Cholinergic and purinergic systems: A key to multiple sclerosis?

Multiple sclerosis (MS) commonly affects young adults and leads to a decreased quality of life due to different signs and symptoms that induce physical, cognitive, social, and psychological challenges. This disease, an autoimmune neurological disorder, is characterized by chronic inflammatory demyelination and axonal degeneration of the central nervous system (CNS). To date, its etiology is unknown. A large number of physiological functions are regulated by the cholinergic system because the acetylcholine (ACh) is released from cholinergic neurons and acts on other neurons, most of them not cholinergic in the brain, as well as in various nonneuronal cells, such as those of the immune system and blood; thus, it is considered an important modulatory pathway of both the central and peripheral nervous systems. Furthermore, the purinergic system has a significant role in neurotransmission as well as immune and inflammatory responses. Accumulating evidence has suggested the presence of a strong association between these systems and MS. Therefore, this review aims to present and discuss the main mechanisms that potentially explain the influence of the cholinergic and purinergic systems in multiple sclerosis. These mechanisms are discussed in light of available scientific evidence in humans and animal experimental models of MS. We hope that this review provides a better understanding of this subject, helping to guide future research and potential novel therapeutic strategies for patients with MS.