A new study challenges a common belief in what triggers Parkinson's disease. Degeneration of dopaminergic neurons is widely accepted as the first event that leads to Parkinson's. But the new study suggests that a dysfunction in the neuron's synapses leads to deficits in dopamine and precedes the neurodegeneration. The findings open a new avenue for therapies in which drugs target neuron synapses before neurons degenerate.
A new Northwestern Medicine study challenges a common belief in what triggers Parkinson's disease.
"We showed that dopaminergic synapses become dysfunctional before neuronal death occurs," said lead author Dr. Dimitri Krainc, chair of neurology at Northwestern University Feinberg School of Medicine and director of the Simpson Querrey Center for Neurogenetics."Based on these findings, we hypothesize that targeting dysfunctional synapses before the neurons are degenerated may represent a better therapeutic strategy.
It has been well-established that people who carry mutations in both copies of either PINK1 or Parkin develop Parkinson's disease because of ineffective mitophagy.Two sisters had the misfortune of being born without the PINK1 gene, because their parents were each missing a copy of the critical gene. This put the sisters at high risk for Parkinson's disease, but one sister was diagnosed at age 16, while the other was not diagnosed until she was 48.
"We discovered a new mechanism to activate Parkin in patient neurons," Krainc said."Now, we need to develop drugs that stimulate this pathway, correct synaptic dysfunction and hopefully prevent neuronal degeneration in Parkinson's."
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