NR AWNQ
AU Sikorska,B.; Liberski,P.P.; Giraud,P.; Kopp,N.; Brown,P.
TI Autophagy is a common ultrastructural feature of transmissible spongiform encephalopathies
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions PA-51
PT Konferenz-Poster
AB Autophagy is a process by which subcellular constituents and organelles are targeted for degradation in lysosomes. In macroautophagy, proteins and organelles are sequestrated into a double membrane bound vacuole called autophagosome, formed by ER membranes, under the direction of various proteins including MAP-LC3 - a microtubule associated protein - light chain 3, and several Apg proteins. In addition to maintaining cellular homeostasis, autophagy may also contribute to cell damage. It is involved in autophagic programmed cell death, called programmed cell death type II. The role of autophagy in neurodegeneration is not only in removing protein aggregates but also in inducing the death of neurons. To date, electron microscopy has been the best reliable method for monitoring autophagy. The presence of autophagic vacuoles in experimentally induced scrapie, Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker syndrome as well as in human prion diseases has been described. We studied the ultrastructural signs of autophagy in prion diseases: in brain biopsies from Creutzfeldt-Jakob disease and fatal familial insomnia patients and in experimental scrapie in hamsters. Ultrastructurallly, several steps of autophagy can be observed. Initially, a part of the neuronal cytoplasm is sequestrated by concentric arrays of double membranes; the enclosed cytoplasm appears relatively normal except that its density is often increased. Next, electron density of the central area dramatically increases. The membranes then proliferate within the cytoplasm in a labyrinth-like manner and the area sequestrated by these membranes enlarges into a more complex structure consisting of vacuoles, electron-dense areas and areas of normally-looking cytoplasm connected by convoluted membranes. Of note, autophagic vacuoles formed not only in neuronal perikarya but also in neurites and synapses. Finally, a large area of the cytoplasm is transformed into a collection of autophagic vacuoles of different sizes. We have also observed many multivesicular bodies which are involved in the process of microautophagy. Although the role of autophagy in prion diseases remains unknown, at least three hypothesises must be taken into consideration; 1) autophagy plays a role in removing protein aggregates 2) autophagy in one of the ways of neuron death in prion diseases and 3) it may participate in a formation of spongiform change.
AD B. Sikorska, P.P. Liberski: Department of Molecular. Pathology and Neuropatholology, Medical University of Lodz, Lodz, Poland; P. Giraud, N. Kopp: Hopital Neurologique et Neuro-chirurgical Pierre Wertheimer, Laboratoire d'Anatomie Pathologique et de Neuropathologique, Lyon, France; P. Brown: Bethesda, Maryland, USA
SP englisch
PO Italien