Gamma-secretase inhibitors in Alzheimer’s disease therapy
Authors:
Katarína Špilovská; Jan Korábečný; Kamil Kuča; Kamil Musílek
Published in:
Čes. slov. Farm., 2012; 61, 93-100
Category:
Review Articles
Overview
Neuritic plaques, which are situated in the brain of Alzheimer’s disease (AD) patients, are composed mainly of peptides containing 40 or 42 amino acid residues known as ß-amyloid plaques (Aß). The Aß peptide is the result of the enzymatic cleavage of the amyloid precursor protein (APP). In the so-called amyloidogenic pathway, the ß-secretase enzyme releases a protein fragment (C99), which is subsequently metabolized by the enzyme γ-secretase. Monomer forms of Aß are turned into oligomer forms, which are the main cause of cellular neuronal death in AD patients. The following study is focused on γ-secretase inhibitors that can slow down the production or accumulation of pathologic Aß deposits. γ secretase inhibitors that reached different phases of clinical trials are particularly reported as well as other promising groups of these analogues.
Keywords:
Alzheimer’s disease, beta amyloid, secretase, inhibitor
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