| First Author | Wetzel MK | Year | 2008 |
| Journal | Neuron | Volume | 59 |
| Issue | 5 | Pages | 708-21 |
| PubMed ID | 18786355 | Mgi Jnum | J:149874 |
| Mgi Id | MGI:3849268 | Doi | 10.1016/j.neuron.2008.07.021 |
| Citation | Wetzel MK, et al. (2008) p73 regulates neurodegeneration and phospho-tau accumulation during aging and Alzheimer's disease. Neuron 59(5):708-21 |
| abstractText | The genetic mechanisms that regulate neurodegeneration are only poorly understood. We show that the loss of one allele of the p53 family member, p73, makes mice susceptible to neurodegeneration as a consequence of aging or Alzheimer's disease (AD). Behavioral analyses demonstrated that old, but not young, p73+/- mice displayed reduced motor and cognitive function, CNS atrophy, and neuronal degeneration. Unexpectedly, brains of aged p73+/- mice demonstrated dramatic accumulations of phospho-tau (P-tau)-positive filaments. Moreover, when crossed to a mouse model of AD expressing a mutant amyloid precursor protein, brains of these mice showed neuronal degeneration and early and robust formation of tangle-like structures containing P-tau. The increase in P-tau was likely mediated by JNK; in p73+/- neurons, the activity of the p73 target JNK was enhanced, and JNK regulated P-tau levels. Thus, p73 is essential for preventing neurodegeneration, and haploinsufficiency for p73 may be a susceptibility factor for AD and other neurodegenerative disorders. |
