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Mechanisms: PE enhances the body's metabolic functions through cellular and molecular changes. It trades off metabolic functions, energy expenditure, and signalling processes to ensure physiological homeostasis and defence against disease. Exercise produces cascades, at the molecular level, including neurotrophic signalling, similar to those generated by drugs. It increases the levels of the brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor\u00a0(VEGF). These elements favour the growth of new neurons, vascular enlargement, and synaptic plasticity. PE also induces microglial cells to attain a neuroprotective, anti-inflammatory phenotype, reduces detrimental cytokines, promotes cellular clearance through autophagy, restores neurotransmitter homogenisation, and induces hippocampal cell formation. Collectively, it acts as a powerful modulator of health and brain activity. Implications: The aggregate processes enhance neuronal vulnerability to harm, aid cognitive functioning, and ensure the stability of neural networks. Conclusion: PE is an exciting additive therapy for preventing and treating various neurodegenerative disorders by orchestrating a diverse array of cellular and molecular responses.<\/jats:p>","DOI":"10.5599\/admet.3058","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T11:18:08Z","timestamp":1773227888000},"source":"Crossref","is-referenced-by-count":1,"title":["Neuroprotective cellular and molecular mechanisms of physical exercise on neurodegenerative diseases"],"prefix":"10.5599","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7790-7923","authenticated-orcid":false,"given":"Saswati Swagatika","family":"Sahoo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8805-8682","authenticated-orcid":false,"given":"Pratap Kumar","family":"Sahu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9259-7252","authenticated-orcid":false,"given":"Nishigandha","family":"Sa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2990-0956","authenticated-orcid":false,"given":"Anindita","family":"Behera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3564","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"key":"167583","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23063245"},{"key":"167584","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-022-01272-x"},{"key":"167585","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-025-02751-9"},{"key":"167586","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2023.05.007"},{"key":"167587","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241310809"},{"key":"167588","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2025.1579208"},{"key":"167589","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-025-02886-9"},{"key":"167590","doi-asserted-by":"publisher","DOI":"10.3390\/biom14101241"},{"key":"167591","doi-asserted-by":"publisher","DOI":"10.1186\/s40798-015-0016-x"},{"key":"167592","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00188"},{"key":"167593","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21165895"},{"key":"167594","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2020.110842"},{"key":"167595","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-017-0576-y"},{"key":"167596","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1444716"},{"key":"167597","doi-asserted-by":"publisher","DOI":"10.3390\/cells8070691"},{"key":"167598","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1403-x"},{"key":"167599","doi-asserted-by":"publisher","DOI":"10.4172\/2329-6887.1000125"},{"key":"167600","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00565.2022"},{"key":"167601","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2024.1338875"},{"key":"167602","doi-asserted-by":"publisher","DOI":"10.32604\/biocell.2024.048776"},{"key":"167603","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2015.06.016"},{"key":"167604","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252312924"},{"key":"167605","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-025-01208-3"},{"key":"167606","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2024.115218"},{"key":"167607","doi-asserted-by":"publisher","DOI":"10.1007\/s11332-022-01030-y"},{"key":"167608","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000003030"},{"key":"167609","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)00184-9"},{"key":"167610","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160869"},{"key":"167611","doi-asserted-by":"publisher","DOI":"10.1097\/PSY.0b013e3181d14633"},{"key":"167612","doi-asserted-by":"publisher","DOI":"10.1080\/13607863.2019.1584785"},{"key":"167613","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23115938"},{"key":"167614","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-96-6202-9_2"},{"key":"167615","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2025.102698"},{"key":"167616","doi-asserted-by":"publisher","DOI":"10.1111\/psyg.13207"},{"key":"167617","doi-asserted-by":"publisher","DOI":"10.1590\/0004-282x-anp-2020-0539"},{"key":"167618","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.03.018"},{"key":"167619","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180958"},{"key":"167620","unstructured":"[38] Z. 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