Alpha, beta-and gamma-secretases in Alzheimer's disease.
Generation of Amyloid peptide (Abeta) is at the beginning of a cascade that leads to Alzheimer's disease. Currenty, the mechanisms of Abeta generation and Abeta prevention are subject of intensive research. Amyloid precursor protein (APP), as well as beta- and gamma-secretases are the principal players involved in Abeta production, while alpha-secretase cleavage on APP prevents Abeta deposition. Inhibitors or modulators that target beta- and gamma-secretases as well as alpha-secretase activators are promising candidates for treatment of Alzheimer's disease. A deep knowledge of the secretases is required to develop disease modifying drugs that target them. The most challenging quest is to translate the growing knowledge about the cell biology of secretases and their mechanisms of action into effective therapeutics. Here, we review the main features of the secretases.
Universita degli Studi di Milano, Department of Pharmacological Sciences, Milano, Italy.
Roberta
R
Epis
Elena
E
Marcello
Fabrizio
F
Gardoni
Monica
M
Di Luca
D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D006801:Humans; D007527:Isoenzymes
D016564:Amyloid beta-Protein Precursor; D007527:Isoenzymes; D053829:Amyloid Precursor Protein Secretases