| ALDH2 protects against dopaminergic neuronal cell ferroptosis by enhancing the enzyme activity of PRDX6 in Parkinson's disease |
| 論文作者 |
Li, X; Peng, SJ; Wang, Y; Chen, X; Wu, TT; Feng, Y; Wang, XX; Yin, HY; Wu, YC |
| 期刊/會議名稱 |
NPJ PARKINSONS DISEASE |
| 論文年度 |
2025 |
| 論文類別 |
|
| 摘要 |
Emerging evidence suggests that ferroptosis is probably involved in the selective loss of dopaminergic neurons in Parkinson's disease (PD). Acetaldehyde dehydrogenase 2 (ALDH2) plays an important role in detoxifying lipid aldehydes derived from lipid peroxidation, a process that is closely linked to ferroptosis. In our study, ALDH2 knockout (KO) mice were more susceptible to the loss of tyrosine hydroxylase-positive neurons and behavioral changes in a PD mouse model. Similar observations were made in a knock-in (KI) mouse model with one of the most common single-nucleotide polymorphisms of ALDH2, rs671. Interestingly, ALDH2 KO or KI mice showed enhanced ferroptosis in the SN. Moreover, expression of ALDH2 modified the sensitivity of SH-SY5Y cells to ferroptosis inducers. Mechanistic studies have shown that ALDH2 regulates neuronal cell ferroptosis by interacting with the antioxidant enzyme peroxiredoxin 6 (PRDX6) to enhance its enzymatic activity, whereas the ALDH2 rs671 variant weakens its binding to PRDX6. |
| 卷 |
11 |
| 影響因子 |
8.2 |
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