What causes aggregation of alpha-synuclein?

Impairments in mitochondrial function or an increase in oxidative stress can induce protein modifications that facilitate the conversion of α-synuclein to a fibrillar pathway. Changes in membrane composition or changes in expression of binding partners can initiate α-synuclein aggregation.

What is α-Synuclein aggregation?

α-Synuclein is a protein that aggregates as amyloid fibrils in the brains of patients with Parkinson’s disease and dementia with Lewy bodies. Small oligomers of α-synuclein are neurotoxic and are thought to be closely associated with disease.

What is the role of the α-Synuclein protein?

Alpha-synuclein is a neuronal protein that regulates synaptic vesicle trafficking and subsequent neurotransmitter release. It is abundant in the brain, while smaller amounts are found in the heart, muscle and other tissues.

Where does alpha-synuclein aggregation?

Protein Aggregation Disorders α-Synuclein is widely expressed in the brain, in both neuronal and nonneuronal cell types, including dopaminergic neurons, cortical neurons, noradrenergic neurons, endothelial cells, and platelets [62–64].

Is there a small molecule that inhibits α synuclein aggregation?

In PD, the typical pathological hallmark is the accumulation of intracellular protein inclusions, known as Lewy bodies and Lewy neurites, which are mainly composed of α-synuclein. Here, we exploited a high-throughput screening methodology to identify a small molecule (SynuClean-D) able to inhibit α-synuclein aggregation.

How is α-synuclein involved in Parkinson’s disease?

Parkinson’s disease is characterized by the presence in brain tissues of aberrant aggregates primarily formed by the protein α-synuclein. It has been difficult, however, to identify compounds capable of preventing the formation of such deposits because of the complexity of the aggregation process of α-synuclein.

Why is Beta synuclein important to the central nervous system?

Beta-synuclein. Beta-synuclein is suggested to be an inhibitor of alpha-synuclein aggregation, which occurs in neurodegenerative diseases such as Parkinson’s disease. Thus, beta-synuclein may protect the central nervous system from the neurotoxic effects of alpha-synuclein and provide a novel treatment of neurodegenerative disorders.

Is the SNCB gene homologous to alpha synuclein?

Beta-synuclein is a protein that in humans is encoded by the SNCB gene. The protein encoded by this gene is highly homologous to alpha-synuclein. These proteins are abundantly expressed in the brain and putatively inhibit phospholipase D2 selectively.

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