title: Neurogranin binds α-synuclein in the human superior temporal cortex and interaction is decreased in Parkinson's disease.
abstract: Neurogranin is a calmodulin binding protein that has been implicated in learning and memory, long-term potentiation and synaptic plasticity. Neurons expressing neurogranin in the cortex degenerate in late stages of Parkinson's disease with widespread α-synuclein pathology. While analyzing neurogranin gene expression levels through rtPCR in brains of mouse models overexpressing human α-synuclein, we found levels were elevated 2.5 times when compared to nontransgenic animals. Immunohistochemistry in the cortex revealed colocalization between α-synuclein and neurogranin in mouse transgenics when compared to control mice. Coimmunoprecipitation studies in the superior temporal cortex in humans confirmed interaction between α-synuclein and neurogranin, and decreased interaction between α-synuclein and neurogranin was noticed in patients diagnosed with Parkinson's disease when compared to normal control brains. Additionally, phosphorylated neurogranin levels were also decreased in the human superior temporal cortex in patients diagnosed with Parkinson's disease and patients diagnosed with dementia with Lewy bodies. Here, we show for the first time that neurogranin binds to α-synuclein in the human cortex, and this interaction decreases in Parkinson's disease along with the phosphorylation of neurogranin, a molecular process thought to be involved in learning and memory.
authors.affiliation: Departments of Neurosciences, 9500 Gilman Drive, University of California, San Diego, La Jolla, CA 92093-0624, United States; Departments of Psychiatry, 9500 Gilman Drive, University of California, San Diego, La Jolla, CA 92093-0624, United States. Electronic address: andrew.koob@uwrf.edu.
authors.forename: Andrew O
authors.initials: AO
authors.lastname: Koob
authors.affiliation: Departments of Neurosciences, 9500 Gilman Drive, University of California, San Diego, La Jolla, CA 92093-0624, United States.
authors.forename: Gideon M
authors.initials: GM
authors.lastname: Shaked
authors.affiliation: Department of Neurology, University of Munich, Klinikum der Universität München-Großhadern, 81377 München, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bender
authors.affiliation: Departments of Neurosciences, 9500 Gilman Drive, University of California, San Diego, La Jolla, CA 92093-0624, United States.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Bisquertt
authors.affiliation: Departments of Neurosciences, 9500 Gilman Drive, University of California, San Diego, La Jolla, CA 92093-0624, United States.
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.affiliation: Departments of Neurosciences, 9500 Gilman Drive, University of California, San Diego, La Jolla, CA 92093-0624, United States; Departments of Pathology, 9500 Gilman Drive, University of California, San Diego, La Jolla, CA 92093-0624, United States. Electronic address: emasliah@ucsd.edu.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D020961:Lewy Body Disease / Q000473:pathology; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D051579:Neurogranin / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D011485:Protein Binding; D013378:Substantia Nigra / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: C497604:SNCA protein, human; C497605:Snca protein, mouse; D051844:alpha-Synuclein; D051579:Neurogranin
keywords: Calmodulin; Dementia with Lewy bodies; LTP; Neurogranin; Parkinson’s disease; α-Synuclein