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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 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]
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]
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 ...
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The protein encoded by this gene is highly homologous to alpha-synuclein. These proteins are abundantly expressed in the brain and putatively inhibit phospholipase D2 selectively. The encoded protein, which may play a role in neuronal plasticity, is abundant in neurofibrillary lesions of patients with Alzheimer's disease .
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 .