Powering Down in an Inherited form of Parkinson’s

New research establishes link between mitochondria dysfunction and dopamine in PINK1 model of disease

PHILADELPHIA -- Parkinson’s disease is a neurodegenerative disorder caused by the loss of neurons that produce dopamine. Hui Zhang’s research group at the Vickie & Jack Farber Institute for Neuroscience at Thomas Jefferson University is trying to understand how dopamine levels are affected by PINK1, a gene mutated in many cases of early-onset, inherited Parkinson’s.

PINK1 is a protein kinase that is located on mitochondria. It is thought protect against mitochondrial dysfunction, which has long been linked to Parkinson’s disease. But many questions remain as to whether and how PINK1 affects mitochondrial function and/or dopamine levels.

In this study, first author Lianteng Zhi and colleagues used a series of experiments to measure dopamine levels and mitochondrial function in brain slices collected from mice lacking the PINK1 gene. The findings were published in Neurobiology of Aging.

They found that PINK1 knock-out mice had less dopamine release, and that this decrease got worse with age. They also found that mitochondria were impaired in PINK1 knock-out animals, which was also age-dependent.

Based on these observations, the researchers suspected that the decrease in dopamine may be related to impaired mitochondrial function. Since impaired mitochondria produce less energy or ATP, to test their hypothesis, the researchers used chemicals to block ATP generation in normal mice to replicate mitochondrial impairment. As they guessed, these mice also showed a decrease in dopamine release.

Together, the findings provide more evidence to link mitochondrial dysfunction and dopamine in pre-clinical models for Parkinson’s disease. Further research could help identify novel therapeutic targets.

The study was funded by NINDS NS054773 and NS098393. The authors report no conflict of interest.

Article Reference: LiantengZhi,Qi Qin, Tanziyah Muqeem, Erin L.Seifert^,Wencheng Liu^,Sushuang Zheng, Chenjian Li, Hui Zhang, “Loss of PINK1 causes age-dependent decrease of dopamine release and mitochondrial dysfunction,” Neurobiology of Aging, DOI:10.1016/j.neurobiolaging.2018.10.025, 2018.

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