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Health See other Health Articles Title: Is Parkinson's a prion disease? Medscape... Is Parkinson's a prion disease? Prions are proteinaceous infectious agents responsible for the transmissible spongiform dementia syndromes, including CJD, mad-cow disease and Kuru. In all of these syndromes there is accumulation of amyloid composed of the PrP protein that is conformationally altered so that it is biochemically stable and these deposits are associated with neurodegeneration. In addition, there are several genetic diseases associated with mutations in the PrP protein that also have amyloid accumulations composed of the same protein. These remarkable observations have revolutionized the way that neurodegenerative diseases are understood but it has long been a question how these PrP-associated prion diseases might relate to the much more common and largely sporadic neurodegenerative diseases also marked by accumulations of entirely different proteins - eg Parkinson's and Alzheimer's. Over the last several years there has been accumulating evidence that there may be some signficiant similarities. One of the hallmarks of prion diseases is that the prion particles are able to self-propagate by changing the conformation of the normal versions of the prion proteins to allow reproduction of the amyloid forming confomers of the protein. Do the proteins that are deposited in other diseases share this characteristic? In a new study by Recasens et al in the Annals of Neurology (March 2014 issue) the authors have taken a major step forward in this area. The authors purified Lewy Body (LB) enriched fractions from the brains of Parkinson's patients and injected them into rodent and primate substantia nigra and found that this induces a progressive neurodegenerative phenotype in these experimental animals. LB are made up of modified alpha-synuclein that is abnormally stable forming insoluble protein aggregates in cells. The injection of the LB-enriched brain extracts (but not other extracts from the same brains) leads to the modification of host alpha-synuclein so that it forms deposits and propagates the neurdegenerative process. Does this mean that Parkinson's is infectious? Not at all really. There is no credible indication that LB-associated diseases are spread by an infectious route. More likely the conformational changes needed to allow self-propagation are either spontaneous with aging, associated with toxic environmental events or genetic (associated with sequence changes in the synuclein protein) that lead to formation of aggregates in a particular cell. This leads to a cyclic and accelerating process that may spread from cell to cell by internalization of externalized aggregates (after cell death), thus providing for a progressive course. Obviously there is great interest in determining to what extent this mechanism may explain the occurrence and progression of other neurodegenerative diseases associated with protein aggregates. 1 Comment #1, Added By: mrh57, MD, Neurology, This is certainly another piece of the puzzle and supports the work of Hansen et al from 2011. His group had published an eloquent model system transferring of ±-syn monomers and aggregates in both cell cultured neurons and and in situ in mouse brains. I suspect that many of the neuronal diseases that are associated with inclusion bodies will have etiologies related to stable aberrant proteins that are able to induce conformational changes and propagate pathologic forms. ±-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. Christian Hansen1, Elodie Angot1, Ann-Louise Bergström2, Jennifer A. Steiner1, Laura Pieri3, Gesine Paul1, Tiago F. Outeiro4,5, Ronald Melki3, Pekka Kallunki2, Karina Fog2, Jia-Yi Li1 and Patrik Brundin1 http://www.jci.org/articles/view/43366 Post Comment Private Reply Ignore Thread
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