Neurodegenerative diseases associated with MAPK9 dysregulation.
| Neurodegenerative disease | Role of MAPK9 (JNK2) | Major pathological mechanisms | Key outcomes |
|---|---|---|---|
| Alzheimer’s disease (AD) | Increased MAPK9 activation in response to amyloid β accumulation and oxidative stress | Amyloid β toxicity, tau hyperphosphorylation, neuroinflammation, synaptic dysfunction | Cognitive decline, neuronal loss, memory impairment [51] |
| Parkinson’s disease (PD) | MAPK9-mediated apoptosis of dopaminergic neurons | α-Synuclein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation | Dopaminergic neuronal degeneration, motor dysfunction |
| Huntington’s disease (HD) | Activation by mutant huntingtin-induced cellular stress | Oxidative stress, mitochondrial impairment, apoptotic signalling | Striatal neuron degeneration, cognitive and motor deficits [66] |
| Ischemic brain injury | Rapid activation following cerebral ischemia and reperfusion | Excitotoxicity, oxidative stress, inflammatory cytokine release, apoptosis | Neuronal death and neurological impairment [67] |
| Vascular dementia | MAPK9 contributes to inflammation and ischemic neuronal damage | Chronic cerebral hypoperfusion, endothelial dysfunction, blood-brain barrier disruption, oxidative stress, neurovascular inflammation, and MAPK9-mediated apoptosis | Cognitive impairment and neuronal dysfunction [68] |
| Multiple sclerosis (MS) | MAPK9 participates in inflammatory and demyelinating processes | Immune cell activation, cytokine production, oxidative stress | Demyelination and neurodegeneration [69] |
| Frontotemporal dementia (FTD) | Dysregulated MAPK9 signalling is associated with protein aggregation and neuronal loss | Tau pathology, neuroinflammation, apoptotic signalling | Behavioural and cognitive dysfunction [70] |
MAPK9: mitogen-activated protein kinase 9; JNK2: c-Jun N-terminal kinase 2.
The authors would like to acknowledge the University of the Witwatersrand’s Research Office for awarding Dr. Otun a postdoctoral fellowship.
SO: Investigation, Writing—original draft. IA: Conceptualization, Supervision, Writing—review & editing. Both authors read and approved the submitted version.
The authors declare no conflicts of interest.
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Open access funding provided by the University of the Witwatersrand, and the authors would like to acknowledge the National Research Foundation (NRF) of South Africa for awarding Prof. Achilonu the CPRR research grant (Grant number CPRR23042899244). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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