Chen et al. (2026). npj Parkinson s Disease. doi: 10.1038/s41531-026-01443-3
…an investigator blinded to the genotype. ARTICLE IN PRESS ARTICLE IN PRESS Antibodies and Reagents The antibodies and reagents used in the study include: Anti-Tyrosine Hydroxylase (rabbit, 1:5000 for IF, Pel-Freez, P40101-0), Anti-Tyrosine Hydroxylase (mouse, 1:500 for IF, Millipore, MAB5280), Anti-Kinesin 5B heavy chain (mouse, 1:500 for WB, Millipore, MAB1614), Anti- Dynein medium chain (mouse, 1:1000 for WB,…
Pel-Freez products cited: Rabbit Anti-Tyrosine Hydroxylase (P40101)
Abstract
Mutations in PTEN-induced putative kinase 1 (PINK1) cause early-onset, autosomal-recessive Parkinson's disease (PD). While previous studies have shown age-related declines in dopamine release and ATP levels in Pink1-/- mice, the mechanisms remain unclear. Using a novel TH-Mito-Dendra2 transgenic mouse model to label dopaminergic neuron mitochondria, we show that PINK1 loss leads to age-dependent defects in axonal mitochondrial trafficking in acute brain slices. These deficits are characterized by reduced anterograde transport and increased mitochondrial stalling. Pharmacological induction of reactive oxygen species (ROS) and calcium release impaired mitochondrial mobility. Consistent with this, Pink1 knockout mice exhibited elevated mitochondrial calcium, oxidation levels, and p38 MAPK hyperactivation. Treatment with a calcium channel blocker and p38 inhibitor SB202190 restored mitochondrial motility and increased anterograde transport. Together, our findings suggest that PINK1 loss disrupts mitochondrial trafficking by disturbing calcium and redox homeostasis via the p38 pathway, contributing to PD pathogenesis.