Physical exercise modulates the expression of non-coding RNAs linked to neuroplasticity, inflammation, oxidative stress, mitochondrial function, and neuronal survival, according to a review published in Cellular and Molecular Neurobiology. Authors TianLai Zhao and Bihua Chen synthesized accumulating preclinical and clinical evidence to evaluate how these regulatory molecules respond to physical activity across aging contexts and multiple neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis.
Non-coding RNAs, encompassing microRNAs, long non-coding RNAs, and circular RNAs, have emerged as promising molecular biomarkers due to their regulatory roles in gene expression. In addition to their functional involvement in cellular pathways, these molecules display remarkable stability within circulating biological fluids. The review notes that exercise-responsive non-coding RNAs are detectable in blood, cerebrospinal fluid, and extracellular vesicles, underscoring their viability as accessible, non-invasive indicators.
The identification of reliable biomarkers addresses major ongoing clinical challenges in managing neurodegenerative diseases, which are characterized by progressive neuronal degeneration, cognitive decline, and limited therapeutic options. Because timely diagnosis and effective monitoring remain difficult, tracking circulating exercise-modulated molecules offers significant potential for disease diagnosis, prognosis, and therapeutic monitoring. Zhao and Chen emphasize that these exercise-responsive signatures could aid in early detection and personalized intervention strategies.
To evaluate these molecular dynamics, the authors adopted a framework that implemented a reproducible literature search strategy and applied a comparative analysis across multiple disease states. This approach integrates mechanistic and translational perspectives to distinguish disease-specific and exercise-specific non-coding RNA signatures rather than relying solely on descriptive findings. Furthermore, the synthesis discusses emerging methodologies, including liquid biopsy and multi-omics integration, to overcome current research gaps and enhance the translational utility of non-coding RNA biomarkers in neurodegenerative disorders.
Subject of Research: Exercise-responsive non-coding RNAs in neurodegeneration and aging
Article Title: Exercise-Responsive Non-coding RNAs in Neurodegeneration and Aging: Molecular Mechanisms, Systemic Adaptations, and Biomarker Potential
Article References: Zhao, T., & Chen, B. (2026). Exercise-Responsive Non-coding RNAs in Neurodegeneration and Aging: Molecular Mechanisms, Systemic Adaptations, and Biomarker Potential. Cellular and Molecular Neurobiology. https://doi.org/10.1007/s10571-026-01850-3
Image Credits: AI Generated
DOI: 10.1007/s10571-026-01850-3
Keywords: non-coding RNA, neurodegenerative diseases, physical exercise, biomarkers, microRNA, aging, cellular neurobiology, liquid biopsy, Exercise-Responsive, Non-coding, RNAs, Neurodegeneration
