ALDH2 protects against dopaminergic neuronal cell ferroptosis by enhancing the enzyme activity of PRDX6 in Parkinson's disease.

ABSTRACT: 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 studie

SUBMITTER: Li X 

PROVIDER: S-EPMC12689773 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature