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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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http://dx.doi.org/10.2174/0109298665391103250825102319 | DOI Listing |
Mol Divers
September 2025
Department of Biotechnology, National Institute of Technology Raipur, Raipur, Chhattisgarh, 492001, India.
Traditional drug discovery methods like high-throughput screening and molecular docking are slow and costly. This study introduces a machine learning framework to predict bioactivity (pIC₅₀) and identify key molecular properties and structural features for targeting Trypanothione reductase (TR), Protein kinase C theta (PKC-θ), and Cannabinoid receptor 1 (CB1) using data from the ChEMBL database. Molecular fingerprints, generated via PaDEL-Descriptor and RDKit, encoded structural features as binary vectors.
View Article and Find Full Text PDFMol Divers
September 2025
State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, Xinjiang, China.
Aurora kinases are a group of serine/threonine kinases essential for cell mitosis, comprising Aurora A, B, and C. However, the Aurora B is overexpressed in multiple tumors and the aurone has been proved to exhibit potent inhibitory activity against Aurora B kinase by our group. The indolinone was considered as an aurone scaffold hopping analog, and the indolinone-based Aurora B inhibitor library (3577 molecules) was constructed by FBDD strategy.
View Article and Find Full Text PDFMol Divers
September 2025
Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University, Nanjing, 211198, China.
Drug absorption significantly influences pharmacokinetics. Accurately predicting human oral bioavailability (HOB) is essential for optimizing drug candidates and improving clinical success rates. The traditional method based on experiment is a common way to obtain HOB, but the experimental method is time-consuming and costly.
View Article and Find Full Text PDFMol Biol Rep
September 2025
School of Pharmacy, Heilongjiang University of Chinese Medicine, NO 24 Heping Road, 150040, Harbin, P. R. China.
Lysosome-dependent cell death (LDCD) is a regulated form of cell death initiated by increased lysosomal membrane permeability, leading to the cytoplasmic release of lysosomal enzymes and subsequent cellular damage. Molecular mechanisms controlling LDCD include lysosomal membrane instability and lysosomal enzyme release, which together lead to cell damage. A more profound comprehension of these underlying mechanisms may reveal new therapeutic targets for diseases associated with lysosomal dysfunction.
View Article and Find Full Text PDFNanoscale
September 2025
Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, The School of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350122, People's Republic of China.
The rational design of non-precious metal catalysts as a replacement for Pd is of great importance for catalyzing various important chemical reactions. To realize this purpose, the palladium-like superatom NbN was doped into a defective graphene quantum dot (GQD) model with a double-vacancy site to design a novel single superatom catalyst, namely, NbN@GQD, based on density functional theory (DFT), and its catalytic activity for the Suzuki reaction was theoretically investigated. Our results reveal that this designed catalyst exhibits satisfactory activity with a small rate-limiting energy barrier of 25.
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