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.
Wang
Xinglong
X
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Su
Bo
B
Perry
George
G
Smith
Mark A
MA
Zhu
Xiongwei
X
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