Gene expression impacts brain aging  on July 20, 2024


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✅ Loss of PINK1 causes age-dependent mitochondrial trafficking deficits in nigrostriatal dopaminergic neurons through aberrant activation of p38 MAPK

science

Mutations in PTEN-induced putative kinase 1 (PINK1) gene cause early-onset, autosomal-recessive familial inherited Parkinson disease (PD). Previous studies have shown age-related declines in dopamine release and ATP levels in the striatum of Pink1-/- mice, but the underlying mechanisms remain unclear. While, the role of PINK1 in mitochondrial transport has been studied in cell culture and Drosophila, its impacts on axonal transport in dopaminergic neurons and the consequent synaptic and axonal degeneration in vivo remain critical questions that warrant further investigation. In this study, we developed a TH-mito-Dendra2 transgenic mouse model to label mitochondria in dopaminergic neurons with Dendra2 protein. Using this model, we found that loss of PINK1 causes age-dependent deficits in mitochondrial axonal trafficking, with reduced ...

BioRxiv     Jul 20, 2024