Affiliation:
1. Department of Pharmacology, Neuropharmacology Division, ISF College of Pharmacy, Moga, Punjab, India
Abstract
Multiple Sclerosis (MS) is a severe brain and spinal cord condition with a diverse autoimmune
response and a wide variety of demyelination symptoms that primarily affect young
adults. The primary reason for this disease is inflammation of white and grey matter caused by increased
production of proinflammatory cytokines, which further damages the progenitor oligodendrocytes
and appears to induce hypertrophy of the astrocytes and gliosis. Overexpression of the
JAK/STAT signaling pathway contributes directly to physiological and pathological results in motor
neuron diseases. Cytokines such as IL-17, IL-6, IL-12, TNF-α, and INF-ϒ use JAK/STAT signaling
to trigger self-reactive CD4+ T-cells and differentiate them into Th1 phenotypes that overactivate
immune reactions in the brain. Similarly, PPARγ plays a critical role in regulating the immune
response by providing an anti-inflammatory effect by inhibiting macrophage and cytokine
production activation. PPARγ also mediates the intrinsic molecular process of the T-cell, which selectively
regulates the differentiation of Th17. Various studies indicate the neuroprotective function
of PPARγ agonists by attenuating the JAK/STAT mediated activation of glial cells, inhibiting
interleukin, and the differentiation of Th1 cells. Therefore, to maintain the brain's immune system,
both PPARγ and JAK/STAT oppositely regulate each other. Dysregulation in JAK/STAT and
PPARγ signaling contributes to several physiological changes leading to neurological disorders, including
MS. Based on the above view, we have summarized the combined role of JAK/STAT-PPARγ
signaling in MS and explored potential therapeutic strategies for disease improvement by the
use of pathway modulators.
Publisher
Bentham Science Publishers Ltd.
Subject
General Health Professions
Cited by
20 articles.
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