ArticleMolecular biology and evolution2014
Asynchronous evolutionary origins of Aβ and BACE1.
Article in Molecular biology and evolution, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Molecular evolution of aspartic protease gene family in vertebrates.Scientific reports · 2026Article
- Monomeric Amyloid Peptide-induced Toxicity in Human Oligodendrocyte Cell Line and Mouse Brain Primary Mixed-glial Cell Cultures: Evidence for a Neuroprotective Effect of Neurosteroid 3α-O-allyl-allopregnanolone.Neurotoxicity research · 2024Article
- Article
- Physiological Roles of Monomeric Amyloid-β and Implications for Alzheimer's Disease Therapeutics.Experimental neurobiology · 2022Review
- Brain transcriptomes of zebrafish and mouse Alzheimer's disease knock-in models imply early disrupted energy metabolism.Disease models & mechanisms · 2022Article
- Accelerated brain aging towards transcriptional inversion in a zebrafish model of the K115fs mutation of human PSEN2.PloS one · 2020Article
- Low Evolutionary Selection Pressure in Senescence Does Not Explain the Persistence of Aβ in the Vertebrate Genome.Frontiers in aging neuroscience · 2019Review
- MicroRNA-200a-3p Mediates Neuroprotection in Alzheimer-Related Deficits and Attenuates Amyloid-Beta Overproduction and Tau HyperphosphorylationFrontiers in pharmacology · 2019Article
- Dysregulation of Neuronal Iron Homeostasis as an Alternative Unifying Effect of Mutations Causing Familial Alzheimer's Disease.Frontiers in neuroscience · 2018Article
- Article
- miR-15b represses BACE1 expression in sporadic Alzheimer's disease.Oncotarget · 2017Article
- Early Origin and Evolution of the Angelman Syndrome Ubiquitin Ligase GeneFrontiers in cellular neuroscience · 2017Review
- miR-98-5p Acts as a Target for Alzheimer's Disease by Regulating Aβ Production Through Modulating SNX6 Expression.Journal of molecular neuroscience : MN · 2016Article
- Novel drug-delivery approaches to the blood-brain barrier.Neuroscience bulletin · 2015Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Neurodegenerative plaques characteristic of Alzheimer's disease (AD) are composed of amyloid beta (Aβ) peptide, which is proteolyzed from amyloid precursor protein (APP) by β-secretase (beta-site APP cleaving enzyme [BACE1]) and γ-secretase. Although γ-secretase has essential functions across metazoans, no essential roles have been identified for BACE1 or Aβ. Because their only known function results in a disease phenotype, we sought to understand these components from an evolutionary perspective. We show that APP-like proteins are found throughout most animal taxa, but sequences homologous to Aβ are not found outside gnathostomes and the β cut site is only conserved within sarcopterygians. BACE1 enzymes, however, extend through basal chordates and as far as cnidaria. We then sought to determine whether BACE1 from a species that never evolved Aβ could proteolyze APP substrates that include Aβ. We demonstrate that BACE1 from a basal chordate is a functional ortholog that can liberate Aβ from full-length human APP, indicating BACE1 activity evolved at least 360 My before Aβ.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.