Aβ-globulomers are formed independently of the fibril pathway
| Autor: | Andreas Striebinger, Helga Byrnes, Heinz Hillen, Kathrin Ullrich, Reinhold Mueller, Gerald P. Gellermann, Stefan Barghorn |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Amyloid
Protein Conformation BACE1-AS Plaque Amyloid Biology Monocyte Fibril lcsh:RC321-571 Mice chemistry.chemical_compound Protein structure Alzheimer Disease Animals Senile plaques lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Cells Cultured Amyloid beta-Peptides In vitro toxicology P3 peptide Neurofibrillary Tangles Alzheimer's disease Conformational diseases Peptide Fragments Dementia Amyloid β-protein Congo red Biochemistry of Alzheimer's disease Mice Inbred C57BL Neurology chemistry Biochemistry Oligomers Astrocytes Biophysics Fibrils Signal Transduction |
| Zdroj: | Neurobiology of Disease, Vol 30, Iss 2, Pp 212-220 (2008) |
| ISSN: | 0969-9961 |
| DOI: | 10.1016/j.nbd.2008.01.010 |
| Popis: | Soluble A beta-oligomers are currently discussed as the major causative species for the development of Alzheimer's disease (AD). Consequently, the beta-amyloid cascade hypothesis was extended by A beta-oligomers and their central neuropathogenic role in AD. However, the molecular structure of A beta-oligomers and their relation to amyloid fibril formation remains elusive. Previously we demonstrated that incubation of A beta(1-42) with SDS or fatty acids induces the formation of a homogeneous globular A beta-oligomer termed A beta-globulomer. In this study we investigated the role of A beta-globulomers in the aggregation pathway of A beta-peptide. We used in vitro assays such as thioflavin-T binding and aggregation inhibitors like Congo red to reveal that A beta-peptide in its A beta-globulomer conformation is a structural entity which is independent from amyloid fibril formation. In addition, cellular Alzheimer's-like plaque forming assays show the resistance of A beta-globulomers to deposition as amyloid plaques. We hypothesize that a conformational switch of A beta is decisive for either fibril formation or alternatively and independently A beta-globulomer formation. |
| Databáze: | OpenAIRE |
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