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
. 2017 May 15:8:58.
doi: 10.3389/fgene.2017.00058. eCollection 2017.

Amyloid β Modification: A Key to the Sporadic Alzheimer's Disease?

Evgeny P Barykin  1 , Vladimir A Mitkevich  1 , Sergey A Kozin  1 , Alexander A Makarov  1
Affiliations

Amyloid β Modification: A Key to the Sporadic Alzheimer's Disease?

Evgeny P Barykin et al. Front Genet. .
No abstract available

Keywords: Aging; Sporadic Alzheimer's disease; beta amyloid; post-translational Modifications (PTM); proteinopathies; proteostasis.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Pathways of Aβ modification. Aβ is a product of amyloid precursor protein (APP) cleavage at the plasma membrane or inside the cell in the endosomal compartment or ER/Golgi. These two pools exchange Aβ via endo- and exocytosis. Aβ in both of these pools can undergo oxidation due to interaction with reactive oxygen species (ROS) produced by NADPH-oxidase (NOX), the mitochondrial respiratory chain, or exogenous sources. Reactive nitrogen species (RNS) produced by nitric oxide synthase (NOS) isoforms also interact with Aβ which, results in nitration of the Tyr10 residue or formation of covalently linked dimers of Aβ. Extracellular Aβ is phosphorylated by extracellular protein kinase A (PKAex) and intracellular Aβ is subjected to phosphorylation by both intracellular PKA (PKAin) and cdc2 kinase (Cdk1). An exclusive modification of intracellular Aβ is citrullination by peptidyl arginyl deiminase (PAD). Aspartic residues of Aβ are prone to spontaneous isomerization or racemization, and this isomerization can be reversed by protein carboxyl methyltransferase 1 (PCMT1). In amyloid deposits (plaques or multivesicular bodies [MVB]), Aβ undergoes oxidative damage which leads to the formation of adducts with 4-hydroxynonenal (HNE); a product of lipid peroxidation. Aminopeptidase A (ENPEP) and meprin can truncate Aβ. Lastly, amyloid beta can be pyroglutamylated at the E3 and E11 sites by glutaminyl-peptide cyclotransferase (QPCT).
See this image and copyright information in PMC

References

    1. Akomolafe A., Lunetta K., Erlich P., Cupples L., Baldwin C., Huyck M., et al. (2006). Genetic association between endothelial nitric oxide synthase and Alzheimer disease. Clin. Genet. 70, 49–56. 10.1111/j.1399-0004.2006.00638.x - DOI - PubMed
    1. Al-Hilaly Y. K., Williams T. L., Stewart-Parker M., Ford L., Skaria E., Cole M., et al. (2013). A central role for dityrosine crosslinking of Amyloid-β in Alzheimer's disease. Acta Neuropathol. Commun. 1:83. 10.1186/2051-5960-1-83 - DOI - PMC - PubMed
    1. Barykin E. P., Petrushanko I. Y., Burnysheva K. M., Makarov A. A., Mitkevich V. A. (2016). [Isomerization of Asp7 increases the toxic effects of amyloid beta and its phosphorylated form in SH-SY5Y neuroblastoma cells]. Mol. Biol. Mosk. 50, 863–869. 10.7868/S0026898416050037 - DOI - PubMed
    1. Bergem A. L. M. (1994). Heredity in dementia of the Alzheimer type. Clin. Genet. 46, 144–149. 10.1111/j.1399-0004.1994.tb04216.x - DOI - PubMed
    1. Bertram L., Lill C. M., Tanzi R. E. (2010). The Genetics of Alzheimer Disease: back to the future. Neuron 68, 270–281. 10.1016/j.neuron.2010.10.013 - DOI - PubMed