Regulators of cholinergic signaling in disorders of the central nervous system

J Neurochem. 2021 Sep;158(6):1425-1438. doi: 10.1111/jnc.15332. Epub 2021 Mar 19.

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.

Keywords: Acetylcholine; inflammation; microRNA; neurology; transfer RNA fragments.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylcholine / genetics
  • Acetylcholine / metabolism*
  • Animals
  • Central Nervous System Diseases / drug therapy
  • Central Nervous System Diseases / genetics
  • Central Nervous System Diseases / metabolism*
  • Cholinergic Agents / pharmacology
  • Cholinergic Agents / therapeutic use*
  • Cholinergic Neurons / drug effects
  • Cholinergic Neurons / metabolism*
  • Cholinesterase Inhibitors / pharmacology
  • Cholinesterase Inhibitors / therapeutic use
  • Humans
  • RNA / genetics
  • RNA / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Cholinergic Agents
  • Cholinesterase Inhibitors
  • RNA
  • Acetylcholine