New trigger for Parkinson’s discovered, may improve treatment options
New trigger for Parkinson's discovered, may improve treatment options
Uncovering the Synaptic Dysfunction in Parkinson’s Disease: A Pathway for New Treatments
Parkinson’s disease is a relatively common neurodegenerative disorder, affecting more than 10 million people worldwide. It is characterized by symptoms such as tremors, movement problems, balance issues, and coordination difficulties. The prevailing belief among experts is that the disease is caused by the death of dopamine-containing nerve cells in the brain region responsible for motor control. However, a recent study has shed new light on the disease, suggesting that synaptic dysfunction may actually precede the deterioration of these nerve cells.
Traditionally, Parkinson’s has been associated with the loss of dopamine-containing neurons in the substantia nigra region of the brain. These low dopamine levels lead to the characteristic symptoms of the disease. However, researchers have now discovered that the malfunctioning of synapses, the connections between nerve cells, may be the initial event leading to Parkinson’s.
The study was prompted by the observation of two sisters who both developed early-onset Parkinson’s disease. Genetic analysis revealed that both sisters had a loss-of-function mutation in a gene called PTEN-induced kinase 1 (PINK1), which usually has a neuroprotective role. Additionally, the sister diagnosed at 16 had inherited a mutation in another gene, parkin, which is involved in removing or recycling worn-out mitochondria in the synapse.
Mutations in both of these genes impair the ability to recycle and eliminate defective mitochondria, leading to Parkinson’s disease. However, the researchers also discovered that parkin, but not PINK1, plays a role in controlling the release of dopamine in the synaptic terminal. Mutant parkin leads to defective recycling of vesicles, resulting in reduced dopamine release and the accumulation of toxic oxidized dopamine in neurons.
These findings suggest that synaptic dysfunction may occur before the death of dopaminergic neurons, challenging the long-held belief that the symptoms of Parkinson’s disease are solely a result of neuron deterioration. The authors of the study propose that targeting the synapses could be a potential strategy for early intervention and the prevention of neuronal damage.
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Currently, treatments for Parkinson’s disease focus on managing the symptoms and increasing dopamine levels in the brain. The most commonly prescribed drug is levodopa, which is converted into dopamine in the body. However, it can have unpleasant side effects. Another approach is the use of monoamine oxidase-b (MAO-B) inhibitors, which prevent the breakdown of dopamine. However, these treatments do not address the underlying synaptic dysfunction.
The new findings open up possibilities for developing therapies that target the parkin pathway, potentially slowing down or halting the progression of Parkinson’s disease before dopaminergic neurons are affected. The study’s lead author, Professor Dimitri Krainc, suggests that intervening early by targeting synaptic dysfunction could be key to treating Parkinson’s disease effectively.
Dr. Michael S. Okun, a national medical advisor at the Parkinson’s Foundation, commented on the study’s significance, stating that it uncovers a potential clue in the pathogenesis of Parkinson’s disease. Exploring this pathway and selectively activating parkin in the dopamine-containing synapse may lead to new therapeutic options for both genetic and sporadic forms of the disease.
In conclusion, the study highlights the importance of synaptic dysfunction in the development and progression of Parkinson’s disease. It challenges the conventional understanding of the disease as solely a result of neuron death. By targeting the synapses and addressing the malfunctioning parkin pathway, we may have a chance to intervene early and potentially develop more effective treatments for Parkinson’s disease.
