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Review
. 2022 Mar 10;27(6):1816.
doi: 10.3390/molecules27061816.

Role of Cholinergic Signaling in Alzheimer's Disease

Zhi-Ru Chen  1   2 , Jia-Bao Huang  1   2 , Shu-Long Yang  3   4 , Fen-Fang Hong  1
Affiliations
Review

Role of Cholinergic Signaling in Alzheimer's Disease

Zhi-Ru Chen et al. Molecules. .

Abstract

Acetylcholine, a neurotransmitter secreted by cholinergic neurons, is involved in signal transduction related to memory and learning ability. Alzheimer's disease (AD), a progressive and commonly diagnosed neurodegenerative disease, is characterized by memory and cognitive decline and behavioral disorders. The pathogenesis of AD is complex and remains unclear, being affected by various factors. The cholinergic hypothesis is the earliest theory about the pathogenesis of AD. Cholinergic atrophy and cognitive decline are accelerated in age-related neurodegenerative diseases such as AD. In addition, abnormal central cholinergic changes can also induce abnormal phosphorylation of ttau protein, nerve cell inflammation, cell apoptosis, and other pathological phenomena, but the exact mechanism of action is still unclear. Due to the complex and unclear pathogenesis, effective methods to prevent and treat AD are unavailable, and research to explore novel therapeutic drugs is various and active in the world. This review summaries the role of cholinergic signaling and the correlation between the cholinergic signaling pathway with other risk factors in AD and provides the latest research about the efficient therapeutic drugs and treatment of AD.

Keywords: Alzheimer’s disease; cholinergic signaling; drugs and treatment of Alzheimer’s disease; neurodegenerative disease.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic diagram of choline neurotransmission. ACh is synthesized by choline acetylcholine transferase (ChAT) from the cytoplasm of cholinergic presynaptic neurons by acetyl-coA and choline acetylcholine transferase. It is then transferred to synaptic vesicular follicles via vesicular acetylcholine transporter (VAChT). Depolarization of presynaptic neurons promotes extracellular secretion of ACh, which can then bind to nicotine or muscarinic receptors, leading to stimulatory or inhibitory responses. AChE rapidly hydrolyzes acetylcholine at the synaptic cleft, releasing acetate and choline, which are reabsorbed by the high-affinity choline transporter (CHT1) into presynaptic cholinergic neurons.
Figure 2
Figure 2
Schematic diagram of AChEI. ACh released from the presynaptic membrane into the synaptic cleft is normally rapidly hydrolyzed by AChE into choline. Choline is re-ingested by the presynaptic neuron to synthesize new ACh. People with AD have deficiency of ACh, and the levels of ACh in their brains are much lower than in normal people. AChEIs can inhibit the activity of AChE and thus block the hydrolysis of ACh, which can increase the concentration of ACh in the synaptic clefts and prolong the duration of ACh action in order to alleviate the cognitive impairment of AD patients. A, B, C, D, E refer to step A, B, C, D, E, which are the processes by which ACh is synthesized and metabolized in the body.
Figure 3
Figure 3
Some drugs related with the treatment of AD.
See this image and copyright information in PMC

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