Biology:XJB-5-131
XJB-5-131 is a mitochondria-targeted synthetic nitroxide antioxidant. The molecule is composed of two parts: a peptide isostere delivery component. Peptide was drawn from the cyclopeptide antibiotic gramicidin S, that targets the inner mitochondrial membrane. And the second part is a 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) nitroxide radical scavenger that disregards any oxygen species that are reactive.[1]
In a mouse model of Huntington's disease, XJB-5-131 has been seen to suppress somatic CAG repeat expansion by disturbing the toxic oxidation cycle. This process uses excision repair and mismatch repair pathway to promote oxidative DNA damage.[1] Therefore XJB-5-131 is seen to reduce oxidative damage to mitochondrial DNA, and to maintain mitochondrial DNA copy number.[2] XJB-5-131 also strongly protects against ferroptosis, a form of iron-dependent regulated cell death.[3]
References
- ↑ 1.0 1.1 Wipf P, Polyzos AA, McMurray CT. "XJB-5-131 is a suppressor of somatic instability and toxicity in Huntington's disease." Journal of Huntington's Disease. 2022; Pre-press December 2021.
- ↑ "Targeting of XJB-5-131 to mitochondria suppresses oxidative DNA damage and motor decline in a mouse model of Huntington's disease". Cell Reports 2 (5): 1137–42. November 2012. doi:10.1016/j.celrep.2012.10.001. PMID 23122961.
- ↑ "A Mitochondrial-Targeted Nitroxide Is a Potent Inhibitor of Ferroptosis". ACS Central Science 2 (9): 653–659. September 2016. doi:10.1021/acscentsci.6b00199. PMID 27725964.
Further reading
Sun W, Lv Z, Li W, et al. "XJB-5-131 protects chondrocytes from ferroptosis to alleviate osteoarthritis progression via restoring Pebp1 expression." Journal of Orthopaedic Translation. 2024;44:114–124
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