Fernandez-Novoa, L., Lombardi, V. (2004) Histamine in Alzheimer s disease pathogenesis biochemistry and functional genomics. Meth. Find. Exper. Clin. Pharmacol, 26(suppl. 2), 9-16. 

Parihar MS, Hemnani T. Alzheimer s disease pathogenesis and therapeutic interventions. / Clin Neurosci 2004 11 456-67. 

Banner, C.D. and Nixon, R.A., Eds., Proteases and Protease Inhibitors in Alzheimer s Disease Pathogenesis, New York Academy of Sciences, New York, 1992. 

Streit WJ (2004) Microglia and Alzheimer s disease pathogenesis. J Neurosci Res 77 1-8. 

Perluigi, M., R. Sultana, G. Cenini et al. Redox proteomics identification of 4-hydroxynon-enal-modified brain proteins in Alzheimer s disease Role of lipid peroxidation in Alzheimer s disease pathogenesis, 3(6), 2009 682-693. 

Duda JE, Lee VM, Trojanowski JQ. Neuropathology of synuclein aggregates. / Neurosci Res. 2000 61(2) 121-127. Parihar MS, Hemnani T. Alzheimer s disease pathogenesis and therapeutic interventions. / Clin Neurosci. 

According to the amyloid hypothesis, the A 3 peptide plays a critical role in the pathogenesis of Alzheimer s disease [1]. Major forms of A 3 produced encompass 38, 40 or 42 residues. A 342 is more prone to aggregation than A 340 and in animal models an increased A[342/ A (340 ratio results in amyloid plaque pathology even when total A 3 levels are reduced [4]. The generation of A 3 is a normal process and A 3 is present in the brains and body fluids of humans throughout life. Neuronal... 

Rizzuto R, Pozzan T (2006) Microdomains of intracellular Ca + molecular determinants and functional consequences. Physiol Rev 86 369-408 Rojo EE, Eernandez JA, Maccioni AA, Jimenez JM, Maccioni RB (2008) Neuroinflammation imphcations for the pathogenesis and molecular diagnosis of Alzheimer s disease. Arch Med Res 39 1-16... 

Rather scanty evidence exists for the participation of free radicals in Alzheimer s disease and Down s syndrome. However, more recendy, reports have appeared that suggest possible free-radical involvement in the pathogenesis of these two conditions. Zemlan et al. (1989) repotted that the activity of the free-radical scavenging enzyme, SOD, was significantly increased in fibroblast cell lines derived from familial Alzheimer s and Down s patients. They hypothesized that the elevation in SOD activity observed in the Alzheimer patients supports the theory that paired helical filaments are formed by free-radical hydroxylation of proline residues. They further su ested that SOD levels might also be increased in the brains of Alzheimer s and Down s patients, and that the increase in SOD may reflect an enhanced generation of free radicals. 

Despite the indications for involvement of free radicals in Alzheimer s disease and Down s syndrome pathogenesis summarized above, more evidence is needed to establish a role for free-radical mechanisms in these disease processes. If free radicals can be demonstrated to play a role in the pathogenesis of Alzheimer s disease and Down s syndrome, then this would set the stage for chronic therapy with antioxidants in these disease states. 

Wilson DM, Binder LI. Free fatty acids stimulate the polymerization of tau and amyloid beta peptides. In vitro evidence for a common effector of pathogenesis in Alzheimer s disease. Am J Pathol 1997 150 2181-2195. 

The study of FTDP-17 has established that dysfunction or misregulation of tau protein can cause neurodegeneration and dementia. It follows that tau protein is probably also of central importance in the pathogenesis of diseases, such as Alzheimer s disease, progressive supranuclear palsy, corticobasal degeneration and Pick s disease. This is further underlined by the fact that the aforementioned diseases are partially or completely phenocopied by cases of FTDP-17. 

New Insights into AFOF-Related Pathogenesis and Therapeutics in Alzheimer s Disease... 

Suh, Y.-H., Checler, F. (2002) Amyloid precursor protein, presenUins, and a-synuclein Molecular pathogenesis and pharmacological applications in Alzheimer s disease. Pharmacol. Rev., 54, 469-525. 

Ulery, P.G., Beers, J., Mikhailenko, I., et al. (2000) Modulation of beta-amyloid precursor protein processing by the low density lipoprotein receptor-related protein (LRP). Evidence that LRP contributes to the pathogenesis of Alzheimer s disease. J. Biol. Chem., 275, 7410-7415. 

Lashuel HA, Hartley DM, Balakhaneh D, Aggarwal A, Teichberg S, Callaway DJE. (2002) New class of inhibitors of amyloid-beta fibril formation. Implications for the mechanism of pathogenesis in Alzheimer s disease. J Biol Chem 111 42881 2890. 

Cruz JC, Tsai L-H. Cdk5 deregulation in the pathogenesis of Alzheimer s disease. Trends Mol Med 2004 10 452-8. 

Iqbal K, Swaab DF, Winblad B, Wisniewski HM. Alzheimer s disease and related disorders. Etiology, pathogenesis and therapeutics. Chichester (UK) John Wiley and Sons Ltd 1999. 

One theory of the pathogenesis of Alzheimer s disease proposes that increased production or decreased secretion of the Ap peptides leads to accumulation of these peptides. A second theory proposes that an abnormal x-protein causes the formation of intracellular neurofibrillary tangles. x-Proteins are important in the maintenance of cytoskeleton function and axonal transport of proteins. Another theory is that Ap accumulation is a precipitating factor that is followed by the development of the x-enriched tangles in the dying neurons. 

M. R. Farlow, Etiology and pathogenesis of Alzheimer s disease, Am. J. Health Syst. Pharm. 55 (Suppl. 2) (1998) S5-S10. 

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