Possible Advancement In Our Understanding Of Parkinson’s Disease Is Made Possible By The Genetic Riddle Involving Two Sisters

Possible Advancement In Our Understanding Of Parkinson's Disease Is Made Possible By The Genetic Riddle Involving Two Sisters | The Lifesciences Magazine

Researchers have disproved a long-held theory about the causes of Parkinson’s disease in a ground-breaking study that was published in the journal Neuron, putting new light on this crippling neurological disorder. Their findings suggest that one possible cause of Parkinson’s disease may be the dysfunction of synapses, the microscopic openings at which neurons can connect with one another. This information gives up exciting new opportunities for prospective treatments that may have a big positive effect on the lives of those who are afflicted by the condition.

A neurological ailment called Parkinson’s disease, which affects 1% to 2% of the world’s population, is common. It is characterised by a variety of motor symptoms, such as slowness of movement, rigidity, and resting tremors. These symptoms are caused by the progressive death of dopaminergic neurons in the substantia nigra pars compacta (SNc), a particular region of the brain.

Research into Parkinson’s illness has long been a challenging puzzle. Though the exact cause is yet unknown, ageing, environmental variables, and hereditary factors all seem to be involved. Dopaminergic neurons, which create the essential neurotransmitter dopamine, are understood to be key players in the illness.

It was once widely believed that the first sign of Parkinson’s disease was the death of dopaminergic neurons. This recent study disputes that notion, contending that the malfunction in the synapses of these neurons might occur before their degeneration.

A unusual example involving two sisters who were both genetically predisposed to Parkinson’s disease as a result of a mutation in the PINK1 gene is what initially spurred interest in this particular line of investigation. One sister was diagnosed when she was 16 years old, while the other was diagnosed when she was 48 years old.

The study’s principal investigator, Dimitri Krainc, MD, chair of neurology at Northwestern University Feinberg School of Medicine and director of the Simpson Querrey Centre for Neurogenetics, said, “We encountered two sisters with Parkinson’s disease whose disease onset was 30 years apart, and we tried to explain this discrepancy by studying their genes.”

They found that in addition to having the PINK1 mutation, the sibling who was identified at age 16 also had a partially lost parkin gene. The scientists started to wonder if parkin played a hitherto unrecognised role in the illness after this discovery.

“To cause Parkinson’s disease, parkin must completely disappear. What accounts for the sister’s more than 30-year delay in developing the condition while having only a partial deletion of parkin? stated Krainc.

Parkin and PINK1 are both involved in the “recycling” of ageing or overworked mitochondria. If untreated, dysfunctional mitochondria can lead to cellular dysfunction. Mitophagy is the name given to the process of recycling damaged mitochondria. Parkinson’s disease can develop in people who have mutations in either the parkin or PINK1 gene in both copies due to inefficient mitophagy.

Due to the physiological differences between mouse and human dopamine neurons, which prevent results from animal models from being directly transferred to humans, the researchers had to conduct their investigation using patient-derived midbrain neurons.

The researchers found that parkin plays an additional important but previously unidentified role. Parkin functions in a separate pathway within the synaptic terminal in addition to its recycling role. This route controls the release of dopamine and is unrelated to mitophagy.

The most important thing to remember is that Parkinson’s disease does not always start with neuronal death. Instead, it begins with the breakdown of synapses, which serve as the centres for the exchange of critical information between neurons. The results suggest, in Krainc’s words, “that Parkinson’s starts with dysfunction of the synapse much before neurons start degenerating.”

This finding is significant because it suggests a unique therapy approach for Parkinson’s disease may involve targeting defective synapses. We may have a higher chance of successfully managing or perhaps preventing the crippling consequences of Parkinson’s by acting before neuron loss takes place.

Krainc emphasised that there are limitations and unanswered concerns despite the research’s renewed optimism. He said, “We need to find a way to therapeutically target such synaptic dysfunction as early as possible.” In other words, the path to a useful medicine based on this discovery is still under construction, and more research is required to identify efficient approaches.

However, this study’s ramifications are significant. It emphasises how crucial it is to comprehend how Parkinson’s disease develops genetically in each patient. According to Krainc, “It is important to examine the genes of each Parkinson’s patient because knowing the genetic basis of the disease helps with therapeutic strategies.”

Researchers Pingping Song, Wesley Peng, Veronique Sauve, Rayan Fakih, Zhong Xie, Daniel Ysselstein, Talia Krainc, Yvette C. Wong, Niccol E. Mencacci, Jeffrey N. Savas, D. James Surmeier, Kalle Gehring, and Dimitri Krainc published their findings in the journal Neuron.

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