title: Cytoplasmic dynein: a key player in neurodegenerative and neurodevelopmental diseases.
abstract: Cytoplasmic dynein is the most important molecular motor driving the movement of a wide range of cargoes towards the minus ends of microtubules. As a molecular motor protein, dynein performs a variety of basic cellular functions including organelle transport and centrosome assembly. In the nervous system, dynein has been demonstrated to be responsible for axonal retrograde transport. Many studies have revealed direct or indirect evidence of dynein in neurodegenerative diseases such as amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, Alzheimer's disease, Parkinson's disease and Huntington's disease. Among them, a number of mutant proteins involved in various neurodegenerative diseases interact with dynein. Axonal transport disruption is presented as a common feature occurring in neurodegenerative diseases. Dynein heavy chain mutant mice also show features of neurodegenerative diseases. Moreover, defects of dynein-dependent processes such as autophagy or clearance of aggregation-prone proteins are found in most of these diseases. Lines of evidence have also shown that dynein is associated with neurodevelopmental diseases. In this review, we focus on dynein involvement in different neurological diseases and discuss potential underlying mechanisms.
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Chen
authors.forename: Huan
authors.initials: H
authors.lastname: Xu
authors.forename: Helen M
authors.initials: HM
authors.lastname: Cooper
authors.forename: Yaobo
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D001370:Axonal Transport; D001692:Biological Transport; D018385:Centrosome / Q000648:ultrastructure; D002607:Charcot-Marie-Tooth Disease / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry*; D002658:Developmental Disabilities / Q000378:metabolism*; D004398:Dyneins / Q000502:physiology*; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000737:chemistry; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism
chemical_list: D004398:Dyneins