Copper, Iron, Selenium and Lipo-Glycemic Dysmetabolism in Alzheimer's Disease.
Int J Mol Sci
; 22(17)2021 Aug 31.
Article
en En
| MEDLINE
| ID: mdl-34502369
ABSTRACT
The aim of the present review is to discuss traditional hypotheses on the etiopathogenesis of Alzheimer's disease (AD), as well as the role of metabolic-syndrome-related mechanisms in AD development with a special focus on advanced glycation end-products (AGEs) and their role in metal-induced neurodegeneration in AD. Persistent hyperglycemia along with oxidative stress results in increased protein glycation and formation of AGEs. The latter were shown to possess a wide spectrum of neurotoxic effects including increased Aß generation and aggregation. In addition, AGE binding to receptor for AGE (RAGE) induces a variety of pathways contributing to neuroinflammation. The existing data also demonstrate that AGE toxicity seems to mediate the involvement of copper (Cu) and potentially other metals in AD pathogenesis. Specifically, Cu promotes AGE formation, AGE-Aß cross-linking and up-regulation of RAGE expression. Moreover, Aß glycation was shown to increase prooxidant effects of Cu through Fenton chemistry. Given the role of AGE and RAGE, as well as metal toxicity in AD pathogenesis, it is proposed that metal chelation and/or incretins may slow down oxidative damage. In addition, selenium (Se) compounds seem to attenuate the intracellular toxicity of the deranged tau and Aß, as well as inhibiting AGE accumulation and metal-induced neurotoxicity.
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1
Banco de datos:
MEDLINE
Asunto principal:
Productos Finales de Glicación Avanzada
/
Enfermedad de Alzheimer
Tipo de estudio:
Etiology_studies
Límite:
Humans
Idioma:
En
Año:
2021
Tipo del documento:
Article