精确酶:神经退行性疾病的靶向药物发现。

IF 1.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Sampriti Paul, Prashant Tiwari, Sonal Dubey
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引用次数: 0

摘要

神经退行性疾病,如阿尔茨海默病、帕金森病和ALS,以进行性神经元功能障碍为特征,治疗选择有限。分子生物学和药物开发的最新进展突出了精确酶靶向的治疗前景,为疾病调节和症状管理提供了新的策略。方法:使用PubMed、Scopus和ScienceDirect进行了近期/当前的综合文献综述。包括基于酶的靶点、高通量筛选和神经变性分子对接的研究。采用主题合成法根据酶类、疾病相关性和治疗结果对结果进行分类。结果:激酶、蛋白酶和氧化还原酶等关键酶家族被确定为疾病进展的关键调节因子。新出现的酶靶向化合物显示出增强的生物利用度、血脑屏障通透性和疾病特异性功效。新的筛选平台和计算模型使抑制剂的精确选择,显着提高治疗指数和减少脱靶效应。讨论:靶向与神经炎症、氧化应激和蛋白质错误折叠有关的酶已显示出改善疾病的潜力。整合精准药物发现工具,如人工智能辅助建模和酶动力学,支持合理的药物设计。然而,由于酶表达的可变性和疾病异质性,翻译挑战仍然存在。结论:未来的研究应侧重于改进酶抑制剂和整合生物标志物,以促进神经退行性疾病的个性化治疗策略。随着对酶在神经变性中的作用的理解加深,精确酶靶向药物的发现在改变神经治疗方法方面具有重要的前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Precision Enzyme: Targeted Drug Discovery in Neurodegenerative Disorders.

Introduction: Neurodegenerative disorders such as Alzheimer's, Parkinson's, and ALS are characterized by progressive neuronal dysfunction with limited therapeutic options. Recent advances in molecular biology and drug development have highlighted the therapeutic promise of precision enzyme targeting, offering novel strategies for disease modulation and symptom management.

Methods: A comprehensive literature review spanning recent/current was conducted using PubMed, Scopus, and ScienceDirect. Studies focusing on enzyme-based targets, high-throughput screening, and molecular docking in neurodegeneration were included. Thematic synthesis was employed to categorize findings based on enzyme class, disease relevance, and therapeutic outcomes.

Results: Key enzyme families such as kinases, proteases, and oxidoreductases were identified as pivotal modulators in disease progression. Emerging enzyme-targeted compounds demonstrated enhanced bioavailability, blood-brain barrier permeability, and disease-specific efficacy. Novel screening platforms and computational modeling enabled the precise selection of inhibitors, significantly improving the therapeutic index and reducing off-target effects.

Discussion: Targeting enzymes implicated in neuroinflammation, oxidative stress, and protein misfolding has shown disease-modifying potential. Integrating precision drug discovery tools, such as AI-assisted modeling and enzyme kinetics, supports rational drug design. However, translational challenges persist due to variability in enzyme expression and disease heterogeneity.

Conclusion: Future research should focus on refining enzyme inhibitors and integrating biomarkers to facilitate personalized treatment strategies for neurodegenerative disorders. As the understanding of enzymatic roles in neurodegeneration deepens, precision enzyme-targeted drug discovery holds significant promise in transforming neurotherapeutic approaches.

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来源期刊
Protein and Peptide Letters
Protein and Peptide Letters 生物-生化与分子生物学
CiteScore
2.90
自引率
0.00%
发文量
98
审稿时长
2 months
期刊介绍: Protein & Peptide Letters publishes letters, original research papers, mini-reviews and guest edited issues in all important aspects of protein and peptide research, including structural studies, advances in recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, and drug design. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallization and preliminary structure determination of biologically important proteins are considered only if they include significant new approaches or deal with proteins of immediate importance, and preliminary structure determinations of biologically important proteins. Purely theoretical/review papers should provide new insight into the principles of protein/peptide structure and function. Manuscripts describing computational work should include some experimental data to provide confirmation of the results of calculations. Protein & Peptide Letters focuses on: Structure Studies Advances in Recombinant Expression Drug Design Chemical Synthesis Function Pharmacology Enzymology Conformational Analysis Immunology Biotechnology Protein Engineering Protein Folding Sequencing Molecular Recognition Purification and Analysis
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