Title:Amyloid Beta Peptide-Mediated Alterations in Mitochondrial Dynamics
and its Implications for Alzheimer’s Disease
Volume: 22
Issue: 7
Author(s): Luis Ángel Monsalvo-Maraver, Marisol Maya-López, Edgar Rangel-López, Isaac Túnez, Alexey A. Tinkov, Anatoly Skalny, Beatriz Ferrer, Michael Aschner*Abel Santamaría*
Affiliation:
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
- Laboratorio de Aminoácidos Excitadores/Laboratorio de Neurofarmacología Molecular y Nanotecnología, Instituto
Nacional de Neurología y Neurocirugía, Mexico City 14269, Mexico
Keywords:
Amyloid beta-peptide, protein aggregation, mitochondrial function, energy metabolism alterations, mitophagy, neurodegeneration, Alzheimer’s disease.
Abstract: Alzheimer’s disease (AD) is considered the most frequent neurodegenerative disorder
worldwide, compromising cognitive function in patients, with an average incidence of 1-3% in the
open population. Protein aggregation into amyloidogenic plaques and neurofibrillary tangles, as well
as neurodegeneration in the hippocampal and cortical areas, represent the neuropathological hallmarks
of this disorder. Mechanisms involved in neurodegeneration include protein misfolding, augmented
apoptosis, disrupted molecular signaling pathways and axonal transport, oxidative stress, inflammation,
and mitochondrial dysfunction, among others. It is precisely through a disrupted energy metabolism
that neural cells trigger toxic mechanisms leading to cell death. In this regard, the study of mitochondrial
dynamics constitutes a relevant topic to decipher the role of mitochondrial dysfunction in
neurological disorders, especially when considering that amyloid-beta peptides can target mitochondria.
Specifically, the amyloid beta (Aβ) peptide, known to accumulate in the brain of AD patients, has
been shown to disrupt overall mitochondrial metabolism by impairing energy production, mitochondrial
redox activity, and calcium homeostasis, thus highlighting its key role in the AD pathogenesis. In
this work, we review and discuss recent evidence supporting the concept that mitochondrial dysfunction
mediated by amyloid peptides contributes to the development of AD.
