What is alpha-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 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 alpha-synuclein structure?

α-Syn is a small acidic protein with three domains namely N-terminal lipid-binding α-helix, amyloid-binding central domain (NAC), and C-terminal acidic tail.

What type of mutation is alpha-synuclein?

α-Synuclein was the first of the genes found to be mutated in a familial form of PD. Point mutations are located at three amino acids, A53T, A30P, and E46K, and act as gain-of-function mutations, consistent with the autosomal dominant pattern of inheritance.

What kind of protein is alpha-synuclein?

Alpha-synuclein is a synuclein protein of unknown function primarily found in neural tissue, making up as much as 1% of all proteins in the cytosol of brain cells. It is predominantly expressed in the neocortex, hippocampus, substantia nigra, thalamus, and cerebellum.

Where does alpha-synuclein aggregation?

These abnormal protein deposits are mostly composed of aggregated α-synuclein (α-Syn). In the particular case of PD, α-Syn aggregation occurs in the dopaminergic neurons of substantia nigra pars compacta.

What does alpha-synuclein protein do?

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.

How does alpha-synuclein misfolded?

Functional misfolding of α-synuclein. The partial compactness of α-synuclein represents an illustration of a functional misfolding concept, according to which intrinsically disordered proteins (IDPs) contain the preformed binding elements which might be involved in a set of non-native intramolecular interactions.

What type of protein is alpha-synuclein?

What is the role of α synuclein in the pathology of the disease?

α-Synuclein may contribute to PD pathogenesis in a number of ways, but it is generally thought that its aberrant soluble oligomeric conformations, termed protofibrils, are the toxic species that mediate disruption of cellular homeostasis and neuronal death, through effects on various intracellular targets, including …

What are Lewy bodies and alpha-synuclein?

Alpha-synuclein plays a key role in both Parkinson’s disease and DLB. This protein is the major component of Lewy bodies — protein clumps that develop inside nerve cells and contribute to neurodegeneration.

Is synuclein alpha a protein?

Alpha-synuclein 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. It is abundant in the brain, while smaller amounts are found in the heart, muscle and other tissues.

What is the structure of the alpha synuclein?

ALPHA-SYNUCLEIN STRUCTURE. α-Syn is a small acidic protein with three domains namely N-terminal lipid-binding α-helix, amyloid-binding central domain (NAC), and C-terminal acidic tail. The N-terminal domain of α-syn (residues 1–87) is a positively charged region, including seven series of 11-AA repeats.

How are α-synuclein misfolding and aggregation related to PD?

Lewy bodies and Lewy neurites are the pathological hallmarks of PD and contain α-Syn aggregates as their major component. It was therefore hypothesized that α-Syn aggregation is actively associated with PD pathogenesis.

What is the role of alpha synuclein oligomerization?

Citation: Wan OW, Chung KKK (2012) The Role of Alpha-Synuclein Oligomerization and Aggregation in Cellular and Animal Models of Parkinson’s Disease. PLoS ONE 7 (6): e38545. https://doi.org/10.1371/journal.pone.0038545 Editor: Philipp J. Kahle, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, Germany

How is aggregation related to the phenotype of PD?

However, the correlation between aggregation propensities of α-Syn mutants and their association with PD phenotype is not straightforward. Recent evidence suggested that oligomers, formed during the initial stages of aggregation, are the potent neurotoxic species causing cell death in PD.