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Tropisetron and its targets in Alzheimer's disease

机译：Tropisetron及其在阿尔茨海默氏病中的靶标

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Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. Despite this, there are no drugs for preventing the onset of AD. Preclinical studies suggest that the interaction between amyloid-beta peptides (A beta) and the alpha 7 nicotinic acetylcholine receptor (alpha 7 nAChR) plays a key role in AD pathology, and that alpha 7 nAChR agonists could act as potential therapeutic drugs for AD. A recent study demonstrated that tropisetron, a potent alpha 7 nAChR agonist and serotonin 5-hydroxytryptamine3 receptor antagonist, also bound to the ectodomain of amyloid precursor protein. Furthermore, tropisetron promoted greater improvements in memory than current AD therapeutic drugs, such as memantine and donepezil. Positron emission tomography studies detected A beta deposition and inflammation in the brains of subjects with amnestic mild cognitive impairment (MCI) before the onset of AD. Given the role of alpha 7 nAChR in A beta deposition and inflammation, tropisetron represents an attractive potential therapeutic drug to delay or prevent MCI and AD. Additionally as this drug is used internationally to treat chemotherapy-induced emesis, its safety record is already known.
机译：阿尔茨海默氏病（AD）是最常见的年龄相关性神经退行性疾病。尽管如此，没有药物可以预防AD的发作。临床前研究表明，淀粉样蛋白-β肽（A beta）和α7烟碱型乙酰胆碱受体（α7nAChR）之间的相互作用在AD病理学中起着关键作用，而α7nAChR激动剂可以作为AD的潜在治疗药物。最近的一项研究表明，tropisetron是一种强效的α7 nAChR激动剂和5-羟色胺5-羟色胺3受体拮抗剂，也与淀粉样前体蛋白的胞外域结合。此外，与当前的美金刚和多奈哌齐等AD治疗药物相比，托吡司琼在记忆方面的改善更大。正电子发射断层扫描研究发现，在AD发作之前，患有轻度认知障碍（MCI）的受试者的大脑中存在β沉积和炎症。鉴于alpha 7 nAChR在A beta沉积和炎症中的作用，托吡司琼是一种有吸引力的潜在治疗药物，可延迟或预防MCI和AD。另外，由于该药物在国际上用于治疗化学疗法引起的呕吐，因此其安全性记录是已知的。

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