title: Early and Late Pathomechanisms in Alzheimer's Disease: From Zinc to Amyloid-β Neurotoxicity.
abstract: There are several systemic and intracerebral pathologic conditions, which limit provision and utilization of energy precursor metabolites in neuronal cells. Energy deficits cause excessive depolarization of neuronal cells triggering glutamate-zinc evoked excitotoxic cascade. The intracellular zinc excess hits several intraneuronal targets yielding collapse of energy balance and impairment functional and structural impairments cholinergic neurons. Disturbances in metabolism of acetyl-CoA, which is a direct precursor for energy, acetylcholine, N-acetyl-L-aspartate and acetylated proteins synthesis, play an important role in these pathomechanisms. Disruption of brain homeostasis activates slow accumulation of amyloid-β1-42, which extra and intracellular oligomeric deposits disrupt diverse transporting and signaling processes in all membrane structures of the cell. Both neurotoxic signals may combine aggravating detrimental effects on neuronal cell. Different neuroglial and neuronal cell types may display differential susceptibility to similar pathogenic insults depending on specific features of their energy and functional parameters. This review, basing on findings gained from cellular and animal models of Alzheimer's disease, discusses putative energy/acetyl-CoA dependent mechanism in early and late stages of neurodegeneration.
authors.affiliation: Department of Laboratory Medicine, Medical University of Gdańsk, Ul. Dębinki 7, 80-211, Gdansk, Poland. aszut@gumed.edu.pl.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Szutowicz
authors.affiliation: Department of Laboratory Medicine, Medical University of Gdańsk, Ul. Dębinki 7, 80-211, Gdansk, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Bielarczyk
authors.affiliation: Department of Laboratory Medicine, Medical University of Gdańsk, Ul. Dębinki 7, 80-211, Gdansk, Poland.
authors.forename: Marlena
authors.initials: M
authors.lastname: Zyśk
authors.affiliation: Department of Laboratory Medicine, Medical University of Gdańsk, Ul. Dębinki 7, 80-211, Gdansk, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Dyś
authors.affiliation: Department of Laboratory Medicine, Medical University of Gdańsk, Ul. Dębinki 7, 80-211, Gdansk, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Ronowska
authors.affiliation: Department of Laboratory Medicine, Medical University of Gdańsk, Ul. Dębinki 7, 80-211, Gdansk, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Gul-Hinc
authors.affiliation: Department of Laboratory Medicine, Medical University of Gdańsk, Ul. Dębinki 7, 80-211, Gdansk, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Klimaszewska-Łata
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004734:Energy Metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D011768:Pyruvate Dehydrogenase Complex; D000105:Acetyl Coenzyme A; D015032:Zinc
keywords: Acetyl-CoA; Alzheimer’s disease; Amyloid-β; Cholinergic system; Energy metabolism; Zinc