The cholinergic anti-inflammatory pathway: An innovative treatment strategy for neurological diseases

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Graphical abstractHighlightsNeuronal or non-neuronal acetylcholine plays a crucial role in inflammatory diseases.The complete cholinergic system exists in peripheral and central immune cells.The cholinergic anti-inflammatory pathway (CAIP) participates in regulating inflammation.Vagus nerve stimulation effectively relieves neuroinflammation.The CAIP may act as an alternative method to improve neurological inflammatory diseases.Acetylcholine (ACh), as a classical neurotransmitter, regulates the neuronal network in response to internal and external stimuli. In recent decades, the biology of ACh has been endowed with unparalleled new insights, especially with respect to cholinergic anti-inflammatory properties in non-neuronal cells. In fact, a mechanism frequently referred to as the “cholinergic anti-inflammatory pathway” has been termed to describe interactions between the central nervous system (CNS) and the immune system via vagus nerve. As well documented, immune cells express choline acetyltransferase, a direct synthetase for ACh, and other corresponding cholinergic components. Alternatively, the ACh released from immune cells or cholinergic neurons modulates immune function in an autocrine/paracrine manner by acting on its receptors. Moreover, muscarinic or nicotinic ACh receptors on various immune cells and CNS glial cells administer the work of their respective agonists, causing functional and biochemical changes. In this review, we focus on the anti-inflammatory benefits of non-neuronal and neuronal ACh as a means of providing new insights into treating inflammation-related neurological diseases, as exemplified by those described herein.

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