Alpha-synuclein

Lewy bodies (alpha synuclein inclusions)

Lewy Body alphaSynuclein

Events in alpha synuclein toxicity

Alpha-synuclein is a protein that, in humans, is encoded by the SNCA gene. It is predominantly expressed in the brain, particularly in the neurons, and is involved in various neurological processes. Notably, alpha-synuclein plays a significant role in the regulation of dopamine release and transport. It is best known for its association with Parkinson's disease and other related neurodegenerative disorders, such as multiple system atrophy and dementia with Lewy bodies.

Structure and Function

Alpha-synuclein is a small, 140-amino acid protein that is natively unfolded; that is, it does not have a fixed or rigid three-dimensional structure. This lack of structure allows it to interact with a variety of biological molecules, playing roles in several cellular processes. Among its functions, alpha-synuclein is involved in synaptic vesicle regulation and neurotransmitter release, contributing to the normal operation of neuronal communication.

Pathology

The aggregation of alpha-synuclein into fibrils forming insoluble Lewy bodies is a hallmark of several neurodegenerative diseases, collectively known as synucleinopathies. In Parkinson's disease, the accumulation of Lewy bodies in the substantia nigra, a region of the brain involved in movement control, leads to the degeneration of neurons and the characteristic symptoms of the disease, such as bradykinesia, rigidity, and tremor.

Mutations in the SNCA gene, such as the A53T and E46K mutations, have been linked to familial forms of Parkinson's disease, suggesting a genetic component to the disorder. Additionally, duplication or triplication of the SNCA gene can increase the expression of alpha-synuclein, leading to an early onset of the disease.

Research and Therapeutic Approaches

Research into alpha-synuclein has focused on understanding its role in neurodegeneration and developing therapeutic strategies to prevent its aggregation. Approaches include small molecules that inhibit aggregation, immunotherapy targeting alpha-synuclein aggregates, and gene therapy aimed at reducing SNCA gene expression. These strategies are in various stages of research and clinical trials, offering hope for new treatments for Parkinson's disease and other synucleinopathies.

See Also

• Parkinson's disease
• Neurodegeneration
• Lewy body
• Synucleinopathy
• Neurotransmitter

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