Title:Understanding Abnormal c-JNK/p38MAPK Signaling in Amyotrophic Lateral Sclerosis: Potential Drug Targets and Influences on Neurological Disorders
Volume: 20
Issue: 5
Author(s): Rajeshwar Kumar Yadav, Elizabeth Minz and Sidharth Mehan*
Affiliation:
- Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab,India
Keywords:
c-JNK, p38MAPK, amyotrophic lateral sclerosis, neuroinflammation, demyelination, motor neuron disease.
Abstract: 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 c-
JNK/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.
