Abstract
Mitochondria are dynamic ATP-generating organelle which contribute to many cellular functions including bioenergetics processes, intracellular calcium regulation, alteration of reduction-oxidation potential of cells, free radical scavenging, and activation of caspase mediated cell death. Mitochondrial functions can be negatively affected by amyloid β peptide (Aβ), an important component in Alzheimer's disease (AD) pathogenesis, and Aβ can interact with mitochondria and cause mitochondrial dysfunction. One of the most accepted hypotheses for AD onset implicates that mitochondrial dysfunction and oxidative stress are one of the primary events in the insurgence of the pathology. Here, we examine structural and functional mitochondrial changes in presence of Aβ. In particular we review data concerning Aβ import into mitochondrion and its involvement in mitochondrial oxidative stress, bioenergetics, biogenesis, trafficking, mitochondrial permeability transition pore (mPTP) formation, and mitochondrial protein interaction. Moreover, the development of AD therapy targeting mitochondria is also discussed.
Highlights
Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disorder characterized by impairment of cognitive function
Mitochondrial functions can be negatively affected by amyloid β peptide (Aβ), an important component in Alzheimer’s disease (AD) pathogenesis, and Aβ can interact with mitochondria and cause mitochondrial dysfunction
Extracellular or intracellular Aβ is imported into the mitochondria through the the outer membrane (TOM) machinery
Summary
Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disorder characterized by impairment of cognitive function. The neuropathology of AD concerns two neurodegenerative processes: amyloidogenesis, leading to the presence of extracellular amyloid β-peptide (Aβ) deposition, and neurofibrillary degeneration, corresponding to the formation of intracellular tangles composed of phosphorylated Tau protein [1]. The presence of these abnormal structures leads to neuronal dysfunction and cell death. We dissect different points in which the mitochondrial functionality could be affected by Aβ presence, producing evidence from studies on AD human postmortem brains as well as cellular and AD animal models.
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