| First Author | Hashim KNB | Year | 2024 |
| Journal | FEBS Lett | Volume | 598 |
| Issue | 13 | Pages | 1576-1590 |
| PubMed ID | 38789405 | Mgi Jnum | J:350542 |
| Mgi Id | MGI:7663050 | Doi | 10.1002/1873-3468.14895 |
| Citation | Hashim KNB, et al. (2024) Neuronal glutathione depletion elevates the Abeta42/Abeta40 ratio and tau aggregation in Alzheimer's disease mice. FEBS Lett 598(13):1576-1590 |
| abstractText | Alzheimer's disease (AD) involves reduced glutathione levels, causing oxidative stress and contributing to neuronal cell death. Our prior research identified diminished glutamate-cysteine ligase catalytic subunit (GCLC) as linked to cell death. However, the effect of GCLC on AD features such as amyloid and tau pathology remained unclear. To address this, we investigated amyloid pathology and tau pathology in mice by combining neuron-specific conditional GCLC knockout mice with amyloid precursor protein (App) knockin (KI) or microtubule-associated protein tau (MAPT) KI mice. Intriguingly, GCLC knockout resulted in an increased Abeta42/40 ratio. Additionally, GCLC deficiency in MAPT KI mice accelerated the oligomerization of tau through intermolecular disulfide bonds. These findings suggest that the decline in glutathione levels, due to aging or AD pathology, may contribute to the progression of AD. |
