α-Synuclein has been shown to regulate the production of dopamine in cultured cells through its interaction with tyrosine hydroxylase (TH), the rate-limiting enzyme responsible for converting tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA) in the dopamine synthesis pathway [35,36] (Figure 2).
What is alpha-synuclein and what is known about its role in Parkinson's disease?
Alpha-synuclein (α-Syn) is a key protein involved in Parkinson's disease (PD) pathology. PD is characterized by the loss of dopaminergic neuronal cells in the substantia nigra pars compacta and the abnormal accumulation and aggregation of α-Syn in the form of Lewy bodies and Lewy neurites.
What is alpha-synuclein in the brain?
Alpha-synuclein is a small synaptic protein that was identified as a major component of Lewy bodies and Lewy neurites in the brain of patients affected by Parkinson's disease (PD), Lewy body dementia (LBD), and other synucleinopathies.
What disease does synuclein cause?
Alpha-synuclein (αS) is the major constituent of Lewy bodies and a pathogenic hallmark of all synucleinopathathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).
Where are Lewy bodies found in Parkinson's?
SUMMARY The Lewy body is a distinctive neuronal inclusion that is always found in the substantia nigra and other specific brain regions in Parkinson's disease. It is mainly composed of structurally altered neurofilament, and occurs wherever there is excessive loss of neurons.
What part of the brain is affected by Parkinson's disease?
Parkinson's disease (PD) is a neurodegenerative disorder that affects predominately dopamine-producing (“dopaminergic”) neurons in a specific area of the brain called substantia nigra.
What chromosome is the SNCA gene located?
The SNCA gene is located on the long arm of chromosome 4 (4q21. 3-22).
What does alpha-synuclein normally do?
α-Synuclein localizes specifically to the nerve terminal and inhibits neurotransmitter release when over-expressed, but the knockout has a modest effect on synaptic transmission, suggesting alternative presynaptic roles.
What is aggregated alpha-synuclein?
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 misfolded alpha-synuclein?
The reason why alpha-synuclein becomes misfolded in the brain or the gut is unknown. We hypothesize that alpha-synuclein misfolding in gut and brain neurons in caused by exposure to proteins of similar structure that are contained in bacteria that reside in the mouth and gut.
How does alpha-synuclein cause Parkinsons?
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
How does alpha-synuclein spread?
Small lipid vesicles called exosomes may play a role in the spread and toxicity of α-synuclein. Exosomes are released by neurons and other cell types and can be formed either by direct budding from the plasma membrane, or are released internal vesicles of multivesicular bodies.Mar 6, 2020
What kind of protein is alpha-synuclein?
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.
Is alpha-synuclein a monomer?
Alpha-synuclein may exist predominantly as either a monomer or a variety of oligomers of different molecular weights.
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).Mar 4, 2021