Artículo
Lessons learned from protein aggregation: toward technological and biomedical applications
Avila, Cesar Luis
; Chaves, Analia Silvina
; Socias, Sergio Benjamin
; Vera Pingitore, Esteban
; González Lizarraga, Maria Florencia
; Vera, Claudia Cecilia
; Ploper, Diego
; Chehin, Rosana Nieves
Fecha de publicación:
10/2017
Editorial:
Springer Verlag Berlín
Revista:
Biophysical Reviews
ISSN:
1867-2450
e-ISSN:
1867-2469
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The close relationship between protein aggregation and neurodegenerative diseases has been the driving force behind the renewed interest in a field where biophysics, neurobiology and nanotechnology converge in the study of the aggregate state. On one hand, knowledge of the molecular principles that govern the processes of protein aggregation has a direct impact on the design of new drugs for high-incidence pathologies that currently can only be treated palliatively. On the other hand, exploiting the benefits of protein aggregation in the design of new nanomaterials could have a strong impact on biotechnology. Here we review the contributions of our research group on novel neuroprotective strategies developed using a purely biophysical approach. First, we examine how doxycycline, a well-known and innocuous antibiotic, can reshape α-synuclein oligomers into non-toxic high-molecular-weight species with decreased ability to destabilize biological membranes, affect cell viability and form additional toxic species. This mechanism can be exploited to diminish the toxicity of α-synuclein oligomers in Parkinson’s disease. Second, we discuss a novel function in proteostasis for extracellular glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in combination with a specific glycosaminoglycan (GAG) present in the extracellular matrix. GAPDH, by changing its quaternary structure from a tetramer to protofibrillar assembly, can kidnap toxic species of α-synuclein, and thereby interfere with the spreading of the disease. Finally, we review a brighter side of protein aggregation, that of exploiting the physicochemical advantages of amyloid aggregates as nanomaterials. For this, we designed a new generation of insoluble biocatalysts based on the binding of photo-immobilized enzymes onto hybrid protein:GAG amyloid nanofibrils. These new nanomaterials can be easily functionalized by attaching different enzymes through dityrosine covalent bonds.
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Articulos(INSIBIO)
Articulos de INST.SUP.DE INVEST.BIOLOGICAS
Articulos de INST.SUP.DE INVEST.BIOLOGICAS
Citación
Avila, Cesar Luis; Chaves, Analia Silvina; Socias, Sergio Benjamin; Vera Pingitore, Esteban; González Lizarraga, Maria Florencia; et al.; Lessons learned from protein aggregation: toward technological and biomedical applications; Springer Verlag Berlín; Biophysical Reviews; 9; 5; 10-2017; 501-515
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