{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:27:35Z","timestamp":1791919655835,"version":"4.3.4"},"reference-count":177,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Calcium dyshomeostasis is an early critical event in neurodegeneration as exemplified by Alzheimer\u2019s (AD), Huntington\u2019s (HD) and Parkinson\u2019s (PD) diseases. Neuronal calcium homeostasis is maintained by a diversity of ion channels, buffers, calcium-binding protein effectors, and intracellular storage in the endoplasmic reticulum, mitochondria, and lysosomes. The function of these components and compartments is impacted by the toxic hallmark proteins of AD (amyloid beta and Tau), HD (huntingtin) and PD (alpha-synuclein) as well as by interactions with downstream calcium-binding proteins, especially calmodulin. Each of the toxic hallmark proteins (amyloid beta, Tau, huntingtin, and alpha-synuclein) binds to calmodulin. Multiple channels and receptors involved in calcium homeostasis and dysregulation also bind to and are regulated by calmodulin. The primary goal of this review is to show the complexity of these interactions and how they can impact research and the search for therapies. A secondary goal is to suggest that therapeutic targets downstream from calcium dyshomeostasis may offer greater opportunities for success.<\/jats:p>","DOI":"10.3390\/biom14020173","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T08:44:08Z","timestamp":1706777048000},"page":"173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The Complex Interplay between Toxic Hallmark Proteins, Calmodulin-Binding Proteins, Ion Channels, and Receptors Involved in Calcium Dyshomeostasis in Neurodegeneration"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0163-9044","authenticated-orcid":false,"given":"Danton H.","family":"O\u2019Day","sequence":"first","affiliation":[{"name":"Department of Biology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada"},{"name":"Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.bbrc.2016.07.020","article-title":"Keeping our calcium in balance to maintain our balance","volume":"483","author":"Mark","year":"2017","journal-title":"Biochem. 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