S-52, a novel nootropic compound, protects against β-amyloid induced neuronal injury by attenuating mitochondrial dysfunction.
Accumulating evidence suggests that β-amyloid (Aβ)-induced oxidative DNA damage and mitochondrial dysfunction may initiate and contribute to the progression of Alzheimer's disease (AD). This study evaluated the neuroprotective effects of S-52, a novel nootropic compound, on Aβ-induced mitochondrial failure. In an established paradigm of moderate cellular injury induced by Aβ, S-52 was observed to attenuate the toxicity of Aβ to energy metabolism, mitochondrial membrane structure, and key enzymes in the electron transport chain and tricarboxylic acid cycle. In addition, S-52 also effectively inhibited reactive oxygen species accumulation dose dependently not only in Aβ-harmed cells but also in unharmed, normal cells. The role of S-52 as a scavenger of free radicals is involved in the antioxidative effect of this compound. The beneficial effects on mitochondria and oxidative stress extend the neuroprotective effects of S-52. The present study provides crucial information for better understanding the beneficial profiles of this compound and discovering novel potential drug candidates for AD therapy.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
Xin
X
Gao
Chun Yan
CY
Zheng
Guo Wei
GW
Qin
Xi Can
XC
Tang
Hai Yan
HY
Zhang
D000255:Adenosine Triphosphate / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004579:Electron Transport / Q000187:drug effects; D005470:Fluorometry; D016166:Free Radical Scavengers / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D009019:Morphinans / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018697:Nootropic Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016166:Free Radical Scavengers; D009019:Morphinans; D018697:Nootropic Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C577074:S-52 compound; C074636:amyloid beta-protein (25-35); D013481:Superoxides; D017665:Hydroxyl Radical; D000255:Adenosine Triphosphate