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The differential spread of prion strains into the brain (153.1)
Author(s) -
Sigurdson Christina,
Bett Cyrus,
Kurt Tim,
Kong Qingzhong,
Nilsson K. Peter,
Masliah Eliezer,
Oldstone Michael
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.153.1
Subject(s) - spleen , prion protein , biology , human brain , in vivo , infectious agent , virology , amyloid (mycology) , pathology , neuroscience , disease , immunology , medicine , genetics , botany
Prions are the only protein aggregates that naturally transmit as infectious agents, and recently human to human transmission has occurred through transfusion of prion‐contaminated blood. Most cases of natural transmission start with a peripheral exposure followed by prion spread to the CNS. Yet certain prions do not invade the CNS, despite prion accumulation in non‐neural organs, such as spleen or heart. Intriguingly, all of these poorly neuroinvasive prions form fibrils, which are uncommon structures in prion disease. We are investigating the molecular basis for the remarkable differences between the spread of nonfibrillar and fibrillar prions to the brain using in vivo models. We have found that the fibrillar prions were more resistant to enzyme digestion and were extraordinarily stable when exposed to protein denaturing conditions, in mice and in humans. Taken together, these results provide evidence for a striking separation in the biochemical of fibrillar and nonfibrillar prions that underlie their differences in neuroinvasion. Grant Funding Source : NIH NS069566 and NS076896