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应用现有知识和资源来缓解家族性和散发性神经退行性疾病。

Applying available knowledge and resources to alleviate familial and sporadic neurodegenerative disorders.

机构信息

Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

出版信息

Prog Mol Biol Transl Sci. 2021;177:91-107. doi: 10.1016/bs.pmbts.2020.09.001. Epub 2020 Oct 20.

Abstract

Here I present the scientific rationale and implementation strategies for elimination of early-onset neurodegenerative disorders (EONDD) from future generations, and for risk reduction and treatments for the more common late-onset neurodegenerative disorders (LONDD). Young adults with a family history of an EONDD should be educated on the genetics and familial burden of EONDD. They can then be genotyped and, if positive for the mutation, counseled as to how they can ensure that none of their children will be affected by choosing either adoption or in vitro fertilization and preimplantation genetic testing. LONDD risk reduction will require education of physicians and patients on the benefits of regular intermittent bioenergetic and cognitive challenges (exercise, intermittent fasting, intellectual challenges and social engagement) for brain health, and on specific risk-reduction regimens. Regulations will be required to counteract the disease-promoting mercenary practices of the processed food and pharmaceutical industries. Clinical trials of pharmacological interventions should shift to small trials of agents that substantially mimic mechanisms of action of exercise and intermittent fasting to bolster neuronal bioenergetics and stress resistance.

摘要

在此,我提出了从未来几代人中消除早发性神经退行性疾病(EONDD)的科学依据和实施策略,以及降低更常见的晚发性神经退行性疾病(LONDD)风险和治疗方法。有 EONDD 家族史的年轻成年人应接受有关 EONDD 的遗传学和家族负担的教育。然后,他们可以进行基因分型,如果携带突变,则可以就如何通过选择收养或体外受精和胚胎植入前基因检测来确保他们的孩子不受影响进行咨询。降低 LONDD 风险需要教育医生和患者定期进行间歇性生物能量和认知挑战(运动、间歇性禁食、智力挑战和社交参与)对大脑健康的益处,以及特定的降低风险方案。需要制定法规来抵制加工食品和制药行业促进疾病的唯利是图的做法。药物干预临床试验应转向模仿运动和间歇性禁食作用机制的药物的小型试验,以增强神经元的生物能量和抗应激能力。

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