NEW YORK: Degeneration of dopaminergic neurons is widely accepted as the first event that leads to Parkinson’s. However, a new study has challenged this common belief.
The study by a group of US researchers, published in the journal Neuron, suggests that a dysfunction in the neuron’s synapses -- the tiny gap across which a neuron can send an impulse to another neuron -- leads to deficits in dopamine and precedes neurodegeneration.
Parkinson’s disease affects 1-2 per cent of the population and is characterised by resting tremor, rigidity and bradykinesia (slowness of movement).
These motor symptoms are due to the progressive loss of dopaminergic neurons in the midbrain.
The findings open a new avenue for therapies, the scientists said.
“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.
Based on these findings, “we hypothesise that targeting dysfunctional synapses before the neurons are degenerated may represent a better therapeutic strategy,” Krainc added.
There are two genes -- Parkin and PINK1. It has been well-established that people who carry mutations in both copies of either PINK1 or Parkin develop Parkinson’s disease.
The study looked at two sisters who had the misfortune of being born without the PINK1 gene, because their parents were each missing a copy of the critical gene.
One sister was diagnosed at age 16 while the other was not diagnosed until she was 48.
The reason for the disparity led to an important new discovery by Krainc and his group. The sister who was diagnosed at 16 also had partial loss of Parkin, which, by itself, should not cause Parkinson’s.
“There must be a complete loss of Parkin to cause Parkinson’s disease. So, why did the sister with only a partial loss of Parkin get the disease more than 30 years earlier?” Krainc asked.
As a result, the scientists realised that Parkin has another important job that had previously been unknown.
Northwestern scientists saw a new opportunity to boost Parkin and the potential to prevent the degeneration of dopamine neurons.
“Now, we need to develop drugs that stimulate this pathway, correct synaptic dysfunction and hopefully prevent neuronal degeneration in Parkinson’s,” said Krainc.