Gamma-amino butyric acid (GABA) is a major inhibitory neurotransmitter found in several regions of the brain and known to have various significant physiological roles as a potent bioactive compound. Malfunction of GABAergic neuronal signaling prompts to cause severe psychiatric symptoms in numerous mental disorders. Several drugs are available in clinical practice for neuropsychiatric disorders targeting through GABAergic pathway, with notable adverse effects. Interestingly, in recent years, researchers are focusing on natural compounds altering GABAergic neurotransmission for various psychiatric disorders due to its wide range of therapeutic efficacy and safety. The enormous variety of natural compounds, namely alkaloids, flavonoids, terpenoids, polyacetylenic alcohols, alkanes and fatty acids were reported to alter the GABAergic transmission through its receptors and or by influencing the transmission, synthesis and metabolism of GABA. Natural compounds are able to cross the blood brain barrier and influence the GABA functions in order to treat anxiety, mania, schizophrenia and cognitive disorders. Therefore, this current chapter describes on natural products which have the potential to alter the GABAergic neurotransmission and its therapeutical benefits in treating several neuropsychiatry disorders using various pharmacological methods.
Multiple sclerosis (MS) is a neurological condition with a complicated autoimmune component that mainly affects women in their forties and fifties. The disorder appears in several forms, ranging from episodic somatosensory impairment to progressive and irreversible central nervous system (CNS) injury. The fundamental cause of this disorder is lack of serotonin (5HT), a neurotransmitter with numerous immune effects. Decreased 5-HT levels or synthesis have also been related to increased proinflammatory cytokines in the CNS. Among several other proinflammatory cytokines, two prototypic pro-inflammatory cytokines, interleukin-1 (IL-1β) and tumor necrosis factor (TNF-α) have been identified as primary effectors of neuroinflammation's functional effects on neurodegeneration.TNF-α is a pleiotropic cytokine that regulates homeostasis, immunity, and inflammation and IL-1β is also a cytokine with neuroimmunological and neurophysiological functions. MS patients are usually on drugs that change the serotonergic system, because of increased clinical comorbidities and proven serotonin deficits. Several studies have shown that higher 5-HT levels have anti-inflammatory and immune-modulating properties, which could help to delay the progression of the disease.
Multiple sclerosis (MS) is one of the most affecting autoimmune neurodegenerative disease characterized by chronic neuroinflammation, demyelination and impaired neuronal conduction. The oligodendrocytes toxicity by inflammatory cytokines and oxy-radicals are considered to be the most important factor in demyelination of motor neurons. The dysfunction of neuronal A1 adenosine receptor (A1AR) contributes to the demyelination of neurons by triggering the pro-inflammatory cytokines, oxy-radicals and neuroinflammatory cascades. In MS pathogenesis, Antigen presenting cells, MHC protein, CD4+T-cells, GM-CSF along with effector cells enhance the activation of macrophages in adenosinergic declined conditions, where it shows cumulative effects which leads to oligodendrocytes toxicity and demyelination of motor neurons. In general, A1AR is mainly expressed in macrophage lineage cells in central nervous system which could control the macrophage activation upon stimulation by its agonists. In this review, we have mainly emphasized on the pathogenesis of MS and highlighted the importance of adenosinergic system in reversing the molecular events in MS. In addition, we have discussed about the beneficial role of A1AR agonists in MS management.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.