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Pharmacokinetics and Molecular Modeling Indicate nAChRα4-Derived Peptide HAEE Goes through the Blood–Brain Barrier
| Content Provider | MDPI |
|---|---|
| Author | Zolotarev, Yurii Mitkevich, Vladimir Shram, Stanislav Adzhubei, Alexei Tolstova, Anna Talibov, Oleg Dadayan, Alexander Myasoyedov, Nikolai Makarov, Alexander Kozin, Sergey |
| Copyright Year | 2021 |
| Description | One of the treatment strategies for Alzheimer’s disease (AD) is based on the use of pharmacological agents capable of binding to beta-amyloid (Aβ) and blocking its aggregation in the brain. Previously, we found that intravenous administration of the synthetic tetrapeptide Acetyl-His-Ala-Glu-Glu-Amide (HAEE), which is an analogue of the 35–38 region of the α4 subunit of α4β2 nicotinic acetylcholine receptor and specifically binds to the 11–14 site of Aβ, reduced the development of cerebral amyloidogenesis in a mouse model of AD. In the current study on three types of laboratory animals, we determined the biodistribution and tissue localization patterns of HAEE peptide after single intravenous bolus administration. The pharmacokinetic parameters of HAEE were established using uniformly tritium-labeled HAEE. Pharmacokinetic data provided evidence that HAEE goes through the blood–brain barrier. Based on molecular modeling, a role of LRP1 in receptor-mediated transcytosis of HAEE was proposed. Altogether, the results obtained indicate that the anti-amyloid effect of HAEE, previously found in a mouse model of AD, most likely occurs due to its interaction with Aβ species directly in the brain. |
| Starting Page | 909 |
| e-ISSN | 2218273X |
| DOI | 10.3390/biom11060909 |
| Journal | Biomolecules |
| Issue Number | 6 |
| Volume Number | 11 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-06-18 |
| Access Restriction | Open |
| Subject Keyword | Biomolecules Hematology Alzheimer's Disease Beta-amyloid Α4β2 Nicotinic Acetylcholine Receptor Peptide Drug Blood–brain Barrier Receptor-mediated Transcytosis Lrp1 |
| Content Type | Text |
| Resource Type | Article |
