Biophysical elucidation of neural network and chemical regeneration of neural tissue

Boosting the enzymatic activity of CxxC motif-containing PDI family members

“…Loss-of-function of PDIs can thus result in severe diseases, such as neurodegeneration and diabetes. Notably, redox active site dysfunction in PDIA1 and PDIA6 CxxC motifs induced by posttranslational chemical modifications has been observed in AD 6 , suggesting that misfolding-related pathologies can be ameliorated using redox chemistry 7 . Extracellular PDIs are promising targets for thrombosis-related and tumor diseases owing to the upregulation of PDIs expression level, and several PDIs inhibitors, such as 16F16, bisphenol A, PACMA31, LOC14, and piericone, have been reported [8][9][10][11][12] .…”

“…Therefore, pathological redox imbalances can be caused by uncontrolled oxidation (e.g., excessive amount of reactive oxygen species) or reduction (e.g., hypo-oxidation in the ER contributing to the etiology of misfolding diseases such as diabetes and AD 24 ). Further, dysfunction of PDI family members is known to cause pathological diseases such as neurodegeneration and diabetes 4,7 . Therefore, chemically controlling PDI family as ER-resident redox enzymes is crucial.…”

“…Notably, redox active site dysfunction in PDIA1 and PDIA6 CxxC motifs induced by posttranslational chemical modifications has been observed in AD, 6 suggesting that misfolding-related pathologies can be ameliorated using redox chemistry. 7 Extracellular PDIs are promising targets for thrombosis-related and tumor diseases owing to the upregulation of the PDI expression level, and several PDI inhibitors, such as 16F16, bisphenol A, PACMA31, LOC14, and piericone, have been reported. [8][9][10][11][12] Many of these antagonists abolish the PDI catalytic activity by acting on cysteines within CxxC motifs or by competitively inhibiting its function by binding to its substrate-binding pocket.…”

“…Further, dysfunction of PDI family members is known to cause pathological diseases such as neurodegeneration and diabetes. 4,7 Therefore, chemically controlling the PDI family as ER-resident redox enzymes is crucial.…”