| First Author | Kozin SA | Year | 2018 |
| Journal | Front Neurosci | Volume | 12 |
| Pages | 518 | PubMed ID | 30210271 |
| Mgi Jnum | J:311604 | Mgi Id | MGI:6771798 |
| Doi | 10.3389/fnins.2018.00518 | Citation | Kozin SA, et al. (2018) Intravenously Injected Amyloid-beta Peptide With Isomerized Asp7 and Phosphorylated Ser8 Residues Inhibits Cerebral beta-Amyloidosis in AbetaPP/PS1 Transgenic Mice Model of Alzheimer's Disease. Front Neurosci 12:518 |
| abstractText | Cerebral beta-amyloidosis, an accumulation in the patient's brain of aggregated amyloid-beta (Abeta) peptides abnormally saturated by divalent biometal ions, is one of the hallmarks of Alzheimer's disease (AD). Earlier, we found that exogenously administrated synthetic Abeta with isomerized Asp7 (isoD7-Abeta) induces Abeta fibrillar aggregation in the transgenic mice model of AD. IsoD7-Abeta molecules have been implied to act as seeds enforcing endogenous Abeta to undergo pathological aggregation through zinc-mediated interactions. On the basis of our findings on zinc-induced oligomerization of the metal-binding domain of various Abeta species, we hypothesize that upon phosphorylation of Ser8, isoD7-Abeta loses its ability to form zinc-bound oligomeric seeds. In this work, we found that (i) in vitro isoD7-Abeta with phosphorylated Ser8 (isoD7-pS8-Abeta) is less prone to spontaneous and zinc-induced aggregation in comparison with isoD7-Abeta and intact Abeta as shown by thioflavin T fluorimetry and dynamic light scattering data, and (ii) intravenous injections of isoD7-pS8-Abeta significantly slow down the progression of institutional beta-amyloidosis in AbetaPP/PS1 transgenic mice as shown by the reduction of the congophilic amyloid plaques' number in the hippocampus. The results support the role of the zinc-mediated oligomerization of Abeta species in the modulation of cerebral beta-amyloidosis and demonstrate that isoD7-pS8-Abeta can serve as a potential molecular tool to block the aggregation of endogenous Abeta in AD. |
