Acetyl-CoA the Key Factor for Survival or Death of Cholinergic Neurons in Course of Neurodegenerative Diseases

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 pathwa...

Full description

Saved in:
Bibliographic Details
Published in:Neurochemical research 2013-08, Vol.38 (8), p.1523-1542
Main Authors: Szutowicz, Andrzej, Bielarczyk, Hanna, Jankowska-Kulawy, Agnieszka, Pawełczyk, Tadeusz, Ronowska, Anna
Format: Article
Language:English
Subjects:
Acetyl Coenzyme A - physiology
Acetylcholine
Biochemistry
Biomedical and Life Sciences
Biomedicine
Brain - metabolism
Cell Biology
Cell Death - physiology
Cell Survival - physiology
Energy Metabolism
Humans
Neurochemistry
Neurodegenerative Diseases - pathology
Neurology
Neurosciences
Overview
Receptors, Cholinergic - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0364-3190
1573-6903
DOI:10.1007/s11064-013-1060-x