6533b871fe1ef96bd12d220c

RESEARCH PRODUCT

Changing fate

subject

description

Abstract The alpha-secretase A disintegrin and metalloproteinase 10 (ADAM10) and the beta-secretase beta-APP cleaving enzyme 1 (BACE-1) compete in neurons to cleave the amyloid precursor protein (APP). The reaction started by BACE-1, designated the amyloidogenic pathway, leads to formation of neurotoxic amyloid beta peptides (A-betas), while alpha-secretase prevents this and gives rise to an alternative cleavage product (APPs-alpha, nonamyloidogenic pathway). The latter is also known to have neurotrophic and neuroprotective properties. Therefore, identification of mechanisms that lead to a switch in APP processing from the amyloidogenic to the nonamyloidogenic pathway is an attractive avenue in therapeutic intervention strategies regarding Alzheimer's disease. Prevention of A-beta formation by inhibiting beta-secretase BACE-1 and also by enhancement of the alternative enzyme—the alpha-secretase—or combinations of both might represent springboards for successful therapy. Here, we sum up knowledge about starting points for such therapeutic strategies on each level of cell biology, starting with transcription up to localization and activity of the protein.