First Author | Cancino GI | Year | 2013 |
Journal | Neurobiol Aging | Volume | 34 |
Issue | 2 | Pages | 387-99 |
PubMed ID | 22592019 | Mgi Jnum | J:194439 |
Mgi Id | MGI:5473768 | Doi | 10.1016/j.neurobiolaging.2012.04.010 |
Citation | Cancino GI, et al. (2013) p73 haploinsufficiency causes tau hyperphosphorylation and tau kinase dysregulation in mouse models of aging and Alzheimer's disease. Neurobiol Aging 34(2):387-99 |
abstractText | Haploinsufficiency for the p53 family member p73 causes behavioral and neuroanatomical correlates of neurodegeneration in aging mice, including the appearance of aberrant phospho-tau-positive aggregates. Here, we show that these aggregates and tau hyperphosphorylation, as well as a generalized dysregulation of the tau kinases GSK3beta, c-Abl, and Cdk5, occur in the brains of aged p73+/- mice. To investigate whether p73 haploinsufficiency therefore represents a general risk factor for tau hyperphosphorylation during neurodegeneration, we crossed the p73+/- mice with 2 mouse models of neurodegeneration, TgCRND8+/O mice that express human mutant amyloid precursor protein, and Pin1-/- mice. We show that haploinsufficiency for p73 leads to the early appearance of phospho-tau-positive aggregates, tau hyperphosphorylation, and activation of GSK3beta, c-Abl, and Cdk5 in the brains of both of these mouse models. Moreover, p73+/-;TgCRND8+/O mice display a shortened lifespan relative to TgCRND8+/O mice that are wild type for p73. Thus, p73 is required to protect the murine brain from tau hyperphosphorylation during aging and degeneration. |