title: Synaptic Actin Dysregulation, a Convergent Mechanism of Mental Disorders?
abstract: Actin polymerization governs activity-dependent modulation of excitatory synapses, including their morphology and functionality. It is clear from human genetics that neuropsychiatric and neurodevelopmental disturbances are multigenetic in nature, highlighting the need to better understand the critical neural pathways associated with these disorders and how they are altered by genetic risk alleles. One such signaling pathway that is heavily implicated by candidate genes for psychiatric and neurodevelopmental disorders are regulators of signaling to the actin cytoskeleton, suggesting that its disruption and the ensuring abnormalities of spine structures and postsynaptic complexes is a commonly affected pathway in brain disorders. This review will discuss recent experimental findings that strongly support genetic evidence linking the synaptic cytoskeleton to mental disorders, such as schizophrenia and autism spectrum disorders.
authors.affiliation: Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York 14214.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Kuseong-dong, Yuseong-ku, Daejeon 305-701, Korea.|Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Kuseong-dong, Yuseong-ku, Daejeon 305-701, Korea.
authors.forename: Eunjoon
authors.identifier: 0000-0001-5518-6584
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, and.
authors.forename: Dibyadeep
authors.identifier: 0000-0002-5415-3067
authors.initials: D
authors.lastname: Datta
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, and.
authors.forename: David A
authors.identifier: 0000-0002-3225-6778
authors.initials: DA
authors.lastname: Lewis
authors.affiliation: Departments of Cell Biology and Neurobiology, Duke University Medical School, Durham, North Carolina 27710 scott.soderling@duke.edu.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Soderling
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000473:pathology; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D049229:Dendritic Spines / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D001523:Mental Disorders / Q000378:metabolism* / Q000473:pathology; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D009435:Synaptic Transmission
chemical_list: D000199:Actins
keywords: Arp2/3; NMDA receptor; actin; autism; dendritic spine; schizophrenia