Increased expression of p130 in Alzheimer disease.
A number of recent findings support the notion of mechanistic parallels between Alzheimer disease (AD) and oncogenic processes, specifically, that neurons in AD, like cancer cells, display aberrant mitotic cell cycle re-entry. However, the mechanism that drives postmitotic neurons to reenter cell cycle remains elusive. In this study, we focused on the retinoblastoma-related protein p130 in AD. p130 is a transcriptional regulator that complexes with E2F4/5 in the nucleus and suppresses genes that regulate entry into the cell cycle. Interestingly, our results show that there are increases in p130 in cytoplasm of susceptible pyramidal neurons as well as neuroglia, often surrounding senile plaques, and within Hirano bodies in AD. By marked contrast, p130 is found at background levels in non-diseased, age-matched controls. Our data suggest that, despite its upregulation, the aberrant localization of p130 to the neuronal cytoplasm facilitates neuronal cell cycle re-entry in AD.
Previll
Laura A
LA
Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA.
Crosby
Meredith E
ME
Castellani
Rudy J
RJ
Bowser
Robert
R
Perry
George
G
Smith
Mark A
MA
Zhu
Xiongwei
X
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D001923:Brain Chemistry; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000737:chemistry / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130 / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology
D016229:Amyloid beta-Peptides; D050717:Retinoblastoma-Like Protein p130