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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 proteins alpha-Synuclein (α-Syn) and DJ-1 have been shown to promote MAM function interaction between the ER and the mitochondria. The wild-type gene that codes for α-Syn promotes the physical junction between ER and mitochondria by binding to the lipid raft regions of the MAM.
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]
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.
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 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.
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.