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Review Article
- Drug Repositioning and Repurposing for Disease-Modifying Effects in Parkinson’s Disease
- Seong Ho Jeong, Phil Hyu Lee
- J Mov Disord. 2025;18(2):113-126. Published online February 7, 2025
- DOI: https://doi.org/10.14802/jmd.25008
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Abstract
PDF - Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder and is characterized by progressive dopaminergic and nondopaminergic neuronal loss and the presence of Lewy bodies, which are primarily composed of aggregated α-synuclein. Despite advancements in symptomatic therapies, such as dopamine replacement and deep brain stimulation, no disease-modifying therapies (DMTs) have been identified to slow or arrest neurodegeneration in patients with PD. Challenges in DMT development include disease heterogeneity, the absence of reliable biomarkers, and the multifaceted pathophysiology of PD, encompassing neuroinflammation, mitochondrial dysfunction, lysosomal impairment, and oxidative stress. Drug repositioning and repurposing strategies using existing drugs for new therapeutic applications offer promising approaches to accelerate the development of DMTs for PD. These strategies minimize time, cost, and risk by using compounds with established safety profiles. Prominent candidates include glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, ambroxol, calcium channel blockers, statins, iron-chelating agents, c-Abl inhibitors, and memantine. Although preclinical and early clinical studies have demonstrated encouraging results, numerous phase III trials have yielded unfavorable outcomes, elucidating the complexity of PD pathophysiology and the need for innovative trial designs. This review evaluates the potential of prioritized repurposed drugs for PD, focusing on their mechanisms, preclinical evidence, and clinical trial outcomes, and highlights the ongoing challenges and opportunities in this field.
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Citations
Citations to this article as recorded by
- Teneligliptin, a DPP4 inhibitor protects dopaminergic neurons in PD models via inhibiting of oxidative stress and ferroptosis
Linting Huang, Jiakai Pi, Liqin Gu, Zirou Liao, Wenya Wang
European Journal of Pharmacology.2025; 1002: 177782. CrossRef - Deciphering the Janus‐Faced Nature of the Apolipoprotein Superfamily in Parkinsonian Neurodegeneration: Molecular Crosstalk Between the Astroglial Secretome and Neuronal Homeostasis
Yingying Dai, Mingxia Bi, Qian Jiao, Xixun Du, Xi Chen, Chunling Yan, Hong Jiang
Movement Disorders.2025; 40(11): 2299. CrossRef - Glucagon-Like Peptide-1 Receptor Agonists Are Promising for the Treatment of Brain Diseases: an Outlook from the Perspective of Integrative Physiology
N. V. Gulyaeva
Journal of Evolutionary Biochemistry and Physiology.2025; 61(5): 1326. CrossRef - Therapeutic innovation through drug repurposing: A multidimensional approach toward treating Parkinson's disease
Saswati Swagatika Sahoo, Sudhir Kumar Paidesetty, Pratap Kumar Sahu, Swagata Pattanaik, Rambabu Dandela
Bioorganic Chemistry.2025; 166: 109129. CrossRef
- Teneligliptin, a DPP4 inhibitor protects dopaminergic neurons in PD models via inhibiting of oxidative stress and ferroptosis
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