Regulators of cholinergic signaling in disorders of the central nervous system. Issue 6 (19th March 2021) - Winek, Katarzyna
Abstract: Cholinergic signaling is crucial in cognitive processes, and degenerating cholinergic projections are a pathological hallmark in dementia. Use of cholinesterase inhibitors is currently the main treatment option to alleviate symptoms of Alzheimer's disease and has been postulated as a therapeutic strategy in acute brain damage (stroke and traumatic brain injury). However, the benefits of this treatment are still not clear. Importantly, cholinergic receptors are expressed both by neurons and by astrocytes and microglia, and binding of acetylcholine to the α7 nicotinic receptor in glial cells results in anti‐inflammatory response. Similarly, the brain fine‐tunes the peripheral immune response over the cholinergic anti‐inflammatory axis. All of these processes are of importance for the outcome of acute and chronic neurological disease. Here, we summarize the main findings about the role of cholinergic signaling in brain disorders and provide insights into the complexity of molecular regulators of cholinergic responses, such as microRNAs and transfer RNA fragments, both of which may fine‐tune the orchestra of cholinergic mRNAs. The available data suggest that these small noncoding RNA regulators may include promising biomarkers for predicting disease course and assessing treatment responses and might also serve as drug targets to attenuate signaling cascades during overwhelming inflammation and to ameliorate regenerative capacities of neuroinflammation. Abstract : Acetylcholine (ACh) is one of the main neurotransmitters with versatile functions. Cholinergic signaling is crucial in cognitive processes and its disturbances are linked to neurodegenerative diseases. Importantly, not only neurons, but also glial cells respond to ACh over cholinergic receptors and ACh is used as signaling molecule by peripheral immune cells. In this review, we discuss the roles and importance of regulators of cholinergic signaling, including molecular fine‐tuners, in brain disease states focusing on chronic disorders (e.g. Alzheimer's and Parkinson's disease) and acute injury states (stroke, traumatic brain injury).