What is the function of alpha-synuclein?
What is the function of alpha-synuclein?
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 cause neurodegeneration?
Excess intracellular calcium enhanced cytosolic dopamine, and AS was required for death induced by excess dopamine, creating a possible scenario in which intracellular calcium, cystolic dopamine, and α-synuclein interact with each other in a self-feeding cascade leading to neurodegeneration (Mosharov et al. 2009).
Is alpha-synuclein a membrane protein?
With only 140 amino acids, α-Synuclein (α-Syn) is a small peripheral membrane protein that localizes specifically to the axon terminal in neurons (Maroteaux et al., 1988; George et al., 1995; Iwai et al., 1995; Bendor et al., 2013).
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 are alpha-synuclein aggregates?
α-Synuclein is an aggregation-prone neural protein that plays a central role in the pathogenesis of both sporadic and familial Parkinson’s disease (PD). Elevated level of wild-type α-synuclein is disease causative and demonstrates the essential need for precise regulation of α-synuclein expression.
What is α synuclein aggregation?
Is alpha-synuclein a prion?
Using the modern definition, α-synuclein aggregates should unequivocally be classified as prions, as there is strong evidence that α-synuclein can polymerize into aggregates that are able to self-multiply during disease, leading to “cellular transmission” of protein aggregation [8].
How does alpha-synuclein spread?
Alpha-synuclein inclusions, the hallmarks of synucleinopathies, are suggested to spread along neuronal connections in a stereotypical pattern in the brains of patients. Ample evidence now supports that pathological forms of alpha-synuclein propagate in cell culture models and in vivo in a prion-like manner.
What causes the formation of alpha synuclein oligomers?
The primary event underlying the formation of alpha-synuclein oligomers is thought to be the initiation of abnormal alpha-synuclein self-interaction, beginning with alpha-synuclein dimers, whose formation has been shown to be the rate-limiting step for alpha-synuclein aggregation ( Krishnan et al., 2003; Roostaee et al., 2013 ).
How is alpha synuclein related to Parkinson’s disease?
As the self-interaction of alpha-synuclein is thought to be intimately involved in the initiation of pathogenic processes of Parkinson’s disease ( Caughey and Lansbury, 2003 ), we hypothesized that a method to detect self-interacting alpha-synuclein molecules in human tissue could reveal earlier pathology.
Where is alpha synuclein more abundant in the brain?
Diffuse alpha-synuclein proximity ligation assay signal is significantly more abundant in patients compared to controls in regions including the cingulate cortex (1.6-fold increase) and the reticular formation of the medulla (6.5-fold increase).
How does aggregation of α-Syn play a role in PD?
It has been proposed that aggregation of α-syn contributes to the formation of LBs, which then leads to neurodegeneration in PD. However, studies have also suggested that aggregates formation is a protective mechanism against more toxic α-syn oligomers.
