title: Neural cell cycle dysregulation and central nervous system diseases.
abstract: The cell cycle is a delicately manipulated process essential for the development, differentiation, proliferation and death of cells. Inappropriate activation of cell cycle regulators is implicated in the pathophysiology of a wide range of central nervous system (CNS) diseases, including both acute damage and chronic neurodegenerative disorders. Cell cycle activation induces the dividing astrocytes and microglia to activate and proliferate in association with glial scar formation and inflammatory factor production, which play crucial roles in the development of pathology in CNS diseases. On the other hand, in terminally differentiated neurons, aberrant re-entry into the cell cycle triggers neuronal death instead of proliferation, which may be a common pathway shared by some acquired and neurodegenerative disorders, even though multiple pathways of the cell cycle machinery are involved in distinct neuronal demise in specific pathological circumstances. In this paper, we first provide a concise description of the roles of cell cycle in neural development. We then focus on how neural cell cycle dysregulation is related to CNS diseases. Neuronal apoptosis is often detected in acute injury to the CNS such as stroke and trauma, which are usually related to the blockade of the cell cycle at the G1-S phase. In neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Niemann-Pick disease type C, however, some populations of neurons complete DNA synthesis but the cell cycle is arrested at the G2/M transition. This review summarizes advances in findings implicating cell cycle machinery in neuronal death in CNS diseases.
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China. wangwei1963@tjh.tjmu.edu.cn
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Bitao
authors.initials: B
authors.lastname: Bu
authors.forename: Minjie
authors.initials: M
authors.lastname: Xie
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Yu
authors.forename: Deding
authors.initials: D
authors.lastname: Tao
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D002493:Central Nervous System Diseases / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D009474:Neurons / Q000473:pathology* / Q000502:physiology; D015398:Signal Transduction
chemical_list: D018797:Cell Cycle Proteins