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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 .
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]
Alpha synuclein, having no single, well-defined tertiary structure, is an intrinsically disordered protein, [77] [78] with a pI value of 4.7, [79] which, under certain pathological conditions, can misfold in a way that exposes its core hydrophobic residues to the intracellular milieu, thus providing the opportunity for hydrophobic interactions ...
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]
A Lewy body is composed of the protein α-synuclein associated with other proteins, such as ubiquitin, [9] neurofilament protein, and alpha B crystallin. Tau proteins may also be present, and Lewy bodies may occasionally be surrounded by neurofibrillary tangles .
This gene encodes a protein containing several protein-protein interaction domains, including ankyrin-like repeats, a coiled-coil domain, and an ATP/GTP-binding motif. The encoded protein interacts with alpha-synuclein in neuronal tissue and may play a role in the formation of cytoplasmic inclusions and neurodegeneration .
Beta-synuclein is suggested to be an inhibitor of alpha-synuclein aggregation, which occurs in neurodegenerative diseases such as Parkinson's disease. Thus, beta-synuclein may protect the central nervous system from the neurotoxic effects of alpha-synuclein and provide a novel treatment of neurodegenerative disorders. [9] [10]
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