Version 1
: Received: 15 December 2023 / Approved: 18 December 2023 / Online: 18 December 2023 (12:49:55 CET)
How to cite:
Varshavskaya, K.B.; Petrushanko, I.Y.; Mitkevich, V.A.; Barykin, E.P.; Makarov, A.A. Post-translational Modifications of Beta-Amyloid Alter Its Transport across the Blood-Brain Barrier. Preprints2023, 2023121326. https://doi.org/10.20944/preprints202312.1326.v1
Varshavskaya, K.B.; Petrushanko, I.Y.; Mitkevich, V.A.; Barykin, E.P.; Makarov, A.A. Post-translational Modifications of Beta-Amyloid Alter Its Transport across the Blood-Brain Barrier. Preprints 2023, 2023121326. https://doi.org/10.20944/preprints202312.1326.v1
Varshavskaya, K.B.; Petrushanko, I.Y.; Mitkevich, V.A.; Barykin, E.P.; Makarov, A.A. Post-translational Modifications of Beta-Amyloid Alter Its Transport across the Blood-Brain Barrier. Preprints2023, 2023121326. https://doi.org/10.20944/preprints202312.1326.v1
APA Style
Varshavskaya, K.B., Petrushanko, I.Y., Mitkevich, V.A., Barykin, E.P., & Makarov, A.A. (2023). Post-translational Modifications of Beta-Amyloid Alter Its Transport across the Blood-Brain Barrier. Preprints. https://doi.org/10.20944/preprints202312.1326.v1
Chicago/Turabian Style
Varshavskaya, K.B., Evgeny P. Barykin and Alexander A. Makarov. 2023 "Post-translational Modifications of Beta-Amyloid Alter Its Transport across the Blood-Brain Barrier" Preprints. https://doi.org/10.20944/preprints202312.1326.v1
Abstract
One of the hallmarks of Alzheimer’s disease (AD) is the accumulation of beta-amyloid peptide (Aβ) leading to formation of soluble neurotoxic Aβ oligomers and insoluble amyloid plaques in various parts of the brain. Aβ undergoes post-translational modifications that alter its pathogenic properties. Aβ is produced not only in brain, but also in the peripheral tissues. Such Aβ, including its post-translationally modified forms, can enter the brain from circulation by binding to RAGE and contribute to the pathology of AD. However, the transport of modified forms of Aβ across the blood–brain barrier (BBB) has not been investigated. Here, we used a transwell BBB model as a controlled environment for permeability studies. We found that Aβ42 containing isomerized Asp7 residue (iso-Aβ42) and Aβ42 containing phosphorylated Ser8 residue crossed the BBB better than unmodified Aβ42, which correlated with different contribution of endocytosis mechanisms to the transport of these isoforms. Using microscale thermophoresis, we observed that RAGE binds to iso-Aβ42 an order of magnitude weaker than to Aβ42. Thus, post-translational modifications of Aβ increase the rate of its transport across the BBB and modify the mechanisms of the transport, which may be important for AD pathology and treatment.
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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