a Neurodegenerative Disease Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs , University of Bari "Aldo Moro" , Bari , Italy.
b Department of Clinical Research in Neurology, Center for Neurodegenerative Diseases and the Aging Brain , University of Bari "Aldo Moro", "Pia Fondazione Cardinale G. Panico" , Lecce , Italy.
Expert Rev Neurother. 2019 May;19(5):397-408. doi: 10.1080/14737175.2019.1606715. Epub 2019 Apr 25.
Tauopathies are heterogeneous clinicopathological entities characterized by abnormal neuronal and/or glial inclusions of the microtubule-binding protein tau. Primary tauopathies considered to be diseases correspond to a major class of frontotemporal lobar degeneration (FTLD) neuropathology (FTLD-Tau), including several forms of frontotemporal dementia (FTD) clinical syndromes. Little progress has been made in the past 20 years in developing effective disease-modifying drugs for primary tauopathies and available symptomatic treatments have limited efficacy. Areas covered: Potential disease-modifying drugs in clinical development to slow neuropathological progression of primary tauopathies. Expert opinion: Since the underlying pathology of primary tauopathies consists of abnormal tau protein aggregates, treatments are being developed to interfere with the aggregation process or to promote the clearance of this protein. Unfortunately, disease-modifying treatments remain years away as demonstrated by the recent negative Phase III findings of a tau aggregation inhibitor (LMTM) for treating the behavioral variant of FTD. Further evidence will come from ongoing Phase I/II trials on novel drugs and immunotherapeutics with various targets - prevention of deposition or removal of tau aggregates, inhibition of tau phosphorylation/acetylation, modulation of O-GlcNAcylation, activation of autophagy or ubiquitin-proteasome system pathways, and rescue of selected tau loss of function or suppression of tau gene expression.
tau 病是一组异质性临床病理实体，其特征为微管结合蛋白 tau 的神经元和/或神经胶质异常包涵体。原发性 tau 病被认为是疾病，对应于额颞叶变性（FTLD）神经病理学（FTLD-Tau）的主要类别之一，包括几种额颞痴呆（FTD）临床综合征。在过去的 20 年中，在开发用于原发性 tau 病的有效疾病修饰药物方面几乎没有取得进展，而现有的对症治疗方法疗效有限。涵盖领域：正在开发用于减缓原发性 tau 病神经病理学进展的潜在疾病修饰药物。专家意见：由于原发性 tau 病的潜在病理学由异常 tau 蛋白聚集组成，因此正在开发治疗方法以干扰聚集过程或促进这种蛋白的清除。不幸的是，正如最近治疗额颞叶痴呆行为变异型的 tau 聚集抑制剂（LMTM）的 III 期阴性研究结果所示，疾病修饰治疗仍遥遥无期。来自正在进行的针对各种靶点的新型药物和免疫疗法的 I/II 期试验将提供进一步的证据——预防 tau 聚集物的沉积或清除、抑制 tau 磷酸化/乙酰化、调节 O-GlcNAcylation、激活自噬或泛素-蛋白酶体系统途径，以及挽救选定的 tau 功能丧失或抑制 tau 基因表达。
