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New Insights in the Amyloid-Beta Interaction with Mitochondria

DOI: 10.1155/2012/324968

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Biochemical and morphological alterations of mitochondria may play an important role in the pathogenesis of Alzheimer’s disease (AD). Particularly, mitochondrial dysfunction is a hallmark of amyloid-beta-induced neuronal toxicity in Alzheimer’s disease. The recent emphasis on the intracellular biology of amyloid-beta and its precursor protein (APP) has led researchers to consider the possibility that mitochondria-associated and mitochondrial amyloid-beta may directly cause neurotoxicity. Both proteins are known to localize to mitochondrial membranes, block the transport of nuclear-encoded mitochondrial proteins to mitochondria, interact with mitochondrial proteins, disrupt the electron transport chain, increase reactive oxygen species production, cause mitochondrial damage, and prevent neurons from functioning normally. In this paper, we will outline current knowledge of the intracellular localization of amyloid-beta. Moreover, we summarize evidence from AD postmortem brain as well as animal AD models showing that amyloid-beta triggers mitochondrial dysfunction through a number of pathways such as impairment of oxidative phosphorylation, elevation of reactive oxygen species production, alteration of mitochondrial dynamics, and interaction with mitochondrial proteins. Thus, this paper supports the Alzheimer cascade mitochondrial hypothesis such as the most important early events in this disease, and probably one of the future strategies on the therapy of this neurodegenerative disease. 1. Introduction Each year, over 10 million people globally suffer from neurodegenerative diseases. This figure is expected to grow by 20% over the next decade as the aging population increases and lives longer. This disease group is the fourth biggest killer in the developed world after heart diseases, cancer, and stroke [1]. The most common neurodegenerative diseases are AD, Parkinson disease, Lewy body dementia, frontotemporal dementia, and amyotrophic lateral sclerosis [2]. The most widely recognized is AD, which is among the principal debilitating conditions of the current century. Approximately 24 million people worldwide suffer from dementia, 60% of cases being due to AD, which occurs in 1% of individuals aged 50 to 70 years old and dramatically increases to 50% of those over 70 years old [3]. Dramatically, these numbers are estimated to increase to 15 million in the next 40 years [4]. From the neuropathological point of view, AD is characterized by selective neuronal loss, marked synaptic alteration, morphological mitochondrial abnormalities, and Tau pathology. The

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