Lessons learned from protein aggregation: toward technological and biomedical applications.

Autor: Avila CL; Instituto Superior de Investigaciones Biológicas (INSIBIO), Centro Científico Tecnológico (CCT) Tucumán, CONICET-Universidad Nacional de Tucumán (CONICET-UNT), Crisóstomo Alvarez 722, Tucumán, Argentina.; Instituto de Química Biológica Dr. Bernabé Bloj, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Chacabuco 461, Tucumán, T4000ILI, Argentina., Chaves S; Instituto Superior de Investigaciones Biológicas (INSIBIO), Centro Científico Tecnológico (CCT) Tucumán, CONICET-Universidad Nacional de Tucumán (CONICET-UNT), Crisóstomo Alvarez 722, Tucumán, Argentina.; Instituto de Química Biológica Dr. Bernabé Bloj, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Chacabuco 461, Tucumán, T4000ILI, Argentina., Socias SB; Instituto Superior de Investigaciones Biológicas (INSIBIO), Centro Científico Tecnológico (CCT) Tucumán, CONICET-Universidad Nacional de Tucumán (CONICET-UNT), Crisóstomo Alvarez 722, Tucumán, Argentina.; Instituto de Química Biológica Dr. Bernabé Bloj, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Chacabuco 461, Tucumán, T4000ILI, Argentina., Vera-Pingitore E; Instituto Superior de Investigaciones Biológicas (INSIBIO), Centro Científico Tecnológico (CCT) Tucumán, CONICET-Universidad Nacional de Tucumán (CONICET-UNT), Crisóstomo Alvarez 722, Tucumán, Argentina.; Instituto de Química Biológica Dr. Bernabé Bloj, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Chacabuco 461, Tucumán, T4000ILI, Argentina., González-Lizárraga F; Instituto Superior de Investigaciones Biológicas (INSIBIO), Centro Científico Tecnológico (CCT) Tucumán, CONICET-Universidad Nacional de Tucumán (CONICET-UNT), Crisóstomo Alvarez 722, Tucumán, Argentina.; Instituto de Química Biológica Dr. Bernabé Bloj, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Chacabuco 461, Tucumán, T4000ILI, Argentina., Vera C; Instituto Superior de Investigaciones Biológicas (INSIBIO), Centro Científico Tecnológico (CCT) Tucumán, CONICET-Universidad Nacional de Tucumán (CONICET-UNT), Crisóstomo Alvarez 722, Tucumán, Argentina.; Instituto de Química Biológica Dr. Bernabé Bloj, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Chacabuco 461, Tucumán, T4000ILI, Argentina., Ploper D; Instituto Superior de Investigaciones Biológicas (INSIBIO), Centro Científico Tecnológico (CCT) Tucumán, CONICET-Universidad Nacional de Tucumán (CONICET-UNT), Crisóstomo Alvarez 722, Tucumán, Argentina.; Instituto de Química Biológica Dr. Bernabé Bloj, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Chacabuco 461, Tucumán, T4000ILI, Argentina., Chehín R; Instituto Superior de Investigaciones Biológicas (INSIBIO), Centro Científico Tecnológico (CCT) Tucumán, CONICET-Universidad Nacional de Tucumán (CONICET-UNT), Crisóstomo Alvarez 722, Tucumán, Argentina. rosana@fbqf.unt.edu.ar.; Instituto de Química Biológica Dr. Bernabé Bloj, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Chacabuco 461, Tucumán, T4000ILI, Argentina. rosana@fbqf.unt.edu.ar.
Jazyk: angličtina
Zdroj: Biophysical reviews [Biophys Rev] 2017 Oct; Vol. 9 (5), pp. 501-515. Date of Electronic Publication: 2017 Sep 13.
DOI: 10.1007/s12551-017-0317-z
Abstrakt: 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.
Databáze: MEDLINE
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