Management of Parkinson’s Disease through SNCA protein

Context

Researchers studying Parkinson’s disease are concentrating on lowering the levels of SNCA proteins in neurons as a potential treatment strategy.

What is Parkinson’s Disease?

Parkinson’s disease is a neurodegenerative condition that occurs in the elderly and is characterised by slow and relentless loss of neurons that use the neurotransmitter dopamine and other brain areas as a result of α-synuclein aggregation. It is a result of significant influences from genes and the environment.

What is SNCA Protein?

Alpha-synuclein protein also known as SNCA is a protein found in normal cells but its exact role has not been clarified. It is notorious for its implication in age-related neurodegenerative disorders. SNCA variants were initially linked with Parkinson’s disease 27 years ago. Parkinson’s disease is a disorder that affects people in that they lose some neurons which chemically communicate with each other in a particular region of the brain using dopamine as a neurotransmitter. It has been discovered that these neurons contain aggregated masses of proteins called Lewy bodies which have a dopaminergic nature. Typically most of these proteins are SNCA.

Two Forms of SNCA Protein

A recent study found two ways in which SNCA is present as aggregates in cells: one that hampers the normal functioning of cells’ nuclei and another that enables the protein to be degraded in case it has been misfolded. The researchers are able to determine that the former are linked to pathologic conditions and the latter is essential for healthy cells. Overall this study is valuable in emphasising the need to have proper balance between these two SNCA populations for regulating Parkinson’s disease.

Formation of Lewy Bodies

The researchers grew neurons on a neuronal plate outside a living organism and supplied them with nutrition in a dish. In these neurons they basically inserted some quantity of Lewy bodies seeds which are some amount of misfolded SNCA and thus created structures similar to Lewy bodies in the neurons. Over time, they found two SNCA populations in the cells: One was around the nuclei with a filamentous structure consisting of tens of micrometres in Lewy-like bodies. This other population was also present around the nuclei but in much smaller clumps and was identified as aggresomes. Thus such aggresomes are formed as when cells accumulate misfolded proteins into a small group (as collecting the trash into a corner) for further degradation.

Breaching the Nucleus

They found that those Lewy-body-like inclusions develop rather slowly. The aggresomes engulfed most of the SNCA proteins without permitting the structures to develop in a Lewy-body-like manner most of the time. However, in their experiment, when the researchers continuously inoculate the neurons with misfolded SNCA for their study, the Lewy-body-like structures begin to develop more rapidly, and when they have reached a certain size, they start to impact the other cellular mechanisms. They however became too numerous at one time for the aggresomes to be able to reduce their incidence. The Lewy-body-like structures were visibly enlarged and located at the nuclear periphery of cells; the researchers have opined that this could injure the nuclear envelope. On some occasions even the structures also went into the ruptured nuclei.

Therapeutic Target

There are no approved methods for treating Parkinson’ disease, however, there are some methods being developed by researchers which intend to prevent accumulation of SNCA in neurons. This can be done by reducing the quantity of SNCA in cells which would consequently imply reduced incidence of misfolded SNCA. One of these strategies is to stop the cells from expressing SNCA genes or degrade SNCA protein inside the cells. But such interventions have to be directed in particular to local areas to avoid the adverse effects on the entire body. Another potential approach is to avoid the ongoing formation of large SNCA aggregates by regulating SNCA amounts equally distributed between aggresomes and Lewy bodies. The further mechanism of how this balance is achieved is still being investigated.

Conclusion

In conclusion, balancing two forms of SNCA protein could help manage Parkinson’s disease. The study highlights the importance of striking a balance between these two SNCA populations to manage Parkinson’s disease. Researchers are focused on reducing the prevalence of SNCA in neurons as a therapeutic measure. However, the exact mechanism of how to achieve this balance is still being worked out. Further research is needed to understand the dynamics of the formation of these aggregates and how exactly they affect neurons.

Source: The hindu

UPSC Prelims Practice Question

Q.Which of the following statements about Parkinson’s Disease is/are correct?

1. Parkinson’s Disease is a neurodegenerative disorder that primarily affects movement.
2. It is caused by the loss of dopamine-producing neurons in the brain.
3. Symptoms of Parkinson’s Disease include tremors, rigidity, bradykinesia, and postural instability.
4. There is currently no cure for Parkinson’s Disease, but treatments can help manage symptoms.

Select the correct answer using the codes given below:

 a) 1 and 2 only
 b) 2 and 3 only
 c) 1, 2, and 3 only
 d) 1, 2, 3, and 4

Ans- d

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