Protein aggregation and prionopathies.
Prion protein and prion-like proteins share a number of characteristics. From the molecular point of view, they are constitutive proteins that aggregate following conformational changes into insoluble particles. These particles escape the cellular clearance machinery and amplify by recruiting the soluble for of their constituting proteins. The resulting protein aggregates are responsible for a number of neurodegenerative diseases such as Creutzfeldt-Jacob, Alzheimer, Parkinson and Huntington diseases. In addition, there are increasing evidences supporting the inter-cellular trafficking of these aggregates, meaning that they are "transmissible" between cells. There are also evidences that brain homogenates from individuals developing Alzheimer and Parkinson diseases propagate the disease in recipient model animals in a manner similar to brain extracts of patients developing Creutzfeldt-Jacob's disease. Thus, the propagation of protein aggregates from cell to cell may be a generic phenomenon that contributes to the evolution of neurodegenerative diseases, which has important consequences on human health issues. Moreover, although the distribution of protein aggregates is characteristic for each disease, new evidences indicate the possibility of overlaps and crosstalk between the different disorders. Despite the increasing evidences that support prion or prion-like propagation of protein aggregates, there are many unanswered questions regarding the mechanisms of toxicity and this is a field of intensive research nowadays.
Biologie cellulaire de la synapse, institut de biologie de l'École normale supérieure (IBENS), Inserm U1024 - CNRS 8197, 46, rue d'Ulm, 75005 Paris, France. Electronic address: renner@biologie.ens.fr.
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Laboratoire d'enzymologie et biochimie structurales, CNRS UPR 3082, bâtiment 34, avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
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D000375:Aging; D000544:Alzheimer Disease / Q000517:prevention & control; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001343:Autophagy; D001704:Biopolymers; D017322:Clinical Trials, Phase II as Topic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004705:Endocytosis; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry / Q000473:pathology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000473:pathology; D058225:Plaque, Amyloid / Q000737:chemistry / Q000473:pathology; D011134:Polysaccharides / Q000627:therapeutic use; D017096:Prion Diseases / Q000378:metabolism* / Q000473:pathology / Q000662:veterinary; D011328:Prions / Q000737:chemistry; D066263:Protein Aggregation, Pathological / Q000378:metabolism* / Q000473:pathology; D011487:Protein Conformation; D012995:Solubility
D001704:Biopolymers; D009419:Nerve Tissue Proteins; D011134:Polysaccharides; D011328:Prions; C486237:alzhemed
Agrégation des protéines; Alpha-synucleinopathies; Alpha-synucléinopathies; Alzheimer; Amyotrophic lateral sclerosis; Huntington; Parkinson; Prion; Protein aggregation; Sclérose latérale amyotrophique; Tauopathies