title: Calmodulin Binding Proteins and Alzheimer's Disease.
abstract: The small, calcium-sensor protein, calmodulin, is ubiquitously expressed and central to cell function in all cell types. Here the literature linking calmodulin to Alzheimer's disease is reviewed. Several experimentally-verified calmodulin-binding proteins are involved in the formation of amyloid-β plaques including amyloid-β protein precursor, β-secretase, presenilin-1, and ADAM10. Many others possess potential calmodulin-binding domains that remain to be verified. Three calmodulin binding proteins are associated with the formation of neurofibrillary tangles: two kinases (CaMKII, CDK5) and one protein phosphatase (PP2B or calcineurin). Many of the genes recently identified by genome wide association studies and other studies encode proteins that contain putative calmodulin-binding domains but only a couple (e.g., APOE, BIN1) have been experimentally confirmed as calmodulin binding proteins. At least two receptors involved in calcium metabolism and linked to Alzheimer's disease (mAchR; NMDAR) have also been identified as calmodulin-binding proteins. In addition to this, many proteins that are involved in other cellular events intimately associated with Alzheimer's disease including calcium channel function, cholesterol metabolism, neuroinflammation, endocytosis, cell cycle events, and apoptosis have been tentatively or experimentally verified as calmodulin binding proteins. The use of calmodulin as a potential biomarker and as a therapeutic target is discussed.
authors: Department of Biology, University of Toronto at Mississauga, Mississauga, Ontario, Canada.|Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.
authors: Danton H
authors: DH
authors: O'Day
authors: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors: Kristeen
authors: K
authors: Eshak
authors: Center for Human Genetic Research, Richard B. Simches Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors: Michael A
authors: MA
authors: Myre
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D011950:Receptors, Cholinergic / Q000378:metabolism
chemical_list: D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D011950:Receptors, Cholinergic; D002118:Calcium
keywords: Alzheimer’s disease; calcium; calcium channels; calmodulin; calmodulin binding proteins; cholesterol metabolism; endocytosis; genome wide association studies; neuroinflammation