At present, there is no treatment that prevents or even slows the progression of Alzheimer's disease (AD), which is the most prevalent neurodegenerative disorder. The Animal Core (Core C) will provide normal and genetically modified mice or rats and will conduct the experiments described in Projects 1, 2, and 3. Rodent models that express human proteins involved in neurodegenerative disease proved key in the discovery of misfolded forms of normal proteins, called prions, as new principles of disease. AD involves two prions, tau and Abeta. Cellular assays allow measurement of human tau and Abeta prions in culture, but transfer of disease from humans to mice will provide essential validation. Inoculation of brain homogenates into specific regions of the rodent brain and subsequent diagnosis of disease requires exceptionally skilled animal technicians who also assess disease onset by evaluating clinical signs and by bioluminescence as a marker of disease-induced gliosis in transgenic models specifically bred for this purpose (Projects 1 and 2). The stability of tau and Abeta prion strains or conformations also will be tested by repeated passage in mice (Project 2). Exceptionally high resolution structures (Project 3) can be determined by cryo-electron microscopy using material provided by Core C. The experiments executed in Core C ultimately will provide models to test therapies that halt disease progression.
| O'Brien, Connor J; Droege, Daniel G; Jiu, Alexander Y et al. (2018) Photoredox Cyanomethylation of Indoles: Catalyst Modification and Mechanism. J Org Chem 83:8926-8935 |
| Condello, Carlo; Lemmin, Thomas; Stöhr, Jan et al. (2018) Structural heterogeneity and intersubject variability of A? in familial and sporadic Alzheimer's disease. Proc Natl Acad Sci U S A 115:E782-E791 |
| Woerman, Amanda L; Kazmi, Sabeen A; Patel, Smita et al. (2018) MSA prions exhibit remarkable stability and resistance to inactivation. Acta Neuropathol 135:49-63 |
| Yang, Bing; Wu, Haifan; Schnier, Paul D et al. (2018) Proximity-enhanced SuFEx chemical cross-linker for specific and multitargeting cross-linking mass spectrometry. Proc Natl Acad Sci U S A 115:11162-11167 |
| Irimata, Katherine E; Dugger, Brittany N; Wilson, Jeffrey R (2018) Impact of the Presence of Select Cardiovascular Risk Factors on Cognitive Changes among Dementia Subtypes. Curr Alzheimer Res 15:1032-1044 |
| Nick, Mimi; Wu, Yibing; Schmidt, Nathan W et al. (2018) A long-lived A? oligomer resistant to fibrillization. Biopolymers 109:e23096 |
| Woerman, Amanda L; Watts, Joel C; Aoyagi, Atsushi et al. (2018) ?-Synuclein: Multiple System Atrophy Prions. Cold Spring Harb Perspect Med 8: |
| Woerman, Amanda L; Kazmi, Sabeen A; Patel, Smita et al. (2018) Familial Parkinson's point mutation abolishes multiple system atrophy prion replication. Proc Natl Acad Sci U S A 115:409-414 |
| Saltzberg, Daniel J; Broughton, Howard B; Pellarin, Riccardo et al. (2017) A Residue-Resolved Bayesian Approach to Quantitative Interpretation of Hydrogen-Deuterium Exchange from Mass Spectrometry: Application to Characterizing Protein-Ligand Interactions. J Phys Chem B 121:3493-3501 |
| Lee, Myungwoon; Wang, Tuo; Makhlynets, Olga V et al. (2017) Zinc-binding structure of a catalytic amyloid from solid-state NMR. Proc Natl Acad Sci U S A 114:6191-6196 |
Showing the most recent 10 out of 363 publications
