Dementing and degenerative neurological deseases are responsible for many decastating human illnesses. As medical science has become progressively more successful, more people are living to an older age. With this change in demography has come an epidemic of a previously insignificant disorder-senile dementia. Most cases of senile dementia are due to Alzheimer's disease (AD). Not only is the cause of AD unknown, but there is no specific diagnostic test, and there is no effective treatment. The possible causes of AD include: a slow virus-like agent, a genetic disorder, accumulation of a toxin, or production of an abnormal metabolite. The many similarities between Creutzfeldt-Jakob disease (CJD) and AD have raised the possibility that a slow infectious agent might be the cause of AD; however, all attempts to transmit AD to laboratory animals have been disappointing. Recent progress has shown that a protein is required for the infectivity of the agent causing CJD and a similar neuodegenerative disease of sheep and goats, scrapie. Because the dominant molecular characteristics of these slow agents are those of a protein, and they are different from both viruses and viroids, we have chosen to label them """"""""prions"""""""" Understanding the molecular structure of slow infectious pathogens such as prions, which cause both scrapie and CJD, may help us to understand the etiology of not only AD, but also other devastating degenerative diseases of unknown etiology which afflict primarily older people. Improved purification protocols led to the identification of a 27-30 kDs protein that is a component of the scrapie prion. The unique molecular properties of the scrapie agent, or prion, appear to have defined a new class of small infectious pathogens. In this proposal, we outline studies designed to elucidate 1) the complete chemical structures of the cellular and scrapie prion proteins, 2) the molecular mechanisms of scrapie pathogenesis, 3) the cellular metabolism of the scrapie and cellular prion proteins, and 4) structure of scrapie and CJD may become the most well understood neurodegenerative diseases.
| 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 |
| 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 |
| Wang, Tuo; Jo, Hyunil; DeGrado, William F et al. (2017) Water Distribution, Dynamics, and Interactions with Alzheimer's ?-Amyloid Fibrils Investigated by Solid-State NMR. J Am Chem Soc 139:6242-6252 |
| Giles, Kurt; Woerman, Amanda L; Berry, David B et al. (2017) Bioassays and Inactivation of Prions. Cold Spring Harb Perspect Biol 9: |
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