Academic Journal
Molecular crosstalk between MAPK signaling and neuroprotective pathways in Parkinson's disease: from pathogenesis to therapeutic potential.
| Τίτλος: | Molecular crosstalk between MAPK signaling and neuroprotective pathways in Parkinson's disease: from pathogenesis to therapeutic potential. |
|---|---|
| Συγγραφείς: | Shalabi MG; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakala 72388, Saudi Arabia. Electronic address: mgshalbi@ju.edu.sa., Al-Kuraishy HM; Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq. Electronic address: haydermutter@uomustansiriyah.edu.iq., Shokr MM; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sinai University- Arish Branch, Arish 45511, Egypt. Electronic address: mostafa.mohsen@su.edu.eg., Batiha GE; Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, AlBeheira, Egypt. Electronic address: Gaberelsaberbatiha@gmail.com. |
| Πηγή: | Neuroscience [Neuroscience] 2026 Aug 28; Vol. 610, pp. 297-310. Date of Electronic Publication: 2026 Jun 19. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 7605074 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-7544 (Electronic) Linking ISSN: 03064522 NLM ISO Abbreviation: Neuroscience Subsets: MEDLINE |
| Imprint Name(s): | Publication: [New York?] : Elsevier Science Original Publication: Oxford, Elmsford, N. Y., Pergamon Press |
| Ιατρικοί όροι (MeSH): | Parkinson Disease*/metabolism , Parkinson Disease*/drug therapy , MAP Kinase Signaling System*/physiology , MAP Kinase Signaling System*/drug effects , Neuroprotection*/physiology , Mitogen-Activated Protein Kinases*/metabolism, Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Dopaminergic Neurons/metabolism ; Humans ; Animals |
| Περίληψη: | Mitogen-activated protein kinase (MAPK) signaling is increasingly recognized as a central regulator in the pathogenesis of Parkinson's disease (PD). PD is a chronic neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), driven by a complex interplay of mitochondrial dysfunction, oxidative stress, and neuroinflammation. While basal MAPK activity is essential for neuroprotection and neuronal growth, its overactivation, specifically via the JNK and p38 cascades, accelerates neurodegeneration. This review explores the molecular landscape of MAPK signaling, detailing how its dysregulation promotes the accumulation of alpha-synuclein and the activation of microglia. Furthermore, it highlights critical crosstalk between MAPK and other vital pathways, including the inhibition of the neuroprotective PI3K/AKT and PP2A pathways and the detrimental activation of GSK-3β and PTEN signaling. Preclinical evidence strongly supports the use of MAPK inhibitors to mitigate dopaminergic neurotoxicity and reduce proinflammatory cytokine release. Despite promising results in experimental models and the development of highly selective inhibitors, clinical translation remains challenging due to potential systemic toxicities. This manuscript provides a comprehensive synthesis of mounting and mooting evidence, positioning MAPK inhibition as a potent, albeit complex, adjuvant strategy for delaying the onset and progression of PD neuropathology. (Copyright © 2026 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: MAPK signaling; PI3K/AKT/GSK-3β pathway; Parkinson’s disease; neurodegenerative disease; α-synuclein |
| Substance Nomenclature: | 0 (Neuroprotective Agents) EC 2.7.11.24 (Mitogen-Activated Protein Kinases) |
| Entry Date(s): | Date Created: 20260619 Date Completed: 20260716 Latest Revision: 20260716 |
| Update Code: | 20260717 |
| DOI: | 10.1016/j.neuroscience.2026.06.026 |
| PMID: | 42320726 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1873-7544 |
|---|---|
| DOI: | 10.1016/j.neuroscience.2026.06.026 |