Early Animal Origin of BACE1 APP/Aβ Proteolytic Function.

ABSTRACT: Alzheimer's disease is characterized, in part, by the accumulation of β-amyloid (Aβ) in the brain. Aβ is produced via the proteolysis of APP by BACE1 and γ-secretase. Since BACE1 is the rate-limiting enzyme in the production of Aβ, and a target for therapeutics, it is of interest to know when its proteolytic function evolved and for what purpose. Here, we take a functional evolutionary approach to show that BACE1 likely evolved from a gene duplication event near the base of the animal clade and that BACE1 APP/Aβ proteolytic function evolved during early animal diversification, hundreds of millions of years before the evolution of the APP/Aβ substrate. Our examination of BACE1 APP/Aβ proteolytic function includes cnidarians, ctenophores, and choanoflagellates. The most basal BACE1 ortholog

SUBMITTER: Langeland JA 

PROVIDER: S-EPMC11117577 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature