Balancing two forms of SNCA protein could help manage Parkinson’s, study finds
- May 20, 2024
- Posted by: OptimizeIAS Team
- Category: DPN Topics
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Balancing two forms of SNCA protein could help manage Parkinson’s, study finds
Sub: Science and tech
Sec: Health
Context:
- Many Parkinson’s disease researchers are focused on reducing the prevalence of SNCA proteins in neurons as a therapeutic measure.
What is Parkinson’s disease?
- Parkinson’s disease is a chronic, degenerative neurological disorder that affects the central nervous system.
- It damages nerve cells in the brain, dropping the levels of dopamine.
- Dopamine is a chemical that sends behavioral signals from the brain to the body.
- The disease causes a variety of “motor” symptoms (symptoms related to movement of the muscles), including rigidity, delayed movement, poor balance, and tremors.
- Medication can help control the symptoms of the disease but it can’t be cured.
- It affects the age group from 6 to 60 years. Worldwide, about 10 million people have been affected by this disease.
- Parkinson’s is treated symptomatically by increasing the levels of dopamine or, more drastically, by grafting new neurons in place of dead ones.
- An SNCA-based solution is more desirable because it offers a more sustainable resolution.
What are SCNA proteins?
- Synuclein alpha (SNCA) is a mysterious protein.
- Alpha-synuclein (aSyn) is a protein that, in humans, is encoded by the SNCA gene.
- Alpha-synuclein is a neuronal protein that regulates synaptic vesicle trafficking and subsequent neurotransmitter release.
- SNCA is abundant in neurons, especially in dopaminergic neurons.
- It is found near the nuclei of these cells and at the junctions between two neurons.
- It is capable of misfolding as well as forming filamentous structures.
- So unlike most other proteins, which take up predictable three-dimensional structures, SNCA can fold in multiple ways.
- Misfolded proteins don’t function correctly.
- It promotes Neuronal Dysfunction and Death by Disrupting the Binding of Ankyrin to beta-Spectrin.
- Twenty-seven years ago, researchers first associated SNCA with Parkinson’s disease.
- Diseases associated with SNCA include Parkinson Disease 1, Autosomal Dominant and Dementia, Lewy Body.
About the study:
- SNCA is present as aggregates in cells in two ways:
- one that interferes with the structural integrity of cells’ nuclei and
- another that allows the cell to degrade misfolded proteins.
- The researchers found that the former are related to diseased states while the latter is important for healthy cells.
- The study highlights the importance of striking a balance between these two SNCA populations to manage Parkinson’s disease.
- Cultivation of neurons: The researchers cultivated neurons outside a living body, providing them with nutrients in a laboratory setup.
- Artificially created structure: In these neurons, they artificially created structures resembling Lewy bodies by adding some amount of misfolded SNCA, called seeds.
- Two SCNA populations: Over time, two SNCA populations in the cells are witnessed.
- One was around the nuclei, shaped like filaments tens of micrometers long, much like Lewy bodies.
- The other population was also around the nuclei but as much smaller clumps called aggresomes.
- Such aggresomes are formed when cells localize misfolded proteins into a small bunch (like collecting the trash in a corner) for further processing.
- When the researchers repeatedly seeded neurons with misfolded SNCA, the Lewy-body-like structures formed faster and became big enough to affect other parts of the cell.
About nucleus of the cell:
- A nucleus is the control center of the cell.
- It contains the cell’s genetic material, and is the seat of upkeep of this genetic material and its utilization to make proteins.
- The accumulation of misfolded SNCA would render the nucleus dysfunctional and eventually kill it.
- Lewy-body-like structures can pass from one cell to another, so the effect could cascade to neighboring cells as well.
Various therapeutic impacts:
- A smaller population of SNCA means fewer misfolded SNCA.
- This can be achieved by stopping the SNCA gene from expressing itself or by destroying the SNCA protein inside cells, once the cells make them.
- Another workable solution has been to use a gene-silencing tool, like CRISPR-Cas9, at a precise location.
Terms in news:
Lewy Bodies:
- Lewy bodies are clumps of abnormal protein particles that, for reasons that are not fully understood, accumulate in the brain.
- These deposits cause a form of dementia called Lewy body dementia, or LBD — which is what the late actor and comedian Robin Williams suffered from.
CRISPR:
- CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats.
- CRISPR-Cas9 is the most prominent technology that enables editing parts of the genome by removing, adding or altering sections of the DNA sequence.
- The CRISPR-Cas9 system consists of two key molecules that introduce a change mutation into the DNA.
- Cas9- An enzyme that acts as a pair of ‘molecular scissors’ that can cut the two strands of DNA at a specific location in the genome.
- Guide RNA (gRNA)- The gRNA is designed to find and bind to a specific sequence in the DNA.