Gastrodin ameliorates synaptic impairment, mitochondrial dysfunction and oxidative stress in N2a/APP cells

Tang, Zhi; Peng, Yaqian; Jiang, Yi; Wang, Li; Guo, Min; Chen, Zhuyi; Luo, Chao; Zhang, Ting; Xiao, Yan; Ni, Ruiqing; Qi, Xiaolan

doi:10.1016/j.bbrc.2024.150127

Cited by 4 publications

References 80 publications

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The role of gastrodin in the management of CNS‐related diseases: Underlying mechanisms to therapeutic perspectives

He,

Chen,

Yang

et al. 2024

Phytotherapy Research

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Central nervous system (CNS)‐related diseases have a high mortality rate, are a serious threat to physical and mental health, and have always been an important area of research. Gastrodin, the main active metabolite of Gastrodia elata Blume, used in Chinese medicine and food, has a wide range of pharmacological effects, mostly related to CNS disorders. This review aims to systematically summarize and discuss the effects and underlying mechanisms of gastrodin in the treatment of CNS diseases, and to assess its potential for further development as a lead drug in both biomedicine and traditional Chinese medicine. Studies on the pharmacological effects of gastrodin on the CNS indicate that it may exert anti‐neurodegenerative, cerebrovascular protective, and ameliorative effects on diabetic encephalopathy, perioperative neurocognitive dysfunction, epilepsy, Tourette's syndrome, depression and anxiety, and sleep disorders through various mechanisms. To date, 110 gastrodin products have been approved for clinical use, but further multicenter clinical case–control studies are relatively scarce. Preclinical studies have confirmed that gastrodin can be used to treat CNS‐related disorders. However, important concerns need to be addressed in the context of likely non‐specific, assay interfering effects when gastrodin is studied using in vitro and in silico approaches, calling for a systematic assessment of the evidence to date. High‐quality clinical trials should have priority to evaluate the therapeutic safety and clinical efficacy of gastrodin. Further experimental research using appropriate in vivo models is also needed, focusing on neurodegenerative diseases, cerebral ischemic and hypoxic diseases, brain damage caused by methamphetamine or heavy metals, and epilepsy.

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The role of gastrodin in the management of CNS‐related diseases: Underlying mechanisms to therapeutic perspectives

He,

Chen,

Yang

et al. 2024

Phytotherapy Research

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Myricetin ameliorates cognitive impairment in 3×Tg Alzheimer’s disease mice by regulating oxidative stress and tau hyperphosphorylation

Wang,

Tang,

et al. 2024

Biomedicine & Pharmacotherapy

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mTOR inhibition alleviated tau phosphorylation-induced mitochondrial impairment, oxidative stress, and cognitive impairment

Tang,

Guo,

Ding

et al. 2024

Preprint

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Aim: Hyperphosphorylated tau plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Whether mammalian target of rapamycin (mTOR) directly interacts with the Tau protein at Ser214, Ser356 and Thr231 is not clear. This study aimed to investigate whether mTOR-regulated tau phosphorylation disrupts mitochondrial dynamics and function and whether rapamycin, an mTOR inhibitor, can modulate tau phosphorylation levels and attenuate AD-related alterations. Methods: Adeno-associated virus (AAV) vectors were used to intracranially deliver the TauS214E/T231E/S356E (Tau3E) variant into 2-month-old C57BL/6 mice. The mice were intraperitoneally administered the mTOR inhibitor rapamycin for one week, followed by assessment via the Morris water maze test. Western blot analysis, immunofluorescence staining, and flow cytometry were employed to measure the expression levels of mTOR, p70S6K, and tau; mitochondrial dynamics; and reactive oxygen species (ROS) in HT22 cells and a mouse model overexpressing Tau3E, as well as in postmortem brain tissues from AD patients. Results: p-mTORS2448 colocalized with p-TauSer214, p-TauSer356, and p-TauThr231 in the hippocampal CA3 region of AD patients. HT22 cells and C57BL/6 mice overexpressing Tau3E presented elevated levels of p-mTOR, downstream target p-p70S6K, and ROS production; mitochondrial fragmentation; and p-TauSer214, p-TauSer356, and p-TauThr231. Rapamycin treatment partially mitigated the cognitive and molecular alterations in Tau3E mice. Conclusion: This study revealed a causal link between Tau phosphorylation at Ser214, Ser356, and p-Thr231 and mTOR upregulation and downstream impairments in ROS, mitochondrial dysfunction and cognitive function. Treatment using mTOR inhibitor rapamycin (i.p.) can alleviate impairment, reduce p-Tau and restore mitochondrial homeostasis, neuronal loss and cognitive impairment in mice.

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Gastrodin ameliorates synaptic impairment, mitochondrial dysfunction and oxidative stress in N2a/APP cells

Cited by 4 publications

References 80 publications

The role of gastrodin in the management of CNS‐related diseases: Underlying mechanisms to therapeutic perspectives

The role of gastrodin in the management of CNS‐related diseases: Underlying mechanisms to therapeutic perspectives

Myricetin ameliorates cognitive impairment in 3×Tg Alzheimer’s disease mice by regulating oxidative stress and tau hyperphosphorylation

mTOR inhibition alleviated tau phosphorylation-induced mitochondrial impairment, oxidative stress, and cognitive impairment

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