NR AWPE
AU Trifilo,M.J.; Yajima,T.; Sanchez,M.; Peterson,K.L.; Race,R.E.; White,K.; Knowlton,K.U.; Chesebro,B.; Oldstone,M.B.A.
TI Prion-induced amyloid heart disease with high blood infectivity
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Oral sessions ORAL-31
PT Konferenz-Vortrag
AB Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of infectious diseases that cause neurodegeneration and death. The majority (>95%) of normal host derived prion protein (PrPsen) exists as a membrane bound, glycophosphatydilinositol (GPI) anchored protein. We recently (Science 2005, vol.308) constructed transgenic (tg) mice where the C-terminal 21 amino acids were not transcribed, resulting in a secreted form of PrPsen in which >98% of that molecule existed in a soluble non-membrane bound form. Intracerebral inoculation of these tg mice with numerous murine scrapie strains (RML, ME7, 22L) resulted in amyloid deposition in the brain and excessive buildup of abnormal folded prion protein (PrPres) in the absence of overt disease manifestations normally associated with scrapie over 700 days post infection (dpi). However, aberrant physiologic events in terms of delayed neural transmission and loss of long term potentiation could be found within 150 days post infection. Novel distribution patterns of PrPres within and around endothelial cells lining blood vessels occurred within the brain. Examination of blood demonstrated that both infectivity and PrPres could be readily detected by 280 dpi in both serum and cellular fractions of RML scrapie infected tg mice. Moreover, multiple extraneural tissues, such as spleen heart lunge, pancreas, and kidney, also showed PrPres deposition. Focus on the heart indicated that similar to brain, deposits of both PrPres and amyloid that was infectious occurred. The deposition of amyloidogenic PrPres within the hearts of scrapie-infected tg mice resulted in disordered cardiac function including dramatic alterations in both systolic (reduced compliance) and diastolic (stiffening of the heart) function.
AD M.J. Trifilo, M. Sanchez, M.B.A. Oldstone: Viral-Immunobiology Laboratory, Departments of Molecular and Integrative Neurosciences and Infectology, Scripps Research Institute, La Jolla, CA, USA; T. Yajima, K.L. Peterson, K. Knowlton: Department of Medicine, University of California, San Diego, La Jolla, CA, USA; R.E. Race, K. White, B. Chesebro: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT, USA; Departments of Neurosciences and Pathology, University of California, San Diego, CA, USA. E-mail: mtrifilo@scripps.edu
SP englisch
PO Italien