Accumulation of exogenous amyloid- Beta peptide in hippocampal mitochondria causes their dysfunction: A protective role for melatonin

Sergio Rosales-Corral, Dario Acuna-Castroviejo, Dun Xian Tan, Gabriela López-Armas, José Cruz-Ramos, Rubén Munoz, Valery G. Melnikov, Lucien C. Manchester, Russel J. Reiter

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37 Scopus citations

Abstract

Amyloid-beta (Aβ) pathology is related to mitochondrial dysfunction accompanied by energy reduction and an elevated production of reactive oxygen species (ROS). Monomers and oligomers of Aβ have been found inside mitochondria where they accumulate in a time-dependent manner as demonstrated in transgenic mice and in Alzheimer's disease (AD) brain. We hypothesize that the internalization of extracellular Aβ aggregates is the major cause of mitochondrial damage and here we report that following the injection of fibrillar Aβ into the hippocampus, there is severe axonal damage which is accompanied by the entrance of Aβ into the cell. Thereafter, Aβ appears in mitochondria where it is linked to alterations in the ionic gradient across the inner mitochondrial membrane. This effect is accompanied by disruption of subcellular structure, oxidative stress, and a significant reduction in both the respiratory control ratio and in the hydrolytic activity of ATPase. Orally administrated melatonin reduced oxidative stress, improved the mitochondrial respiratory control ratio, and ameliorated the energy imbalance.

Original languageEnglish (US)
Article number843649
JournalOxidative Medicine and Cellular Longevity
DOIs
StatePublished - 2012

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Cell Biology

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    Rosales-Corral, S., Acuna-Castroviejo, D., Tan, D. X., López-Armas, G., Cruz-Ramos, J., Munoz, R., Melnikov, V. G., Manchester, L. C., & Reiter, R. J. (2012). Accumulation of exogenous amyloid- Beta peptide in hippocampal mitochondria causes their dysfunction: A protective role for melatonin. Oxidative Medicine and Cellular Longevity, [843649]. https://doi.org/10.1155/2012/843649