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Alpha-synuclein is a synuclein protein primarily found in neural tissue, making up as much as one percent of all proteins in the cytosol of brain cells. [17] It is expressed highly in neurons within the frontal cortex, hippocampus, striatum, and olfactory bulb, [17] but can also be found in the non-neuronal glial cells. [18]
The DNA repair function of alpha-synuclein appears to be compromised in Lewy body inclusion bearing neurons, and this may trigger cell death. Study of synucleinopathy mouse models of Parkinson's disease indicates that alpha-synuclein pathogenesis is associated with increased DNA damage and activation of the DNA damage response. [19]
Mutations in alpha-synuclein are associated with early-onset familial Parkinson's disease and the protein aggregates abnormally in Parkinson's disease, Lewy body disease, and other neurodegenerative diseases. [5] [6] The gamma-synuclein protein's expression in breast tumors is a marker for tumor progression. [7] [8]
Alpha-synuclein is an intracellular protein typically localized to presynaptic terminals and involved in synaptic vesicle trafficking, intracellular transport, and neurotransmitter release. [ 102 ] [ 104 ] When misfolded , it can aggregate into oligomers and proto-fibrils that in turn lead to Lewy body formation.
Alpha-synuclein modulates DNA repair processes, including repair of DNA double-strand breaks (DSBs) by the process of non-homologous end joining [13] The repair function of alpha-synuclein appears to be greatly reduced in Lewy body bearing neurons, and this reduction may trigger cell death.
The conformation of the alpha-synuclein is different from that of alpha-synuclein in Lewy bodies. [3] The disease probably starts with an oligodendrogliopathy. [ 34 ] It has been proposed that the α-synuclein inclusions found in Oligodendrocytes result from the pruning and the engulfment of diseased axonal segments containing aggregated α ...
Positive Alpha-Synuclein staining of a Lewy body in a patient with Parkinson's disease. Braak staging refers to two methods used to classify the degree of pathology in Parkinson's disease and Alzheimer's disease. These methods are used both in research and for the clinical diagnosis of these diseases and are obtained by performing an autopsy of ...
An anti-α-synuclein drug, or an α-synuclein inhibitor, is a drug which blocks or inhibits α-synuclein. [1] [2] α-Synuclein is a protein which is thought to be involved in the development and progression of α-synucleinopathies including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy.