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PrPSc Oligomerization Appears Dynamic, Quickly Engendering Inherent M1000 Acute Synaptotoxicity by Foliaki, Simote T.; Lewis, Victoria; Islam, Abu M.T.; Senesi, Matteo; Finkelstein, David I.; Ellett, Laura J.; Lawson, Victoria A.; Adlard, Paul A.; Roberts, Blaine R.; Collins, Steven J. is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is PrPSc Oligomerization Appears Dynamic, Quickly Engendering Inherent M1000 Acute Synaptotoxicity about?
Prion diseases are neurodegenerative disorders pathogenically linked to cellular prion protein (PrPC) misfolding into abnormal conformers (PrPSc), with PrPSc underpinning both transmission and synaptotoxicity. Although the biophysical features of PrPSc required to induce acute synaptic dysfunction remain incompletely defined, we recently reported that acutely synaptotoxic PrPSc appeared to be oligomeric. We herein provide further insights into the kinetic and requisite biophysical characteristics of acutely synaptotoxic ex vivo PrPSc derived from the brains of mice dying from M1000 prion disease. Pooled fractions of M1000 PrPSc located within the molecular weight range approximating monomeric PrP (mM1000) generated through size exclusion chromatography were found to harbor acute synaptotoxicity equivalent to preformed oligomeric fractions (oM1000). Subsequent investigation showed mM1000 corresponded to PrPSc rapidly concatenating in physiological buffer to exist as predominantly, closely associated, small oligomers. The oligomerization of PrP in mM1000 could be substantially mitigated by treatment with the antiaggregation compound epigallocatechin gallate, thereby maintaining the P
Who reads PrPSc Oligomerization Appears Dynamic, Quickly Engendering Inherent M1000 Acute Synaptotoxicity?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Foliaki, Simote T.; Lewis, Victoria; Islam, Abu M.T.; Senesi, Matteo; Finkelstein, David I.; Ellett, Laura J.; Lawson, Victoria A.; Adlard, Paul A.; Roberts, Blaine R.; Collins, Steven J.
- Publisher
- Biophysical Society; Elsevier ; Elsevier BV (ISSN 0006-3495)
- Published
- 2020
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)