Cyclin-dependent kinases in neural development and degeneration.
There is increasing evidence suggesting that cyclin-dependent kinases (Cdks) that normally regulate cell cycle progression may also be involved in the pathogenesis of neurodegenerative disorders and in the apoptotic death of neurons subjected to various insults. Deregulation of Cdks has been observed in an increasing number of neurological disorders, including Alzheimer's and Parkinson's diseases as well as amyotrophic lateral sclerosis (ALS). Unchecked expression of these proteins can potently induce apoptotic or necrotic neuronal cell death. Cdks initiate death pathways by derepressing E2F-1/pRb-dependent transcription at neuronal G1/S checkpoint. On the contrary, deregulation of Cdk5, which is not involved in cell cycle control, contributes to neurodegeneration by altering the phosphorylation state of non-membrane-associated proteins. This review describes work indicating Cdks' roles in the nervous system and how they may cogitate in leading neurons to their demise.
Lim
Anthony C B
AC
Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Republic of Singapore. mclab30@imcb.mus.edu.sg
Qi
Robert Z
RZ
D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000235:genetics*; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D009410:Nerve Degeneration / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D014157:Transcription Factors; D018844:Cyclin-Dependent Kinases