Neuroprotective Effects of Kinsenoside in an iPSC-derived ALS Model

doi:10.3870/j.issn.1672-0741.26.03.018

Abstract

Abstract: Objective To investigate the therapeutic effects and mechanisms of kinsenoside in amyotrophic lateral sclerosis(ALS)using an induced pluripotent stem cell(iPSC)-derived motor neuron model.Methods Motor neurons differentiated from SOD1^D90A mutant iPSCs were used as the ALS model.Isogenic motor neurons corrected to wild-type SOD1(SOD1^D90D)via TALEN technology served as controls.The safe concentration range and optimal treatment concentration of kinsenoside in the ALS cell model were determined.Morphological assessments were then conducted to evaluate its ameliorative effects on axonal degeneration phenotypes,and changes in cellular energy metabolism were measured.Expression levels of KEAP1/Nrf2,key molecules in the oxidative stress pathway,were determined by molecular biology techniques,and potential downstream targets were investigated.Results In the ALS cell model treated with kinseoside,pathological phenotypes were significantly ameliorated,as evidenced by reduced axonal swelling and increased axonal length.Meanwhile,abnormal mitochondrial aggregation within swollen axons was markedly alleviated,intracellular ATP levels were significantly elevated,and lactate content in the culture supernatant was reduced.Mechanistic studies revealed that after kinseoside treatment,KEAP1 protein levels decreased while Nrf2 protein levels increased in ALS model cells.TheqRT-PCR results confirmed that kinseoside reversed the mRNA transcription levels of mitochondrial fusion-related genes MFN2 and OPA1,as well as the mitophagy-related gene PINK1.Conclusion Kinsenoside may ameliorate the pathological damage of ALS motor neuron model by regulating the KEAP1/Nrf2 oxidative stress pathway and the expression of genes related to mitochondrial fusion and mitophagy.

Key words: amyotrophic lateral sclerosis, motor neuron, kinsenoside, pharmacotherapy, mitochondrial function

CLC Number:

R746.4

Huang Yunjie, Li Xiangling, Zhou Qiuzhi, et al. Neuroprotective Effects of Kinsenoside in an iPSC-derived ALS Model[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(4): 457-464.

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