Recent studies show at dysregulation of redox signaling and sulfhydryl homeostasis likely contributes to onset/progression of neurodegeneration. S-Glutathionylation of key enzymes and proteins has been implicated in neurodegenerative diseases. However, the exact roles of sulfhydryl homeostasis and protein S-glutathionylation in the pathology of these diseases are not fully understood. This field is evolving and much remains to be explored.
The inability of GSSG to pass through cell membrane and a lack of effective method to deliver it into cells has hampered our ability to investigate the role of GSSG in its normal and abnormal cellular functions. Liposomes as one of the most effective and widely used delivery systems have been employed to aid the delivery of bioactive agents through various biological membrane and biological barriers including blood-brain barrier(BBB). GSSG liposomes reported here are the first method that delivers specifically GSSG into cells. We demonstrated that different concentrations of GSSG liposomes can be conveniently prepared through the use of a PBS solution containing different concentrations of GSSG; providing us the ability to manipulate intracellular GSSG concentra tion. The data from protein S-glutathionylation confirmed that GSSG delivered to cells by GSSG liposomes were functionally ef fective. Further, cell viability study showed that GSSG liposomes exhibited no significant cytotoxicity. Therefore, the GSSG liposomes can serve as a valuable tool in studying the role of GSSG in GSSG-associated cellular function and dysfunction. These studies can help identify approaches to prevent GSSG-associated diseases and potentially provide effective treatments. GSSG liposomes can also undoubtedly help the investigation of the role of protein S-glutathionylation in various cellular regulatory mechanisms.