The role of endoplasmic reticulum in amyloid precursor protein processing and trafficking: implications for Alzheimer's disease.
The endoplasmic reticulum (ER) is the principal organelle responsible for the proper folding/processing of nascent proteins and perturbed ER function leads to a state known as ER stress. Mammalian cells try to overcome ER stress through a set of protein signaling pathways and transcription factors termed the unfolded protein response (UPR). However, under unresolvable ER stress conditions, the UPR is hyperactivated inducing cell dysfunction and death. The accumulation of misfolded proteins in the brain of Alzheimer's disease (AD) patients suggests that alterations in ER homeostasis might be implicated in the neurodegenerative events that characterize this disorder. This review discusses the involvement of ER stress in the pathogenesis of AD, focusing the processing and trafficking of the AD-related amyloid precursor protein (APP) during disease development. The potential role of ER as a therapeutic target in AD will also be debated.
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
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Plácido
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
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Pereira
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
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Duarte
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
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Candeias
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
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Correia
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Department of Life Sciences, University of Coimbra, Coimbra, Portugal.
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Santos
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
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Carvalho
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
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Cardoso
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
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Oliveira
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal. Electronic address: venta@ci.uc.pt.
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Moreira
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D021381:Protein Transport
D016564:Amyloid beta-Protein Precursor
Alzheimer's disease; amyloid precursor protein; endoplasmic reticulum; secretory pathway; therapeutic targets; trafficking