3-nitrotyrosine-modified amyloid-beta (3NTyr-Aβ) (3NTyr-Aβ)

3-nitrotyrosine-modified amyloid-beta (3NTyr-Aβ) is a pathological post-translational modification of the amyloid-beta peptide, occurring primarily at the tyrosine residue at position 10 (Tyr10) [Kummer et al., 2011]. This modification is driven by reactive nitrogen species produced during chronic neuroinflammation and oxidative stress, which are hallmarks of Alzheimer's disease [Al-Azzawi et al., 2020]. 3NTyr-Aβ monomers are characterized by an increased propensity to misfold and aggregate compared to their unmodified counterparts, functioning as potent "seeds" that accelerate the aggregation of wild-type amyloid-beta into toxic oligomers and insoluble plaques [Guivernau et al., 2016]. Because of its specific role in initiating and exacerbating amyloid pathology, 3NTyr-Aβ is considered a high-priority therapeutic target for disease-modifying treatments. Experimental treatments, such as monoclonal antibodies (e.g., clone 9D1), are designed to selectively bind and neutralize these nitrated species to halt the seeding process and facilitate the clearance of toxic aggregates [Kummer et al., 2011]. By focusing on this specific modified species, researchers hope to achieve higher selectivity and potentially reduce the side effects associated with broad amyloid-beta clearance, such as ARIA [Sperling et al., 2011].

Other names

Nitrated amyloid-beta3-nitrotyrosine-10 amyloid-beta3NTyr10-AbetanAbeta

Passive immunotherapy targeting nitrated amyloid-beta monomers to prevent the seeding and propagation of amyloid-beta aggregates [Kummer et al., 2011; Al-Azzawi et al., 2020].