Alzheimer's disease (AD) is triggered by the pathophysiological cleavage of a single transmembrane glycoprotein denominated amyloid β-protein precursor (AβPP) rendering amyloid β-peptide (Aβ) that aggregates in β-sheets forming the neuritic plaques. Since AβPP is playing a key role in AD development, this review will be focused in the structure, proteolytic processing, related secretases, mutations, localization and physiological role of AβPP protein. AβPP is present in several tissues and can be spliced at different exons rendering up to ten AβPP isoforms. The most abundant isoforms are AβPP770, AβPP751 and AβPP695, being the last one the predominant isoform in neurons. Mutations in the AβPP sequence or in the secretases that cleavage AβPP determinate an early onset of AD. AβPP and the secretase activities involve in the non amyloidogenic and the amyloidogenic pathways are putative therapeutic targets in AD, but their relationships with other physiological functions can produce controversial results.
|Número de páginas||13|
|Publicación||Current Medicinal Chemistry - Central Nervous System Agents|
|Estado||Publicada - dic 2005|
|Publicado de forma externa||Sí|