Abstract
Multiple sclerosis (MS) is a neurodegenerative disease with a complex autoimmune component, and it has a high prevalence among middle-aged females. The manifestations of the disease range from episodic somatosensory dysfunction to progressive and permanent central nervous system (CNS) damage. Due to a high prevalence of psychiatric comorbidities and proven abnormalities in serotonin (5-HT) levels among MS patients, they are usually on drugs that modify the serotonergic system. Through a comprehensive literature review of studies published in the last 10 years related to 5-HT in MS and its therapeutic applications, we aimed to elucidate the mechanism behind the neurotransmitter (NT) levels’ abnormalities. Most importantly, we endeavored to gather the most up-to-date information about the full therapeutic potential of agents acting on this system. We discovered that multiple processes cause low levels of 5-HT in MS patients. The varying levels of the availability of the 5-HT transporter (SERT) in the CNS decreasing overall tryptophan (TRP) levels, and diversion of the amino acid away from its synthetic pathway constitute some of those. Studies in animals have shown that 5-HT levels’ elevations could cause immune-modulating effects and could probably slow down the disease progression rate. Human studies have shown a more diverse and complex response. Promising results have been obtained in the last 10 years regarding 5-HT’s immune-modulatory role in MS patients and its therapeutic applications. Human studies with a larger population and feasible designs are still needed to fully ascertain the effects of serotonin on the immune system and disease progression in patients with MS.
Highlights
BackgroundIt is estimated that there are more than two million people suffering from multiple sclerosis (MS) globally [1]
Multiple sclerosis (MS) is a neurodegenerative disease with a complex autoimmune component, and it has a high prevalence among middle-aged females
We discovered that multiple processes cause low levels of 5-HT in MS patients
Summary
It is estimated that there are more than two million people suffering from multiple sclerosis (MS) globally [1]. Elevated activity of the KP has been reported in patients with MS, especially in those with the relapsing-remitting subtype [2], driving TRP into its catabolic pathway and away from the synthesis of the NT This diversion is accomplished primarily through the induction of the enzyme IDO by cytokines like interferon-gamma (IFNγ), interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-α) released in high titers in the inflammatory foci [14]. A randomized controlled trial (RCT) in 2019 showed an increase in 5-HT levels with aerobic exercise, and it associated this phenomenon with the improvement in the participants' sleep quality [23] Both studies had a small sample size, the results are promising for future therapies on targeting the serotonergic system to improve the overall health of MS patients and their quality of life.
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