Hypothesis: JNK signaling is a therapeutic target of neurodegenerative diseases
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem, přehledy
Odkazy
PubMed
34032377
DOI
10.1002/alz.12370
Knihovny.cz E-zdroje
- Klíčová slova
- Alzheimer's disease, JNK, amyloid beta, neurodegenerative diseases, tau,
- MeSH
- Alzheimerova nemoc genetika MeSH
- amyloidní beta-protein * metabolismus MeSH
- amyloidový prekurzorový protein beta * genetika metabolismus MeSH
- fosforylace MeSH
- genový targeting * MeSH
- JNK mitogenem aktivované proteinkinasy metabolismus MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- mozková kůra metabolismus patologie MeSH
- neurodegenerativní nemoci patologie MeSH
- neurony metabolismus MeSH
- Pan troglodytes MeSH
- prasata MeSH
- proteiny tau metabolismus MeSH
- signální transdukce * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- amyloidní beta-protein * MeSH
- amyloidový prekurzorový protein beta * MeSH
- JNK mitogenem aktivované proteinkinasy MeSH
- proteiny tau MeSH
The exact signaling leading to neurological dysfunction in neurodegenerative diseases is currently unknown. We hypothesize that the c-Jun N-terminal kinase (JNK) signaling pathway is a potential therapeutic target for neurodegenerative diseases. This postulate rests on extensive data from cell and animal experimental studies, demonstrating that JNK signaling plays a crucial role in the pathogenesis of neurodegenerative diseases. The sustained activation of JNK leads to synaptic dysfunction and even neuronal apoptosis, ultimately resulting in memory deficits and neurodegeneration. JNK phosphorylates the amyloid precursor protein and tau, ultimately resulting in the formation of extraneuronal senile plaques and intraneuronal neurofibrillary tangles. Our hypothesis could be validated by investigating the cerebral cortex of elderly chimpanzees injected with phosphorylated JNK or transgenic pig and chimpanzee models established using gene editing technology including CRISPR. This hypothesis provides clues for further understanding the molecular mechanisms of neurodegenerative diseases and the development of potential target therapeutic drugs.
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c-Jun N-terminal kinase signaling in cellular senescence