| First Author | Huang YR | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 6 | Pages | 112624 |
| PubMed ID | 37302068 | Mgi Jnum | J:343181 |
| Mgi Id | MGI:7564375 | Doi | 10.1016/j.celrep.2023.112624 |
| Citation | Huang YR, et al. (2023) ArhGAP11A mediates amyloid-beta generation and neuropathology in an Alzheimer's disease-like mouse model. Cell Rep 42(6):112624 |
| abstractText | Amyloid-beta (Abeta) plays an important role in the neuropathology of Alzheimer's disease (AD), but some factors promoting Abeta generation and Abeta oligomer (Abetao) neurotoxicity remain unclear. We here find that the levels of ArhGAP11A, a Ras homology GTPase-activating protein, significantly increase in patients with AD and amyloid precursor protein (APP)/presenilin-1 (PS1) mice. Reducing the ArhGAP11A level in neurons not only inhibits Abeta generation by decreasing the expression of APP, PS1, and beta-secretase (BACE1) through the RhoA/ROCK/Erk signaling pathway but also reduces Abetao neurotoxicity by decreasing the expressions of apoptosis-related p53 target genes. In APP/PS1 mice, specific reduction of the ArhGAP11A level in neurons significantly reduces Abeta production and plaque deposition and ameliorates neuronal damage, neuroinflammation, and cognitive deficits. Moreover, Abetaos enhance ArhGAP11A expression in neurons by activating E2F1, which thus forms a deleterious cycle. Our results demonstrate that ArhGAP11A may be involved in AD pathogenesis and that decreasing ArhGAP11A expression may be a promising therapeutic strategy for AD treatment. |
