Lozupone Madia, Dibello Vittorio, Daniele Antonio, Solfrizzi Vincenzo, Resta Emanuela, Panza Francesco
Department of Translational Biomedicine and Neuroscience "DiBraiN", University of Bari Aldo Moro, Bari, Italy.
Department of Interdisciplinary Medicine, "Cesare Frugoni" Internal and Geriatric Medicine and Memory Unit, University of Bari Aldo Moro, Bari, Italy.
Expert Opin Pharmacother. 2024 Apr;25(5):571-584. doi: 10.1080/14656566.2024.2345734. Epub 2024 Apr 27.
Tauopathies are a spectrum of clinicopathological neurodegenerative disorders with increased aggregates included in glia and/or neurons of hyperphosphorylated insoluble tau protein, a microtubule-associated protein. Progressive supranuclear palsy (PSP) is an atypical dopaminergic-resistant parkinsonian syndrome, considered as a primary tauopathy with possible alteration of tau isoform ratio, and tau accumulations characterized by 4 R tau species as the main neuropathological lesions.
In the present review article, we analyzed and discussed viable disease-modifying and some symptomatic pharmacological therapeutics for PSP syndrome (PSPS).
Pharmacological therapy for PSPS may interfere with the aggregation process or promote the clearance of abnormal tau aggregates. A variety of past and ongoing disease-modifying therapies targeting tau in PSPS included genetic, microtubule-stabilizing compounds, anti-phosphorylation, and acetylation agents, antiaggregant, protein removal, antioxidant neuronal and synaptic growth promotion therapies. New pharmacological gene-based approaches may open alternative prevention pathways for the deposition of abnormal tau in PSPS such as antisense oligonucleotide (ASO)-based drugs. Moreover, kinases and ubiquitin-proteasome systems could also be viable targets.
tau蛋白病是一系列临床病理神经退行性疾病,其特征是在神经胶质细胞和/或神经元中存在过度磷酸化的不溶性tau蛋白(一种微管相关蛋白)聚集体增加。进行性核上性麻痹(PSP)是一种非典型的多巴胺能抵抗性帕金森综合征,被认为是一种原发性tau蛋白病,可能存在tau异构体比例改变,且以4R tau蛋白亚型为主要神经病理损伤的tau蛋白聚集。
在本综述文章中,我们分析并讨论了针对PSP综合征(PSPS)的可行的疾病修饰治疗和一些对症药物治疗。
PSPS的药物治疗可能会干扰聚集过程或促进异常tau蛋白聚集体的清除。过去和正在进行的针对PSPS中tau蛋白的多种疾病修饰治疗包括基因治疗、微管稳定化合物、抗磷酸化和乙酰化剂、抗聚集剂、蛋白质清除、抗氧化剂、促进神经元和突触生长的治疗。新的基于药理学基因的方法可能为PSPS中异常tau蛋白的沉积开辟替代预防途径,例如基于反义寡核苷酸(ASO)的药物。此外,激酶和泛素-蛋白酶体系统也可能是可行的靶点。