{Reference Type}: Journal Article
{Title}: BL-918 activates PINK1/Parkin signaling pathway to ameliorate the progression of Parkinson's disease.
{Author}: Wang Y;Luo S;Su H;Wang Z;Chu L;Zhang C;
{Journal}: J Biol Chem
{Volume}: 300
{Issue}: 8
{Year}: 2024 Jul 9
暂无{DOI}: 10.1016/j.jbc.2024.107543
{Abstract}: The pathogenesis of Parkinson's disease (PD) has been associated with mitochondrial dysfunction. Given that the PINK1/Parkin pathway governs mitochondrial quality control by inducing mitophagy to remove damaged mitochondria, therapeutic approaches to activate PINK1/Parkin-mediated mitophagy have the potential in the treatment of PD. Here, we have identified a new small molecule, BL-918, as an inducer of mitophagy via activating the PINK1/Parkin pathway. BL-918 triggers PINK1 accumulation and Parkin mitochondrial translocation to initiate PINK1/Parkin-mediated mitophagy. We found that mitochondrial membrane potential and mitochondrial permeability transition pore were involved in BL-918-induced PINK1/Parkin pathway activation. Moreover, we showed that BL-918 mitigated PD progression in MPTP-induced PD mice in a PINK1-dependent manner. Our results unravel a new activator of the PINK1/Parkin signaling pathway and provide a potential strategy for the treatment of PD and other diseases with dysfunctional mitochondria.