title: Membrane permeabilization: a common mechanism in protein-misfolding diseases.
abstract: Protein aggregation--and, more specifically, amyloid fibril formation--has been implicated as a primary cause of neurodegeneration in Alzheimer's disease, Parkinson's disease, and related disorders, but the mechanism by which this process triggers neuronal death is unknown. Mounting evidence from in vitro studies, cell culture, and animal models of these diseases supports the hypothesis that a structural intermediate on the pathway to fibril formation, rather than amyloid fibrils themselves, may be the pathogenic species. Characterization of these intermediates in solution or upon interactions with membranes indicate that these intermediates form pores and suggests that neurons could be killed by unregulated membrane permeabilization caused by such "amyloid pores."
authors.affiliation: Integrative Biosciences Institute, Laboratory of Molecular Neurobiology and Neuroproteomics, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland. hilal.lashuel@epfl.ch
authors.forename: Hilal A
authors.initials: HA
authors.lastname: Lashuel
mesh_terms: D002463:Cell Membrane Permeability; D006801:Humans; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000503:physiopathology*; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000473:pathology; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011506:Proteins