Understanding Abnormal c-JNK/p38MAPK Signaling Overactivation Involved in the Progression of Multiple Sclerosis: Possible Therapeutic Targets and Impact on Neurodegenerative Diseases.

Demyelination, immune dysregulation, and neuroinflammation are the most common triggers of motor neuron disorders such as multiple sclerosis (MS). MS is a chronic demyelinating neurodegenerative disease of the central nervous system caused by abnormal immune activation, which causes myelin sheath damage. Cell signal transduction pathways are required for a variety of physiological and pathological processes in the brain. When these signaling systems become overactive, they can lead to disease progression. In various physiological conditions, abnormal mitogen-activated protein kinase (MAPK) activation is associated with several physiological dysfunctions that cause neurodegeneration. Previous research indicates that c-JNK and p38MAPK signaling play critical roles in neuronal growth and differentiation. c-JNK/p38MAPK is a member of the MAPK family, which regulates metabolic pathways, cell proliferation, differentiation, and apoptosis that control certain neurological activities. During brain injuries, c-JNK/p38MAPK also affects neuronal elastic properties, nerve growth, and cognitive processing. This review systematically linked abnormal c-JNK/p38MAPK signaling activation to multiple neuropathological pathways in MS and related neurological dysfunctions. MS progression is linked to genetic defects, oligodendrocyte destruction, glial overactivation, and immune dysregulation. We concluded that inhibiting both the c-JNK/p38MAPK signaling pathways can promote neuroprotection and neurotrophic effects against the clinical-pathological presentation of MS and influence other neurological disorders. As a result, the potential benefits of c-JNK/p38MAPK downregulation for the development of disease-modifying treatment interventions in the future could include MS prevention and related neurocomplications.