DCBLD1 Inhibits the Progression of Parkinson's Disease by Regulating Apoptosis and Autophagy.

Parkinson's disease (PD) is a progressive neurodegenerative disease. This study aims to investigate the role of discoidin, CUB and LCCL domain containing 1 (DCBLD1) in PD. GSE156926 is used to analyze the differentially expressed genes in PD patients. 1-Methyl-4-phenylpyridinium (MPP+) is used to establish in vitro PD models. mRNA expression is detected using quantitative reverse transcriptase PCR (qRT-PCR). Protein expression is determined using Western blot. LC3 puncta expression is detected using immunofluorescence assay. Cell viability is detected using Cell Counting Kit-8 (CCK-8) assay. Neuronal apoptosis is determined using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. We found that DCBLD1 is downregulated in PD, which induces neuronal apoptosis and autophagy inhibition. Interestingly, overexpressed DCBLD1 inhibits neuronal apoptosis as well as restores autophagy and neuronal function. Moreover, DCBLD1 mediates the upregulation of transcription factor EB (TFEB). However, TFEB knockdown-induced autophagy inhibition alleviates the effects of DCBLD1 and contributes to neuronal apoptosis. In summary, DCBLD1 protects against neuronal apoptosis in PD via activating TFEB. Therefore, targeting DCBLD1/TFEB axis may be a promising strategy for PD.