What is alpha synuclein aggregation?
The aggregation of α-synuclein (α-syn) is inseparably connected to Parkinson’s disease (PD). It is now well-established that certain forms of α-syn aggregates, oligomers and fibrils, can exert neurotoxicity in synucleinopathies. With the exception of rare familial forms, the vast majority of PD cases are idiopathic.
Where do Lewy bodies aggregate?
These are insoluble protein aggregates forming fibrils and composed mainly but not exclusively of α-synuclein (Fig. 1a, b) [6, 141]. In Parkinson’s disease, Lewy bodies are mainly found at predilection sites of neuronal loss, i.e. the substantia nigra and locus coeruleus.
How does alpha synuclein cause Parkinson’s?
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 is phosphorylated alpha synuclein?
Phosphorylated α-synuclein (PS-129), a protein implicated in the pathogenesis of Parkinson’s disease (PD), was identified by mass spectrometry in human cerebrospinal fluid (CSF).
What is alpha-synuclein and 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 causes alpha-synuclein aggregation?
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 causes alpha synuclein aggregation?
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 a Synucleinopathy?
Synucleinopathies are a group of neurodegenerative disorders in which the protein alpha-synuclein accumulates abnormally to form inclusions in the cell bodies or axons of neurons or oligodendrocytes.