Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Jul:133:71-79.
doi: 10.1016/j.brainresbull.2016.08.009. Epub 2016 Aug 18.

Amyloid precursor protein processing and bioenergetics

Heather M Wilkins  1 , Russell H Swerdlow  2
Affiliations
Review

Amyloid precursor protein processing and bioenergetics

Heather M Wilkins et al. Brain Res Bull. 2017 Jul.

Abstract

The processing of amyloid precursor protein (APP) to amyloid beta (Aβ) is of great interest to the Alzheimer's disease (AD) field. Decades of research define how APP is altered to form Aβ, and how Aβ generates oligomers, protofibrils, and fibrils. Numerous signaling pathways and changes in cell physiology are known to influence APP processing. Existing data additionally indicate a relationship exists between mitochondria, bioenergetics, and APP processing. Here, we review data that address whether mitochondrial function and bioenergetics modify APP processing and Aβ production.

Keywords: Alpha secretase; Alzheimer's disease; Amyloid beta; Amyloid precursor protein; BACE1; Bioenergetics; Gamma secretase; Mitochondria.

PubMed Disclaimer

Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

Figure 1
Figure 1. APP Processing Pathways
The non-amyloidogenic pathway begins with cleavage of full-length APP (membrane bound) by α-secretase, yielding sAPPα (ectodomain; released to extracellular space) and CTF83 (membrane bound). CTF83 is then cleaved by γ-secretase (three consecutive cleavage sites) to generate p3 (released to extracellular space) and AICD (released to cytoplasm). The amyloidogenic pathway begins with cleavage of full-length APP (membrane bound) by β-secretase, yielding sAPPβ (ectodomain; released to extracellular space) and CTF99 (membrane bound). CTF99 is then cleaved by γ-secretase (three consecutive cleavage sites) to generate Aβ (released to extracellular space) and AICD (released to cytoplasm).
Figure 2
Figure 2. Mitochondrial function and bioenergetic intermediates influence APP Processing Pathways
Mitochondrial function and bioenergetic pathways (probably through intermediates, such as ROS, ATP, membrane potential, and NAD/NADH for example) can increase or decrease amyloidogenic and non-amyloidogenic APP processing. PM=plasma membrane.
See this image and copyright information in PMC

References

    1. Aho L, et al. Immunohistochemical visualization of amyloid-beta protein precursor and amyloid-beta in extra- and intracellular compartments in the human brain. J Alzheimers Dis. 2010;20:1015–1028. - PubMed
    1. Allinson TM, et al. ADAMs family members as amyloid precursor protein alpha-secretases. J Neurosci Res. 2003;74:342–352. - PubMed
    1. Anandatheerthavarada HK, et al. Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial function in neuronal cells. J Cell Biol. 2003;161:41–54. - PMC - PubMed
    1. Asai M, et al. Putative function of ADAM9, ADAM10, and ADAM17 as APP alpha-secretase. Biochem Biophys Res Commun. 2003;301:231–235. - PubMed
    1. Barrientos A, et al. Reduced steady-state levels of mitochondrial RNA and increased mitochondrial DNA amount in human brain with aging. Brain Res Mol Brain Res. 1997;52:284–289. - PubMed

MeSH terms

Substances

LinkOut - more resources