Sci. Aging Knowl. Environ., 21 September 2005
Vol. 2005, Issue 38, p. pe28
[DOI: 10.1126/sageke.2005.38.pe28]


Membrane Permeabilization: A Common Mechanism in Protein-Misfolding Diseases

Hilal A. Lashuel

The author is at the Integrative Biosciences Institute, Laboratory of Molecular Neurobiology and Neuroproteomics, École Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland. E-mail: hilal.lashuel{at}

Key Words: protein misfolding • neurodegenerative disease • amyloid pore hypothesis • protofibril • Alzheimer's disease • Parkinson's disease

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."

Citation: H. A. Lashuel, Membrane Permeabilization: A Common Mechanism in Protein-Misfolding Diseases. Sci. Aging Knowl. Environ. 2005 (38), pe28 (2005).

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