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A primary neuronal target of calcium is the small sensor and effector protein calmodulin that, in response to calcium levels, binds to and regulates hundreds of calmodulin binding proteins. The intimate and entangled relationship between calmodulin binding proteins and all phases of Alzheimer\u2019s disease has been established, but the relationship to other neurodegenerative diseases is just beginning to be evaluated. Risk factors and hallmark proteins from Parkinson\u2019s disease (PD; SNCA, Parkin, PINK1, LRRK2, PARK7), Huntington\u2019s disease (HD; Htt, TGM1, TGM2), Lewy Body disease (LBD; TMEM175, GBA), and amyotrophic lateral sclerosis\/frontotemporal disease (ALS\/FTD; VCP, FUS, TDP-43, TBK1, C90rf72, SQSTM1, CHCHD10, SOD1) were scanned for the presence of calmodulin binding domains and, within them, appropriate binding motifs. Binding domains and motifs were identified in multiple risk proteins, some of which are involved in multiple neurodegenerative diseases. The potential calmodulin binding profiles for risk proteins involved in HD, PD, LBD, and ALS\/FTD coupled with other studies on proven binding proteins supports the central and potentially critical role for calmodulin in neurodegenerative events.<\/jats:p>","DOI":"10.3390\/cimb44110394","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T05:18:57Z","timestamp":1669094337000},"page":"5802-5814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Calmodulin Binding Domains in Critical Risk Proteins Involved in Neurodegeneration"],"prefix":"10.3390","volume":"44","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":"Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1001\/jamapsychiatry.2021.4377","article-title":"Longitudinal associations of mental disorders with dementia 30-year analysis of 1.7 million New Zealand citizens","volume":"79","author":"Milne","year":"2022","journal-title":"JAMA Psych."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"683459","DOI":"10.3389\/fcell.2021.683459","article-title":"The Ageing Brain: Molecular and Cellular Basis of Neurodegeneration","volume":"9","author":"Azam","year":"2021","journal-title":"Front. 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