Insights into amyloid-beta-induced mitochondrial dysfunction in Alzheimer disease.
Amyloid-beta has long been implicated in the pathogenesis of Alzheimer disease. The focus was initially on the extracellular fibrillar deposits of amyloid-beta but more recently has shifted to intracellular oligomeric forms of amyloid-beta. Unfortunately, the mechanism(s) by which either extracellular or intracellular amyloid-beta induces neuronal toxicity remains unclear. That said, a number of recent studies indicate that mitochondria might be an important target of amyloid-beta. Neurons rely heavily on mitochondria for energy and it is well established that mitochondrial dysfunction might be an important target of amyloid-beta. Mechanistically, amyloid-beta aggregates in mitochondria to impair function, leading to energy hypometabolism and elevated reactive oxygen species production. Additionally, amyloid-beta affects the balance of mitochondrial fission/fusion and mitochondrial transport, negatively impacting a host of cellular functions of neurons. Here, we review the role that amyloid-beta plays in mitochondrial structure and function of neurons and the importance of this in the pathogenesis of Alzheimer disease.
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Xinglong
X
Wang
Bo
B
Su
George
G
Perry
Mark A
MA
Smith
Xiongwei
X
Zhu
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D046912:Multiprotein Complexes; D009474:Neurons / Q000378:metabolism
D016229:Amyloid beta-Peptides; D005609:Free Radicals; D046912:Multiprotein Complexes