Tau monomer encodes strains
| Autor: | Talitha L. Thomas, Da Nae R. Woodard, Apurwa M Sharma, Marc I. Diamond, Omar M. Kashmer |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Mouse law.invention Mice chemistry.chemical_compound law Protein Isoforms Corticobasal degeneration biosensor cell Lymphocytes Biology (General) Brain Mapping Strain (chemistry) Chemistry General Neuroscience Brain General Medicine Cell biology Monomer Tauopathies Disease Progression Recombinant DNA Medicine Female Tauopathy Prions QH301-705.5 Science Chemical biology Mice Transgenic tau Proteins Neuropathology Single strain General Biochemistry Genetics and Molecular Biology prion 03 medical and health sciences strain Biochemistry and Chemical Biology Cell Line Tumor medicine Animals Humans Protein Structure Quaternary Cell Proliferation Brain Chemistry General Immunology and Microbiology medicine.disease Molecular biology Clone Cells Disease Models Animal 030104 developmental biology Cell culture Tau Research Advance Neuroscience |
| Zdroj: | eLife, Vol 7 (2018) eLife |
| Popis: | Tauopathies have diverse presentation, progression, and neuropathology. They are linked to tau prion strains, self-replicating assemblies of unique quaternary conformation, whose origin is unknown. Strains can be propagated indefinitely in cultured cells, and induce unique patterns of transmissible neuropathology upon inoculation into mice. DS9 and DS10 cell lines propagate different synthetic strains that derive from recombinant tau. We previously observed that tau monomer adopts two conformational states: one that is inert (Mi) and one that is seed-competent (Ms) (Mirbaha et al., 2018). We have now found that Ms itself is comprised of multiple stable ensembles that encode unique strains. DS9 monomer inoculated into naive cells encoded only DS9, whereas DS10 monomer encoded multiple sub-strains. Sub-strains each induced distinct pathology upon inoculation into a tauopathy mouse model (PS19). Ms purified from an Alzeimer's disease brain encoded a single strain. Conversely, Ms from a corticobasal degeneration brain encoded three sub-strains, in which monomer from any one re-established all three upon inoculation into cells. Seed competent tau monomer thus adopts multiple, stable seed-competent conformations, each of which encodes a limited number of strains. This provides insight into the emergence of distinct tauopathies, and may improve diagnosis and therapy. |
| Databáze: | OpenAIRE |
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