Scientists have made a groundbreaking discovery about the origin of Parkinson’s disease, challenging a long-held belief. According to a study published in the journal Neuron, the malfunctioning of synapses, which are tiny gaps that allow neurons to communicate, may be a trigger for Parkinson’s disease.
Parkinson’s disease affects between 1% to 2% of the global population and is characterized by motor symptoms such as resting tremors, rigidity, and slowness of movement. These symptoms are caused by the loss of dopaminergic neurons in a specific area of the brain known as the substantia nigra pars compacta (SNc).
Traditionally, it was believed that the death of dopaminergic neurons was the initial event in Parkinson’s disease development. However, the new study suggests that dysfunction in synapses could precede their degeneration. This discovery could have significant implications for the development of novel therapeutic strategies.
The researchers became interested in this avenue of research after studying two sisters, both genetically predisposed to Parkinson’s disease. One sister was diagnosed at the age of 16, while the other was diagnosed at the age of 48. The sister diagnosed at 16 had a partial loss of the parkin gene, in addition to the PINK1 mutation, raising questions about parkin’s role in the disease.
PINK1 and parkin are involved in the process of recycling old or overworked mitochondria, known as mitophagy. Dysfunctional mitochondria can cause cellular dysfunction and potentially lead to Parkinson’s disease. The researchers used patient-derived midbrain neurons for their study, as findings in mouse models are not directly applicable to humans.
The study revealed that parkin has another role unrelated to mitophagy, involving the regulation of dopamine release within the synaptic terminal. This suggests that Parkinson’s disease starts with dysfunction in synapses, not the death of neurons. As a result, targeting dysfunctional synapses could represent a novel therapeutic strategy for Parkinson’s disease.
However, further studies are needed to develop effective strategies and therapeutics based on this discovery. Understanding the genetic basis of Parkinson’s in individual patients is important for developing personalized therapeutic strategies.
The study, titled “Parkinson’s disease-linked parkin mutation disrupts recycling of synaptic vesicles in human dopaminergic neurons,” was authored by Pingping Song, Wesley Peng, Veronique Sauve, Rayan Fakih, Zhong Xie, Daniel Ysselstein, Talia Krainc, Yvette C. Wong, Niccolò E. Mencacci, Jeffrey N. Savas, D. James Surmeier, Kalle Gehring, and Dimitri Krainc.
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