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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 .
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]
Liquid-liquid phase separation (LLPS) is well defined in the Biomolecular condensate page. LLPS databases cover different aspects of LLPS phenomena, ranging from cellular location of the Membraneless Organelles (MLOs) to the role of a particular protein/region forming the condensate state.
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]
Beta-synuclein is a protein that in humans is encoded by the SNCB gene. [5] [6] [7] 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.
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.
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