{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T09:31:44Z","timestamp":1776331904896,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Calmodulin (CaM) and a diversity of CaM-binding proteins (CaMBPs) are involved in the onset and progression of Alzheimer\u2019s disease (AD). In the amyloidogenic pathway, A\u03b2PP1, BACE1 and PSEN-1 are all calcium-dependent CaMBPs as are the risk factor proteins BIN1 and TREM2. Ca2+\/CaM-dependent protein kinase II (CaMKII) and calcineurin (CaN) are classic CaMBPs involved in memory and plasticity, two events impacted by AD. Coupled with these events is the production of amyloid beta monomers (A\u03b2) and oligomers (A\u03b2o). The recent revelations that A\u03b2 and A\u03b2o each bind to both CaM and to a host of A\u03b2 receptors that are also CaMBPs adds a new level of complexity to our understanding of the onset and progression of AD. Multiple A\u03b2 receptors that are proven CaMBPs (e.g., NMDAR, PMCA) are involved in calcium homeostasis an early event in AD and other neurodegenerative diseases. Other CaMBPs that are A\u03b2 receptors are AD risk factors while still others are involved in the amyloidogenic pathway. A\u03b2 binding to receptors not only serves to control CaM\u2019s ability to regulate critical proteins, but it is also implicated in A\u03b2 turnover. The complexity of the A\u03b2\/CaM\/CaMBP interactions is analyzed using two events: A\u03b2 generation and NMDAR function. The interactions between A\u03b2, CaM and CaMBPs reveals a new level of complexity to critical events associated with the onset and progression of AD and may help to explain the failure to develop successful therapeutic treatments for the disease.<\/jats:p>","DOI":"10.3390\/ijms24021393","type":"journal-article","created":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T02:06:03Z","timestamp":1673402763000},"page":"1393","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Calmodulin and Amyloid Beta as Coregulators of Critical Events during the Onset and Progression of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0163-9044","authenticated-orcid":false,"given":"Danton H.","family":"O\u2019Day","sequence":"first","affiliation":[{"name":"Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada"},{"name":"Department of Biology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,11]]},"reference":[{"key":"ref_1","first-page":"306","article-title":"The amyloid hypothesis in Alzheimer disease: New insights from new therapeutics","volume":"21","author":"Karen","year":"2022","journal-title":"Nature"},{"key":"ref_2","unstructured":"Kay, D.S., and Burrows, G.W. 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