title: Alterations in G(1) to S phase cell-cycle regulators during amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of the motor neurons in the cerebral cortex, brain stem, and spinal cord. However, the mechanisms that regulate the initiation and/or progression of motor neuron loss in this disease remain enigmatic. Cell-cycle proteins and transcriptional regulators such as cyclins, cyclin-associated kinases, the retinoblastoma gene product (pRb), and E2F-1 function during cellular proliferation, differentiation, and cell death pathways. Recent data has implicated increased expression and activation of various cell-cycle proteins in neuronal cell death. We have examined the expression and subcellular distribution of G(1) to S phase cell-cycle regulators in the spinal cord, motor cortex, and sensory cortex from clinically and neuropathologically diagnosed sporadic ALS cases and age-matched controls. Our results indicate hyperphosphorylation of the retinoblastoma protein in motor neurons during ALS, concurrent with increased levels of cyclin D, and redistribution of E2F-1 into the cytoplasm of motor neurons and glia. These data suggest that G(1) to S phase activation occurs during ALS and may participate in molecular mechanisms regulating motor neuron death.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Ranganathan
authors.forename: Robert
authors.initials: R
authors.lastname: Bowser
mesh_terms: D000328:Adult; D000368:Aged; D000870:Anterior Horn Cells / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005260:Female; D016193:G1 Phase / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000473:pathology*; D016472:Motor Neuron Disease / Q000473:pathology*; D020671:Posterior Horn Cells / Q000473:pathology; D016160:Retinoblastoma Protein / Q000032:analysis; D016196:S Phase / Q000502:physiology*; D013116:Spinal Cord / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D016160:Retinoblastoma Protein; D014157:Transcription Factors