Killing Me Softly: Connotations to Unfolded Protein Response and Oxidative Stress in Alzheimer’s Disease
Joint Authors
Orzechowski, Arkadiusz
Kania, Elżbieta
Pająk, Beata
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-01-06
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
This review is focused on the possible causes of mitochondrial dysfunction in AD, underlying molecular mechanisms of this malfunction, possible causes and known consequences of APP, Aβ, and hyperphosphorylated tau presence in mitochondria, and the contribution of altered lipid metabolism (nonsterol isoprenoids) to pathological processes leading to increased formation and accumulation of the aforementioned hallmarks of AD.
Abnormal protein folding and unfolded protein response seem to be the outcomes of impaired glycosylation due to metabolic disturbances in geranylgeraniol intermediary metabolism.
The origin and consecutive fate of APP, Aβ, and tau are emphasized on intracellular trafficking apparently influenced by inaccurate posttranslational modifications.
We hypothesize that incorrect intracellular processing of APP determines protein translocation to mitochondria in AD.
Similarly, without obvious reasons, the passage of Aβ and tau to mitochondria is observed.
APP targeted to mitochondria blocks the activity of protein translocase complex resulting in poor import of proteins central to oxidative phosphorylation.
Besides, APP, Aβ, and neurofibrillary tangles of tau directly or indirectly impair mitochondrial biochemistry and bioenergetics, with concomitant generation of oxidative/nitrosative stress.
Limited protective mechanisms are inadequate to prevent the free radical-mediated lesions.
Finally, neuronal loss is observed in AD-affected brains typically by pathologic apoptosis.
American Psychological Association (APA)
Pająk, Beata& Kania, Elżbieta& Orzechowski, Arkadiusz. 2016. Killing Me Softly: Connotations to Unfolded Protein Response and Oxidative Stress in Alzheimer’s Disease. Oxidative Medicine and Cellular Longevity،Vol. 2016, no. 2016, pp.1-17.
https://search.emarefa.net/detail/BIM-1113648
Modern Language Association (MLA)
Pająk, Beata…[et al.]. Killing Me Softly: Connotations to Unfolded Protein Response and Oxidative Stress in Alzheimer’s Disease. Oxidative Medicine and Cellular Longevity No. 2016 (2016), pp.1-17.
https://search.emarefa.net/detail/BIM-1113648
American Medical Association (AMA)
Pająk, Beata& Kania, Elżbieta& Orzechowski, Arkadiusz. Killing Me Softly: Connotations to Unfolded Protein Response and Oxidative Stress in Alzheimer’s Disease. Oxidative Medicine and Cellular Longevity. 2016. Vol. 2016, no. 2016, pp.1-17.
https://search.emarefa.net/detail/BIM-1113648
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1113648