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.

College of Life Science Yangtze University Jingzhou China

Department of Chemistry Faculty of Science University of Hradec Kralove Hradec Kralove Czech Republic

MOE Joint International Research Laboratory of Animal Health and Food Safety College of Veterinary Medicine Nanjing Agricultural University Nanjing China

National Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues Huazhong Agricultural University Wuhan China

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HIF-1α is a "brake" in JNK-mediated activation of amyloid protein precursor and hyperphosphorylation of tau induced by T-2 toxin in BV2 cells

c-Jun N-terminal kinase signaling in cellular senescence

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer's Disease and Identifying Promising Drug Targets