Toader Corneliu, Tataru Calin Petru, Munteanu Octavian, Serban Matei, Covache-Busuioc Razvan-Adrian, Ciurea Alexandru Vlad, Enyedi Mihaly
Department of Neurosurgery, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.
Department of Vascular Neurosurgery, National Institute of Neurology and Neurovascular Diseases, 077160 Bucharest, Romania.
Int J Mol Sci. 2024 Nov 24;25(23):12613. doi: 10.3390/ijms252312613.
Neurodegenerative diseases, such as Alzheimer's, Parkinson's, ALS, and Huntington's, remain formidable challenges in medicine, with their relentless progression and limited therapeutic options. These diseases arise from a web of molecular disturbances-misfolded proteins, chronic neuroinflammation, mitochondrial dysfunction, and genetic mutations-that slowly dismantle neuronal integrity. Yet, recent scientific breakthroughs are opening new paths to intervene in these once-intractable conditions. This review synthesizes the latest insights into the underlying molecular dynamics of neurodegeneration, revealing how intertwined pathways drive the course of these diseases. With an eye on the most promising advances, we explore innovative therapies emerging from cutting-edge research: nanotechnology-based drug delivery systems capable of navigating the blood-brain barrier, gene-editing tools like CRISPR designed to correct harmful genetic variants, and stem cell strategies that not only replace lost neurons but foster neuroprotective environments. Pharmacogenomics is reshaping treatment personalization, enabling tailored therapies that align with individual genetic profiles, while molecular diagnostics and biomarkers are ushering in an era of early, precise disease detection. Furthermore, novel perspectives on the gut-brain axis are sparking interest as mounting evidence suggests that microbiome modulation may play a role in reducing neuroinflammatory responses linked to neurodegenerative progression. Taken together, these advances signal a shift toward a comprehensive, personalized approach that could transform neurodegenerative care. By integrating molecular insights and innovative therapeutic techniques, this review offers a forward-looking perspective on a future where treatments aim not just to manage symptoms but to fundamentally alter disease progression, presenting renewed hope for improved patient outcomes.
神经退行性疾病,如阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和亨廷顿病,仍然是医学上的巨大挑战,它们进展无情且治疗选择有限。这些疾病源于一系列分子紊乱——蛋白质错误折叠、慢性神经炎症、线粒体功能障碍和基因突变——这些紊乱会慢慢破坏神经元的完整性。然而,最近的科学突破正在为干预这些曾经难以治疗的疾病开辟新途径。这篇综述综合了对神经退行性变潜在分子动力学的最新见解,揭示了相互交织的通路如何驱动这些疾病的发展进程。着眼于最有前景的进展,我们探索了前沿研究中出现的创新疗法:能够穿越血脑屏障的基于纳米技术的药物递送系统、旨在纠正有害基因变异的如CRISPR这样的基因编辑工具,以及不仅能替代受损神经元还能营造神经保护环境的干细胞策略。药物基因组学正在重塑治疗的个性化,使定制疗法能够与个体基因特征相匹配,而分子诊断和生物标志物正在开启一个早期、精确疾病检测的时代。此外,随着越来越多的证据表明微生物群调节可能在减少与神经退行性进展相关的神经炎症反应中发挥作用,关于肠脑轴的新观点引发了人们的兴趣。综上所述,这些进展标志着向一种全面、个性化方法的转变,这种方法可能会改变神经退行性疾病的治疗方式。通过整合分子见解和创新治疗技术,这篇综述对未来提供了一个前瞻性的视角,在未来,治疗不仅旨在控制症状,而且要从根本上改变疾病进展,为改善患者预后带来新的希望。
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