神经退行性疾病的新分子靶点:治疗干预的新途径

IF 3.3 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Ezgi Eroglu, Nusin Harmanci
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引用次数: 0

摘要

阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症和额颞叶痴呆等神经退行性疾病是全球重大的健康负担,治疗选择有限。目前的治疗主要是对症治疗,不能改变疾病进展,强调迫切需要新的、基于机制的干预措施。分子神经科学的最新进展已经确定了几种非经典的致病途径,包括神经炎症、线粒体功能障碍、自噬和蛋白质平衡受损、突触变性和非编码RNA失调。在这篇重点综述中,我们重点介绍了新兴的分子靶点,如TREM2、NLRP3、mTOR、TFEB、PINK1和SIRT3,它们为治疗干预提供了有希望的途径。我们还讨论了在靶点验证和转化药物开发方面的挑战,同时提出了未来的研究方向,可能有助于设计更有效的治疗方法。更深入地了解这些分子机制对于开发对抗神经变性的疾病修饰策略至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Emerging Molecular Targets in Neurodegenerative Disorders: New Avenues for Therapeutic Intervention

Emerging Molecular Targets in Neurodegenerative Disorders: New Avenues for Therapeutic Intervention

Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and frontotemporal dementia represent a significant global health burden with limited therapeutic options. Current treatments are primarily symptomatic and fail to modify disease progression, emphasizing the urgent need for novel, mechanism-based interventions. Recent advances in molecular neuroscience have identified several non-classical pathogenic pathways, including neuroinflammation, mitochondrial dysfunction, impaired autophagy and proteostasis, synaptic degeneration and non-coding RNA dysregulation. In this focused review, we highlight emerging molecular targets such as TREM2, NLRP3, mTOR, TFEB, PINK1 and SIRT3, which offer promising avenues for therapeutic intervention. We also address challenges in target validation and translational drug development, while proposing future research directions that may facilitate the design of more effective treatments. A deeper understanding of these molecular mechanisms is essential for developing disease-modifying strategies to combat neurodegeneration.

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来源期刊
CiteScore
5.60
自引率
6.50%
发文量
126
审稿时长
1 months
期刊介绍: Basic & Clinical Pharmacology and Toxicology is an independent journal, publishing original scientific research in all fields of toxicology, basic and clinical pharmacology. This includes experimental animal pharmacology and toxicology and molecular (-genetic), biochemical and cellular pharmacology and toxicology. It also includes all aspects of clinical pharmacology: pharmacokinetics, pharmacodynamics, therapeutic drug monitoring, drug/drug interactions, pharmacogenetics/-genomics, pharmacoepidemiology, pharmacovigilance, pharmacoeconomics, randomized controlled clinical trials and rational pharmacotherapy. For all compounds used in the studies, the chemical constitution and composition should be known, also for natural compounds.
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