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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]
Positive α-Synuclein staining of a Lewy body from a patient who had Parkinson's disease. 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 ...
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 .
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 major filamentous component of Papp-Lantos bodies, glial and neuronal cytoplasmic inclusions, is alpha-synuclein. [32] Mutations in this substance may play a role in the disease. [33] The conformation of the alpha-synuclein is different from that of alpha-synuclein in Lewy bodies. [3] The disease probably starts with an oligodendrogliopathy ...
alpha-synuclein: can aggregate to form insoluble fibrils in pathological conditions characterized by Lewy bodies, such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Alpha-synuclein is the primary structural component of Lewy body fibrils.
A brain tissue with Lewy bodies. The first major proposed cause of neuronal death in Parkinson's disease is the bundling, or oligomerization, of proteins.The protein alpha-synuclein has increased presence in the brains of Parkinson's Disease patients and, as α-synuclein is insoluble, it aggregates to form Lewy bodies (shown to left) in neurons.
Under pathological conditions in PD, alpha-synuclein undergoes a conformational change, resulting in a misfolded insoluble protein that aggregates into beta-sheets and forms protein inclusions called Lewy Bodies. [4] [3] [6] [8] [9] Aggregated alpha-synuclein loses its ability to bind at the membrane, disrupting cellular processes and synaptic ...