Mitochondrial dysfunction, a common cellular hallmark in both familial and sporadic forms of Parkinson's disease (PD), is assumed to play a significant role in pathologic development and progression of the disease. Teaghrelin, a unique bioactive compound in some oolong tea varieties, has been demonstrated to protect SH‐SY5Y cells against 1‐methyl‐4‐phenylpyridinium induced neurotoxicity by binding to the ghrelin receptor to activate the AMPK/SIRT1/PGC‐1α pathway. In this study, an animal model was established using a neurotoxin, 1‐methyl‐4phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), a byproduct of a prohibited drug, to evaluate the oral efficacy of teaghrelin on PD by monitoring motor dysfunction of mice in open field, pole, and bean walking tests. The results showed that MPTP‐induced motor dysfunction of mice was significantly attenuated by teaghrelin supplementation. Tyrosine hydroxylase and dopamine transporter protein were found reduced in the striatum and midbrain of MPTP‐treated mice, and significantly mitigated by teaghrelin supplementation. Furthermore, teaghrelin administration enhanced mitophagy and mitochondria biogenesis, which maintained cell homeostasis and prevented the accumulation of αSyn and apoptosis‐related proteins. It seemed that teaghrelin protected dopaminergic neurons in MPTP‐treated mice by increasing PINK1/Parkin‐mediated mitophagy and AMPK/SIRT1/PGC‐1α‐mediated mitochondria biogenesis, highlighting its potential therapeutic role in maintaining dopaminergic neurons function in PD. Mitochondrial dysfunction, a common cellular hallmark in both familial and sporadic forms of Parkinson's disease (PD), is assumed to play a significant role in pathologic development and progression of the disease. Teaghrelin, a unique bioactive compound in some oolong tea varieties, has been demonstrated to protect SH‐SY5Y cells against 1‐methyl‐4‐phenylpyridinium induced neurotoxicity by binding to the ghrelin receptor to activate the AMPK/SIRT1/PGC‐1α pathway. In this study, an animal model was established using a neurotoxin, 1‐methyl‐4phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), a byproduct of a prohibited drug, to evaluate the oral efficacy of teaghrelin on PD by monitoring motor dysfunction of mice in open field, pole, and bean walking tests. The results showed that MPTP‐induced motor dysfunction of mice was significantly attenuated by teaghrelin supplementation. Tyrosine hydroxylase and dopamine transporter protein were found reduced in the striatum and midbrain of MPTP‐treated mice, and significantly mitigated by teaghrelin supplementation. Furthermore, teaghrelin administration enhanced mitophagy and mitochondria biogenesis, which maintained cell homeostasis and prevented the accumulation of αSyn and apoptosis‐related proteins. It seemed that teaghrelin protected dopaminergic neurons in MPTP‐treated mice by increasing PINK1/Parkin‐mediated mitophagy and AMPK/SIRT1/PGC‐1α‐mediated mitochondria biogenesis, highlighting its potential therapeutic role in maintaining dopaminergic neurons function in PD.

中文翻译：

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Teaghrelin 通过促进 PINK1/Parkin 介导的线粒体自噬和 AMPK/SIRT1/PGC1-α 介导的线粒体生物发生来保护 MPTP 诱导的帕金森病动物模型中的多巴胺能神经元

线粒体功能障碍是帕金森病（PD）家族性和散发性的常见细胞标志，被认为在该疾病的病理发展和进展中发挥着重要作用。 Teaghrelin 是一些乌龙茶品种中的一种独特的生物活性化合物，已被证明可以通过与 ghrelin 受体结合激活 AMPK/SIRT1/PGC-1α 通路，保护 SH-SY5Y 细胞免受 1-甲基-4-苯基吡啶鎓诱导的神经毒性。本研究利用违禁药物的副产物——神经毒素1-甲基-4苯基-1,2,3,6-四氢吡啶（MPTP）建立动物模型，通过监测评估teaghrelin对PD的口服疗效。小鼠在旷场、杆子和豆子行走测试中的运动功能障碍。结果表明，补充茶瑞林可显着减弱 MPTP 引起的小鼠运动功能障碍。研究发现，经 MPTP 治疗的小鼠纹状体和中脑中的酪氨酸羟化酶和多巴胺转运蛋白减少，补充茶瑞林可显着减轻这种情况。此外，teaghrelin 的给药增强了线粒体自噬和线粒体生物合成，从而维持细胞稳态并防止 αSyn 和凋亡相关蛋白的积累。 Teaghrelin 似乎通过增加 PINK1/Parkin 介导的线粒体自噬和 AMPK/SIRT1/PGC-1α 介导的线粒体生物合成来保护 MPTP 治疗小鼠的多巴胺能神经元，这凸显了其在维持 PD 多巴胺能神经元功能方面的潜在治疗作用。线粒体功能障碍是帕金森病（PD）家族性和散发性的常见细胞标志，被认为在该疾病的病理发展和进展中发挥着重要作用。 Teaghrelin 是一些乌龙茶品种中的一种独特的生物活性化合物，已被证明可以通过与 ghrelin 受体结合激活 AMPK/SIRT1/PGC-1α 通路，保护 SH-SY5Y 细胞免受 1-甲基-4-苯基吡啶鎓诱导的神经毒性。本研究利用违禁药物的副产物——神经毒素1-甲基-4苯基-1,2,3,6-四氢吡啶（MPTP）建立动物模型，通过监测评估teaghrelin对PD的口服疗效。小鼠在旷场、杆子和豆子行走测试中的运动功能障碍。结果表明，补充茶瑞林可显着减弱 MPTP 引起的小鼠运动功能障碍。研究发现，经 MPTP 治疗的小鼠纹状体和中脑中的酪氨酸羟化酶和多巴胺转运蛋白减少，补充茶瑞林可显着减轻这种情况。此外，teaghrelin 的给药增强了线粒体自噬和线粒体生物合成，从而维持细胞稳态并防止 αSyn 和凋亡相关蛋白的积累。 Teaghrelin 似乎通过增加 PINK1/Parkin 介导的线粒体自噬和 AMPK/SIRT1/PGC-1α 介导的线粒体生物合成来保护 MPTP 治疗小鼠的多巴胺能神经元，强调其在维持帕金森病多巴胺能神经元功能方面的潜在治疗作用。