Singh Himanshi, Das Asmita, Khan Mohammad Moshahid, Pourmotabbed Tayebeh
Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA; Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Delhi, India; Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Delhi, India.
Neural Regen Res. 2024 May;19(5):1020-1026. doi: 10.4103/1673-5374.385288.
Tauopathies are a group of neurological disorders, including Alzheimer's disease and frontotemporal dementia, which involve progressive neurodegeneration, cognitive deficits, and aberrant tau protein accumulation. The development of tauopathies cannot currently be stopped or slowed down by treatment measures. Given the significant contribution of tau burden in primary tauopathies and the strong association between pathogenic tau accumulation and cognitive deficits, there has been a lot of interest in creating therapies that can alleviate tau pathology and render neuroprotective effects. Recently, small molecules, immunotherapies, and gene therapy have been used to reduce the pathological tau burden and prevent neurodegeneration in animal models of tauopathies. However, the major pitfall of the current therapeutic approach is the difficulty of drugs and gene-targeting modalities to cross the blood-brain barrier and their unintended side effects. In this review, the current therapeutic strategies used for tauopathies including the use of oligonucleotide-based gene therapy approaches that have shown a promising result for the treatment of tauopathies and Alzheimer's disease in preclinical animal models, have been discussed.
tau蛋白病是一组神经疾病，包括阿尔茨海默病和额颞叶痴呆，其涉及进行性神经退行性变、认知缺陷以及异常的tau蛋白积累。目前，治疗措施无法阻止或减缓tau蛋白病的发展。鉴于tau蛋白负荷在原发性tau蛋白病中的重要作用，以及致病性tau蛋白积累与认知缺陷之间的紧密联系，人们对开发能够减轻tau蛋白病理并产生神经保护作用的疗法产生了浓厚兴趣。最近，小分子、免疫疗法和基因疗法已被用于减少tau蛋白病动物模型中的病理性tau蛋白负荷并预防神经退行性变。然而，当前治疗方法的主要缺陷在于药物和基因靶向方式难以穿过血脑屏障以及它们意想不到的副作用。在这篇综述中，讨论了目前用于tau蛋白病的治疗策略，包括基于寡核苷酸的基因治疗方法，这些方法在临床前动物模型中已显示出对治疗tau蛋白病和阿尔茨海默病有前景的结果。
