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image of Rapamycin and Autophagy: Potential Therapeutic Approach for Parkinson's Disease Treatment

Abstract

Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder marked by the degeneration of dopaminergic neurons in the substantia nigra, leading to characteristic motor symptoms such as bradykinesia, tremor, and rigidity, as well as a range of non-motor manifestations including cognitive impairment, mood disturbances and autonomic dysfunction. Among the multiple cellular mechanisms implicated in PD, the dysregulation of autophagy has gained significant attention in recent years. Autophagy is a crucial intracellular degradation pathway responsible for the removal of misfolded proteins and damaged organelles, processes that are particularly relevant in neurodegenerative diseases. Impairment of autophagic flux contributes to the accumulation of toxic protein aggregates and cellular stress in PD. Rapamycin, a compound originally isolated from , is a well-established inhibitor of the mechanistic target of rapamycin (mTOR), a central regulator of autophagy. Preclinical studies have shown that rapamycin can stimulate autophagic pathways by suppressing mTOR signalling, leading to increased expression of autophagy markers. These effects have been associated with reduced neuronal damage, improved motor performance and decreased accumulation of pathological proteins in PD models. This review provides an overview of current preclinical research on rapamycin’s neuroprotective potential in PD through autophagy enhancement. Although findings are promising, translating these outcomes into clinical practice necessitates a thorough understanding of rapamycin’s pharmacodynamics, optimal dosing strategies, potential side effects and long-term safety. Further research is essential to establish its therapeutic viability in human populations.

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2025-10-14
2025-11-25

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Rapamycin and Autophagy: Potential Therapeutic Approach for Parkinson's Disease Treatment
Bentham Science Publishers ; https://doi.org/10.2174/0118715273401017250918141227
/content/journals/cnsnddt/10.2174/0118715273401017250918141227
/content/journals/cnsnddt/10.2174/0118715273401017250918141227
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  • Article Type:     Review Article
Keywords: mTOR inhibitor ; Parkinson's disease ; Rapamycin ; ferroptosis ; mitophagy ; oxidative stress ; neuroprotection ; autophagy

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