INVESTIGADORES
CHAVES Analia Silvina
artículos
Título:
Lessons learned from protein aggregation: toward technological and biomedical applications
Autor/es:
AVILA, CÉSAR L.; CHAVES, SILVINA; SOCIAS, SERGIO B.; VERA-PINGITORE, ESTEBAN; GONZÁLEZ-LIZÁRRAGA, FLORENCIA; VERA, CECILIA; PLOPER, DIEGO; CHEHÍN, ROSANA
Revista:
Biophysical Reviews
Editorial:
Springer International Publishing
Referencias:
Año: 2017
ISSN:
1867-2450
Resumen:
The close relationship between protein aggregation and neurodegenerative diseases has throttled renewed interest in this field where biophysics, neurobiology and nanotechnology converge to study the aggregate state. In fact, knowing the molecular bases that govern the processes of protein aggregation have a direct impact on the design of new drugs for high-incidence pathologies that only have palliative treatment. On the other hand, exploiting the benefits of protein aggregation in the design of new nanomaterials could have a strong impact in biotechnology. Here we review our contributions on novel neuroprotective strategies developed from 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 less 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 GAPDH in combination with specific glycosaminoglycan (GAG) of the extracellular matrix. By changing its quaternary structure from tetramer to protofibrillar assembly, GAPDH could kidnap toxic species of α-synuclein interfering with the spreading of the disease. Finally, we review a brighter side of protein aggregation, exploiting physicochemical advantages of amyloid aggregates as nanomaterials. For this, we designed a new generation of insoluble biocatalysts based on photo-immobilized enzymes onto hybrid protein:GAG amyloid nanofibrils. The new nanomaterial can be easily functionalized by attaching different enzymes through dityrosine covalent bonds.