Huntington disease (HD) is a neurodegenerative disorder produced by an expansion of CAG repeats in the HTT gene. Patients of HD show involuntary movements, cognitive decline and psychiatric impairment. People carrying abnormally long expansions of CAGs (more than 35 CAG repeats) produce mutant huntingtin (mHtt), which encodes tracks of polyglutamines (polyQs). These polyQs make the protein prone to aggregate and cause it to acquire a toxic gain of function. Principally affecting the frontal cortex and the striatum, mHtt disrupts many cellular functions. In addition, this protein is expressed ubiquitously, and some reports show that many other cell types are affected by the toxicity of mHtt. Several studies reported that metformin, a widely-used anti-diabetic drug, is neuroprotective in models of HD. Here, we provide a review of the benefits of this substance to treat HD. Metformin is a pleiotropic drug, modulating different targets such as AMPK, insulin signalling and many others. These molecules regulate autophagy, chaperone expression, and more, which in turn reduce mHtt toxicity. Moreover, metformin alters gut microbiome and its metabolic processes. The study of potential targets, interactions between the drug, host and microbiome, or genomic and pharmacogenomic approaches may allow us to design personalised medicine to treat HD.

亨廷顿病 (HD) 是一种神经退行性疾病，由HTT中 CAG 重复序列的扩展产生基因。HD患者表现出不自主运动、认知能力下降和精神障碍。携带异常长的 CAG 扩展（超过 35 个 CAG 重复）的人会产生突变亨廷顿蛋白 (mHtt)，它编码多聚谷氨酰胺 (polyQs) 的轨迹。这些 polyQ 使蛋白质易于聚集并使其获得有毒的功能增益。mHtt 主要影响额叶皮层和纹状体，会破坏许多细胞功能。此外，这种蛋白质普遍表达，一些报告显示许多其他细胞类型受到 mHtt 毒性的影响。几项研究报告称，二甲双胍是一种广泛使用的抗糖尿病药物，在 HD 模型中具有神经保护作用。在这里，我们回顾了这种物质治疗 HD 的益处。二甲双胍是一种多效性药物，可调节不同的靶点，如 AMPK、胰岛素信号和许多其他。这些分子调节自噬、伴侣蛋白表达等，从而降低 mHtt 毒性。此外，二甲双胍会改变肠道微生物组及其代谢过程。潜在靶点的研究、药物、宿主和微生物组之间的相互作用，或基因组和药物基因组学方法的研究，可能使我们能够设计个性化的药物来治疗 HD。