Understanding Abnormal c-JNK/p38MAPK Signaling in Amyotrophic Lateral Sclerosis: Potential Drug Targets and Influences on Neurological Disorders

Author(s): Rajeshwar Kumar Yadav, Elizabeth Minz, Sidharth Mehan*

Journal Name: CNS & Neurological Disorders - Drug Targets
Formerly Current Drug Targets - CNS & Neurological Disorders

Volume 20 , Issue 5 , 2021

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c-JNK (c-Jun N-terminal kinase) and p38 mitogen-activated protein kinase (MAPK) family members work in a cell-specific manner to regulate neuronal signals. The abnormal activation of these cellular signals can cause glutamate excitotoxicity, disrupted protein homeostasis, defective axonal transport, and synaptic dysfunction. Various pre-clinical and clinical findings indicate that the up-regulation of c-JNK and p38MAPK signaling is associated with neurological disorders. Exceptionally, a significant amount of experimental data has recently shown that dysregulated c-JNK and p38MAPK are implicated in the damage to the central nervous system, including amyotrophic lateral sclerosis. Furthermore, currently available information has shown that cJNK/p38MAPK signaling inhibitors may be a promising therapeutic alternative for improving histopathological, functional, and demyelination defects related to motor neuron disabilities. Understanding the abnormal activation of c-JNK/p38MAPK signaling and the prediction of motor neuron loss may help identify important therapeutic interventions that could prevent neurocomplications. Based on the involvement of c-JNK/p38MAPK signaling in the brain, we have assumed that the downregulation of the c-JNK/p38MAPK signaling pathway could trigger neuroprotection and neurotrophic effects towards clinicopathological presentations of ALS and other brain diseases. Thus, this research-based review also outlines the inhibition of c-JNK and p38MAPK signal downregulation in the pursuit of disease-modifying therapies for ALS.

Keywords: c-JNK, p38MAPK, amyotrophic lateral sclerosis, neuroinflammation, demyelination, motor neuron disease.

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Article Details

Year: 2021
Published on: 25 January, 2021
Page: [417 - 429]
Pages: 13
DOI: 10.2174/1871527320666210126113848
Price: $95

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