Lessons learned from protein aggregation: toward technological and biomedical applications
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REVIEW
Lessons learned from protein aggregation: toward technological and biomedical applications César L. Avila 1,2 & Silvina Chaves 1,2 & Sergio B. Socias 1,2 & Esteban Vera-Pingitore 1,2 & Florencia González-Lizárraga 1,2 & Cecilia Vera 1,2 & Diego Ploper 1,2 & Rosana Chehín 1,2
Received: 18 June 2017 / Accepted: 8 August 2017 # International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany 2017
Abstract 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 highincidence 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 highmolecular-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 This article is part of a Special Issue on ‘Latin America’ edited by Pietro Ciancaglini and Rosangela Itri. * Rosana Chehín [email protected] 1
Instituto Superior de Investigaciones Biológicas (INSIBIO), Centro Científico Tecnológico (CCT) Tucumán, CONICET–Universidad Nacional de Tucumán (CONICET-UNT), Crisóstomo Alvarez 722, Tucumán, Argentina
2
Instituto de Química Biológica Dr. Bernabé Bloj, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Chacabuco 461, Tucumán T4000ILI, Argentina
(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 photoimmobilized enzymes onto hybrid protein:GAG amyloid nanofibrils. These new nanomaterials can be easily functionalized by attaching different enzymes through dityrosine covalent bonds. Keywords Amyloid . Amyloid functionalization . Alzheimer’s disease . Parkinson’s disease . Protein aggregation . Cross-beta structure . Glycosamin
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