Authors: Dr. Adi Lahiani , Adel Hidmi , Joshua Katzhendler, Prof Philip Lazarovici, Ephraim Yavin
Antioxidants such as α-Lipoic acid and Tempol are known to confer neuroprotection towards ischemic insults and therefore considered for therapy in stroke and traumatic brain injury. The aim of the present study was to screen and characterize a more efficacious molecule with neuroprotective activity, from several groups of synthetic compounds classified as NO donors, α-LA linked to alkyl or PEG carrier and bifunctional compounds, based on α-LA linked to NO donors. Screening of several neuroprotective compounds using the PC12 cell model exposed to oxygen and glucose deprivation (OGD) has identified a neuroprotective compound (AD3) composed of both NO donor and α-LA moieties. Its neuroprotection index (NP-Index) of 0.36 is similar to that of Rasagiline, a MAO B inhibitor, and vitamin C both known for neuroprotection in ischemic models. Further development and investigation of the mechanism of action of AD3 may provide a superior antioxidant neuroprotective drug for ischemic diseases.
Keywords: α-LA, α- Lipoic acid; PEG, polyethylene glycol; LDH, lactate dehydrogenase; NP-Index, neuroprotective index; OGD, oxygen and glucose deprivation; PC12, pheochromocytoma cells; Tempol,4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl.