Neuroinflammation and mitochondrial function are crucial for neuronal function and survival. SS-31 is a novel mitochondria-targeted peptide antioxidant that reduces mitochondrial reactive oxygen species production, increases ATP generation, protects the integrity of mitochondrial cristae and the mitochondrial respiratory chain, and reduces inflammatory responses. Exploring novel SS-31 derivatives is important for the treatment of neurodegenerative diseases. In this study, nineteen SS-31 derived peptides (5a-5s) were synthesized. Through cellular activity screening, we discovered that 5f and 5g exhibited significantly greater anti-inflammatory activity compared to SS-31, reducing LPS-induced TNF-alpha levels by 43% and 45%, respectively, at a concentration of 10 mu M. Furthermore, treatment with 50 nM of 5f and 5g increased ATP synthesis by 42% and 41% in rotenone-induced HT22 cells and attenuated mitochondrial ROS production by preserving mitochondrial integrity. These findings demonstrate their direct protective effects on neuronal mitochondria. This work highlights the potential of 5f and 5g in the treatment of neurodegenerative diseases associated with inflammation and mitochondrial damage, offering a promising therapeutic avenue for mitochondrial-related conditions such as Alzheimer''s disease.
[1]Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Jinan 250012, Shandong, Peoples R China.
[2]Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Qingdao Key Lab Mitochondrial Med, Qingdao 266103, Peoples R China.
[3]Shandong Univ, Qilu Hosp Qingdao, Dept Med Expt Ctr, Dept Anorectal Ctr, Qingdao 266035, Shandong, Peoples R China.
(8.0+极速模式)