title: Acetyl-CoA the key factor for survival or death of cholinergic neurons in course of neurodegenerative diseases.
abstract: Glucose-derived pyruvate is a principal source of acetyl-CoA in all brain cells, through pyruvate dehydogenase complex (PDHC) reaction. Cholinergic neurons like neurons of other transmitter systems and glial cells, utilize acetyl-CoA for energy production in mitochondria and diverse synthetic pathways in their extramitochondrial compartments. However, cholinergic neurons require additional amounts of acetyl-CoA for acetylcholine synthesis in their cytoplasmic compartment to maintain their transmitter functions. Characteristic feature of several neurodegenerating diseases including Alzheimer's disease and thiamine diphosphate deficiency encephalopathy is the decrease of PDHC activity correlating with cholinergic deficits and losses of cognitive functions. Such conditions generate acetyl-CoA deficits that are deeper in cholinergic neurons than in noncholinergic neuronal and glial cells, due to its additional consumption in the transmitter synthesis. Therefore, any neuropathologic conditions are likely to be more harmful for the cholinergic neurons than for noncholinergic ones. For this reason attempts preserving proper supply of acetyl-CoA in the diseased brain, should attenuate high susceptibility of cholinergic neurons to diverse neurodegenerative conditions. This review describes how common neurodegenerative signals could induce deficts in cholinergic neurotransmission through suppression of acetyl-CoA metabolism in the cholinergic neurons.
authors.affiliation: Department of Laboratory Medicine, Medical University of Gdańsk, Ul. Dębinki 7, 80-211, Gdańsk, Poland. aszut@gumed.edu.pl
authors.forename: Andrzej
authors.initials: A
authors.lastname: Szutowicz
authors.forename: Hanna
authors.initials: H
authors.lastname: Bielarczyk
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jankowska-Kulawy
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Pawełczyk
authors.forename: Anna
authors.initials: A
authors.lastname: Ronowska
mesh_terms: D000105:Acetyl Coenzyme A / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D004734:Energy Metabolism; D006801:Humans; D019636:Neurodegenerative Diseases / Q000473:pathology*; D011950:Receptors, Cholinergic / Q000378:metabolism*
chemical_list: D011950:Receptors, Cholinergic; D000105:Acetyl Coenzyme A