Abstract
One of the utmost frequently emerging neurodegenerative diseases, Parkinson’s disease (PD) must be comprehended through the forfeit of dopamine (DA)-generating nerve cells in the substantia nigra pars compacta (SN-PC). The etiology and pathogenesis underlying the emergence of PD is still obscure. However, expanding corroboration encourages the involvement of genetic and environmental factors in the etiology of PD. The destruction of numerous cellular components, namely oxidative stress, ubiquitin-proteasome system (UPS) dysfunction, autophagy-lysosome system dysfunction, neuroinflammation and programmed cell death, and mitochondrial dysfunction partake in the pathogenesis of PD. Present-day pharmacotherapy can alleviate the manifestations, but no therapy has been demonstrated to cease disease progression. Peroxisome proliferator-activated receptors (PPARs) are ligand-directed transcription factors pertaining to the class of nuclear hormone receptors (NHR), and are implicated in the modulation of mitochondrial operation, inflammation, wound healing, redox equilibrium, and metabolism of blood sugar and lipids. Numerous PPAR agonists have been recognized to safeguard nerve cells from oxidative destruction, inflammation, and programmed cell death in PD and other neurodegenerative diseases. Additionally, various investigations suggest that regular administration of PPAR-activating non-steroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, indomethacin), and leukotriene receptor antagonists (montelukast) were related to the de-escalated evolution of neurodegenerative diseases. The present review elucidates the emerging evidence enlightening the neuroprotective outcomes of PPAR agonists in in vivo and in vitro models experiencing PD. Existing articles up to the present were procured through PubMed, MEDLINE, etc., utilizing specific keywords spotlighted in this review. Furthermore, the authors aim to provide insight into the neuroprotective actions of PPAR agonists by outlining the pharmacological mechanism. As a conclusion, PPAR agonists exhibit neuroprotection through modulating the expression of a group of genes implicated in cellular survival pathways, and may be a propitious target in the therapy of incapacitating neurodegenerative diseases like PD.
Highlights
Parkinson’s disease (PD) is a common, intricate, progressive, multifaceted, and debilitating neurodegenerative disease, which is portrayed by the forfeiture of dopamine (DA) generating nerve cells in the substantia nigra pars compacta (SN-PC)
Afterwards, identical outcomes were observed in peripheral blood mononuclear cells (PBMCs) of patients suffering from PD, but no such effects were noticed in unaffected people [128]
Existing pharmacotherapy can palliate the manifestations associated with PD, but no therapy has been displayed to eradicate the disease evolution
Summary
Parkinson’s disease (PD) is a common, intricate, progressive, multifaceted, and debilitating neurodegenerative disease, which is portrayed by the forfeiture of dopamine (DA) generating nerve cells in the substantia nigra pars compacta (SN-PC). Three subtypes of PPARs have been promulgated, viz., PPAR-α, PPAR-β/δ, and PPAR-γ, and are pinpointed in various body regions These subtypes have been reported to partake in the modulation of inflammatory processes, and regulation of numerous incapacitating neurodegenerative conditions [8]. PPARs are activated with the aid of tiny lipophilic molecules, which subsequently form heterodimers with their partner named retinoid X receptors (RXR) in order to carry out comprehensive cytoplasmic stimulation. Several PPAR agonists, for instance, pioglitazone, rosiglitazone, fenofibrate, benzafibrate, and others have been shown to safeguard nerve cells from oxidative stress, inflammation, and programmed cell death in PD and other incapacitating neurodegenerative diseases and are enumerated in this review [10].
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