Department of Clinical Neuroscience (CNS), J5:20 Bioclinicum, Karolinska University Hospital, Stockholm, Sweden.
Curr Opin Neurol. 2021 Aug 1;34(4):578-588. doi: 10.1097/WCO.0000000000000959.
To provide an update on the role of Ataxin-2 gene (ATXN2) in health and neurological diseases.
There is a growing complexity emerging on the role of ATXN2 and its variants in association with SCA2 and several other neurological diseases. Polymorphisms and intermediate alleles in ATXN2 establish this gene as a powerful modulator of neurological diseases including lethal neurodegenerative conditions such as motor neuron disease, spinocerebellar ataxia 3 (SCA3), and peripheral nerve disease such as familial amyloidosis polyneuropathy. This role is in fact far wider than the previously described for polymorphism in the prion protein (PRNP) gene. Positive data from antisense oligo therapy in a murine model of SCA2 suggest that similar approaches may be feasible in humans SCA2 patients.
ATXN2 is one of the few genes where a single gene causes several diseases and/or modifies several and disparate neurological disorders. Hence, understanding mutagenesis, genetic variants, and biological functions will help managing SCA2, and several human diseases connected with dysfunctional pathways in the brain, innate immunity, autophagy, cellular, lipid, and RNA metabolism.
综述目的：介绍 Ataxin-2 基因（ATXN2）在健康和神经疾病中的作用的最新研究进展。
新发现：ATXN2 及其变体与 SCA2 和其他几种神经疾病的关联作用，其复杂性日益增加。ATXN2 中的多态性和中间等位基因使该基因成为包括致命神经退行性疾病（如运动神经元病、脊髓小脑共济失调 3 型（SCA3）和周围神经病（如家族性淀粉样多神经病）在内的多种神经疾病的有力调节因子。这种作用实际上比先前描述的朊病毒蛋白（PRNP）基因中的多态性更为广泛。SCA2 小鼠模型中的反义寡核苷酸治疗的阳性数据表明，类似的方法在 SCA2 患者中可能是可行的。
总结：ATXN2 是少数几个单一基因导致多种疾病和/或修饰多种不同神经疾病的基因之一。因此，了解突变、遗传变异和生物学功能将有助于治疗 SCA2 以及与大脑功能障碍途径、先天免疫、自噬、细胞、脂质和 RNA 代谢相关的几种人类疾病。
