ADMET and DMPK, Vol. 14 , 2026.
Review article
https://doi.org/10.5599/admet.3058
Neuroprotective cellular and molecular mechanisms of physical exercise on neurodegenerative diseases
Saswati Swagatika Sahoo
; School of Pharmaceutical Sciences, Siksha O Anusandhan University, Bhubaneswar, Odisha, India
Pratap Kumar Sahu
; School of Pharmaceutical Sciences, Siksha O Anusandhan University, Bhubaneswar, Odisha, India
Nishigandha Sa
; School of Pharmaceutical Sciences, Siksha O Anusandhan University, Bhubaneswar, Odisha, India
Anindita Behera
orcid.org/0000-0002-2990-0956
; Amity Institute of Pharmacy, Amity University, Kolkata, West Bengal, India
*
* Corresponding author.
Abstract
Background: Neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's disease are characterized by a progressive loss of neuronal function and loss of synaptic capacity. Physical exercise (PE) is one of the non-clinical techniques for the management of brain health and neurodegeneration. 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 (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.
Keywords
Physical exercise; neuroprotective; neurogenesis; neuronal survival; neuroendocrine regulation
Hrčak ID:
346787
URI
Publication date:
11.3.2026.
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