Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis

• DOI: 10.1016/j.apsb.2022.07.019
• Publication Date: 2022-08-10T19:32:58Z
• Authors: Yujun Zhou; Jingshu Tang; Jiaqi Lan; Yong Zhang; Hongyue Wang; Qiuyu Chen; Yuying Kang; Yang Sun; Xinhong Feng; Lei Wu; Hongtao Jin; Shizhong Chen; Ying Peng
• Keywords: Honokiol

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute the progression of ALS, including neuronal oxidative stress mitochondrial dysfunction. Honokiol (HNK) has been reported exert therapeutic effects in several neurologic models ischemia stroke, Alzheimer's Parkinson's disease. Here we found that honokiol also exhibited protective ALS vitro vivo. improved viability NSC-34 neuron-like cells expressed mutant G93A SOD1 proteins (SOD1-G93A for short). Mechanistical studies revealed alleviated cellular by enhancing glutathione (GSH) synthesis activating nuclear factor erythroid 2-related 2 (NRF2)-antioxidant response element (ARE) pathway. Also, function morphology via fine-tuning dynamics SOD1-G93A cells. Importantly, extended lifespan transgenic mice function. The improvement antioxidant capacity was further confirmed spinal cord gastrocnemius muscle mice. Overall, showed promising preclinical potential as multiple target drug treatment.