{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Langeland JA"],"funding":["National Science Foundation"],"pagination":["320"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11117577"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(5)"],"pubmed_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 "],"journal":["Biology"],"pubmed_title":["Early Animal Origin of BACE1 APP/Aβ Proteolytic Function."],"pmcid":["PMC11117577"],"funding_grant_id":["RUI 1817867"],"pubmed_authors":["Langeland JA","Moore DB","DeYoung EM","Varella RA","Aguirre A","Mwenda N","Baumann L"],"additional_accession":[]},"is_claimable":false,"name":"Early Animal Origin of BACE1 APP/Aβ Proteolytic Function.","description":"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 ","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-05-20T03:18:23.172Z","creation":"2026-05-20T03:08:09.306Z"},"accession":"S-EPMC11117577","cross_references":{"pubmed":["38785802"],"doi":["10.3390/biology13050320"]}}