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-β _1-42 , which extra and intracellular oligomeric deposits disrup

SUBMITTER: Szutowicz A 

PROVIDER: S-EPMC5357490 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature