Data Entry: Please note that the research database will be replaced by UNIverse by the end of October 2023. Please enter your data into the system https://universe-intern.unibas.ch. Thanks
Mitochondrial dysfunction is a hallmark of amyloid-beta(A?)-induced neuronal toxicity in Alzheimer's disease (AD). The recent emphasis on the intracellular biology of A? and its precursor protein (A?PP) has led researchers to consider the possibility that mitochondria-associated and/or intramitochondrial A? may directly cause neurotoxicity. In this paper, we will outline current knowledge of the intracellular localization of both A? and A?PP addressing the question of how A? can access mitochondria. Moreover, we summarize evidence from AD postmortem brain as well as cellular and animal AD models showing that A? triggers mitochondrial dysfunction through a number of pathways such as impairment of oxidative phosphorylation, elevation of reactive oxygen species (ROS) production, alteration of mitochondrial dynamics, and interaction with mitochondrial proteins. In particular, we focus on A? interaction with different mitochondrial targets including the outer mitochondrial membrane, intermembrane space, inner mitochondrial membrane, and the matrix. Thus, this paper establishes a modified model of the Alzheimer cascade mitochondrial hypothesis.
