Role of mitochondrial-mediated signaling pathways in Alzheimer disease and hypoxia.
Development of effective treatments for Alzheimer's disease is complicated by the poor understanding of its pathophysiology. Recent work suggests mitochondria may play a primary role in neurodegeneration, due to alterations in mitochondria turnover and that the brain is specifically susceptible, due to high energy demand. Mitochondria are the major source of cellular energy through oxidative phosphorylation and regulate intracellular calcium levels and survival pathways. Hypoxia has been implicated in several neurodegenerative diseases including Alzheimer's disease. During hypoxic events, mitochondrial complex III produces high levels of reactive oxygen species (ROS). These ROS seem to have a primary role in the regulation of the transcription factor hypoxia inducible factor 1alpha that triggers death effectors. Here we discuss the role of mitochondria in AD putting focus on the activation of hypoxia-mediated mitochondrial pathways, which could eventually lead to cell degeneration and death.
Carvalho
Cristina
C
Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Correia
Sónia C
SC
Santos
Renato X
RX
Cardoso
Susana
S
Moreira
Paula I
PI
Clark
Timothy A
TA
Zhu
Xiongwei
X
Smith
Mark A
MA
Perry
George
G
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016923:Cell Death; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D008959:Models, Neurological; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D017382:Reactive Oxygen Species