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Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
Mecanismo de la interacción de la membrana y la ruptura por la α-sinucleína
Nicholas P Reynolds1, Alice Soragni, Michael Rabe
1Institute of Physical Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Journal of the American Chemical Society
|October 8, 2011
Resumen
La agregación de alfa-sinucleína en las membranas lipídicas, un proceso clave en la enfermedad de Parkinson, implica la extracción de lípidos y el agrupamiento alrededor de los agregados. Las formas mutantes como A53T y E57K causan más daño a la membrana que la alfa-sinucleína de tipo salvaje.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- La bioquímica es la bioquímica.
- Biología Estructural Biología estructural.
Sus antecedentes:
- La enfermedad de Parkinson es un trastorno neurodegenerativo vinculado a la agregación de alfa-sinucleína en cuerpos de Lewy.
- La agregación de alfa-sinucleína está influenciada por las membranas lipídicas, que también están dañadas por estos agregados.
Objetivo del estudio:
- Para observar directamente la agregación de alfa-sinucleína en las bicapas lipídicas soportadas.
- Investigar el mecanismo de agregación y el daño a la membrana causado por la alfa-sinucleína de tipo silvestre y mutante.
Principales métodos:
- Microscopía de fluorescencia de ángulo supercrítico microscopía de fluorescencia de ángulo supercrítico.
- La transferencia de energía de resonancia Förster (FRET)
Principales resultados:
- Observación directa de la polimerización de la alfa-sinucleína y la extracción de lípidos de las bicapas.
- Los mutantes A53T y E57K causaron daños significativos en la membrana en concentraciones submicromolares.
- La alfa-sinucleína de tipo salvaje mostró una disrupción de la membrana reducida en comparación con los mutantes.
Conclusiones:
- La agregación de alfa-sinucleína en las membranas lipídicas sigue un mecanismo conservado que implica la extracción de lípidos.
- Las formas mutantes de alfa-sinucleína exhiben un mayor potencial de daño a la membrana que las de tipo salvaje.
- Este mecanismo de daño a la membrana puede contribuir a la toxicidad celular de la enfermedad de Parkinson.
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