A Research Update on Exendin-4 as a Novel Molecule Against
Parkinson’s Disease

Niraj   Kumar   Singh; Ashini      Singh; Mini      Varshney; Ritik      Agrawal
doi:10.2174/1566524023666230529093314
Abstract

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, and its consequences severely influence the quality of a patient’s life and mobility. PD is characterized by bradykinesias with tremors and/or rigidity. Pathophysiologically, PD is associated with the gradual degeneration of dopaminergic neurons in the substantia nigra pars compacta of the midbrain, neuroinflammation, increased accumulation of the alpha (α)-synuclein, overburden of oxidative stress, and mitochondrial dysfunction. To date, there are no effective therapies with underlying shreds of evidence that alters the progression of PD. Exendin-4, a glucagon-like peptide 1 (GLP-1) receptor agonist, has gained attention for its tremendous neuroprotective potential against numerous neurodegenerative disorders, including PD. Further, several pieces of research evidence have suggested the beneficial role of Exendin-4 in PD-like experimental models. The present review article highlights the preclinical and clinical evidence of the therapeutic benefits of Exendin-4 against PD. Exendin-4 reverses the PD-like symptoms in experimental animals by dramatically minimizing the loss of dopaminergic neuronal and accumulation of α-synuclein in the PD-like brain. Further, it also reduces the mitochondrial toxicity and expression of pro-inflammatory mediators such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β. These observations designate that Exendin-4 is a multifactorial compound that could be considered a safe, effective, and new ingredient for developing clinically useful pharmacotherapy for managing PD-like manifestations.
Keywords: Exendin-4, Parkinson's disease, α-Synuclein, GLP-1 analogue, mitochondria, neuroprotection.
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DOI https://dx.doi.org/10.2174/1566524023666230529093314	Print ISSN 1566-5240
Publisher Name Bentham Science Publisher	Online ISSN 1875-5666
Current Molecular Medicine

A Research Update on Exendin-4 as a Novel Molecule Against Parkinson’s Disease

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