| Autor: |
Basurto-Islas, Gustavo, Tung, Yunn Chyn, Dai, Chun-ling, Iqbal, Khalid, Gong, Cheng-Xin |
| Zdroj: |
Journal of Alzheimer's Disease Reports; January 2024, Vol. 8 Issue: 1 p615-626, 12p |
| Abstrakt: |
Background: Diabetes mellitus (DM) increases the risk for cognitive impairment and Alzheimer’s disease (AD). Diabetic ketoacidosis (DKA), a serious complication of DM, may also cause brain damage and further AD, but the underlying molecular mechanisms remain unclear.Objective: Our objective was to understand how DKA can promote neurodegeneration in AD.Methods: We induced DKA in rats through intraperitoneal injection of streptozotocin, followed by starvation for 48 hours and investigated AD-related brain alterations focusing on tau phosphorylation.Results: We found that DKA induced hyperphosphorylation of tau protein at multiple sites associated with AD. Studies of tau kinases and phosphatases suggest that the DKA-induced hyperphosphorylation of tau was mainly mediated through activation of c-Jun N-terminal kinase and downregulation of protein phosphatase 2A. Disruption of the mTOR-AKT (the mechanistic target of rapamycin−protein kinase B) signaling pathway and increased levels of synaptic proteins were also observed in the brains of rats with DKA.Conclusions: These results shed some light on the mechanisms by which DKA may increase the risk for AD. |
| Databáze: |
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