Nitrated alpha-synuclein (n-alpha-syn)

Nitrated alpha-synuclein is a pathologically modified form of the alpha-synuclein protein, characterized by the addition of nitro groups to tyrosine residues, particularly Tyr39, Tyr125, Tyr133, and Tyr136, under conditions of oxidative stress (Giasson et al., 2000, Science). This post-translational modification is a hallmark of synucleinopathies, including Parkinson's disease and Multiple System Atrophy, where it promotes the formation of stable, toxic oligomers and insoluble fibrils (Souza et al., 2000, Journal of Biological Chemistry). Unlike the native protein, nitrated alpha-synuclein is highly pro-inflammatory and can trigger microglial activation, leading to the progressive death of dopaminergic neurons (Prasad et al., 2023, Frontiers in Neuroscience). It is considered a potent therapeutic target because it is specifically associated with diseased tissue and is largely absent in healthy brains, allowing for high selectivity (Shults, 2006, Archives of Neurology). Current therapeutic strategies involve the development of monoclonal antibodies, such as PV-1950, designed to recognize and clear these nitrated species without interfering with the physiological functions of native alpha-synuclein. These immunotherapies aim to halt the cell-to-cell transmission of toxic aggregates and reduce neuroinflammation in the central nervous system (Danielson et al., 2009, PLoS ONE).

Other names

3-nitrotyrosine alpha-synucleinNitrated SNCAn-alpha-synucleinNitrated alpha-synuclein (n-alpha-syn)

Selective clearance of pathological protein aggregates via passive immunotherapy and inhibition of seeding/propagation.