Conformational or misfolding diseases are a large class of devastating human disorders associated with protein misfolding and aggregation. Most conformational diseases are caused by a combination of genetic and environmental factors, suggesting that spontaneous events can destabilize the protein involved in the pathology or impair the clearance mechanisms of misfolded aggregates. Aging is one of the risk factors associated to these events, and the clinical relevance of conformational disorders is growing dramatically, as they begin to reach epidemic proportions due to increases in mean lifespan. Currently, there are no effective strategies to slow or prevent these diseases. Intrabodies are promising therapeutic agents for the treatment of misfolding diseases, because of their virtually infinite ability to specifically recognize the different conformations of a protein, including pathological isoforms, and because they can be tarqeted to the potential sites of aggregation (both intra- and extracellular sites). These molecules can work as neutralizing agents bgainst amyloidogenic proteins by preventing their aggregation, and/or as molecular shunters of intracellular traffic by rerouting the protein from its potential aggregation site. The fast-developing field of recombinant antibody technology provides intrabodies with enhanced binding specificity and stability, together with lower immunogenicity, for use in a clinical setting. This review provides an update on the applications of intrabodies in misfolding diseases, with particular emphasis on an evaluation of their multipie and feasible modes of action. © 2008 Bentham Science Publishers Ltd.

Cardinale, A., Biocca, S. (2008). Combating protein misfolding and aggregation by intracellular antibodies. CURRENT MOLECULAR MEDICINE, 8(1), 2-11 [10.2174/156652408783565595].

Combating protein misfolding and aggregation by intracellular antibodies

BIOCCA, SILVIA
2008-01-01

Abstract

Conformational or misfolding diseases are a large class of devastating human disorders associated with protein misfolding and aggregation. Most conformational diseases are caused by a combination of genetic and environmental factors, suggesting that spontaneous events can destabilize the protein involved in the pathology or impair the clearance mechanisms of misfolded aggregates. Aging is one of the risk factors associated to these events, and the clinical relevance of conformational disorders is growing dramatically, as they begin to reach epidemic proportions due to increases in mean lifespan. Currently, there are no effective strategies to slow or prevent these diseases. Intrabodies are promising therapeutic agents for the treatment of misfolding diseases, because of their virtually infinite ability to specifically recognize the different conformations of a protein, including pathological isoforms, and because they can be tarqeted to the potential sites of aggregation (both intra- and extracellular sites). These molecules can work as neutralizing agents bgainst amyloidogenic proteins by preventing their aggregation, and/or as molecular shunters of intracellular traffic by rerouting the protein from its potential aggregation site. The fast-developing field of recombinant antibody technology provides intrabodies with enhanced binding specificity and stability, together with lower immunogenicity, for use in a clinical setting. This review provides an update on the applications of intrabodies in misfolding diseases, with particular emphasis on an evaluation of their multipie and feasible modes of action. © 2008 Bentham Science Publishers Ltd.
2008
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA
English
Con Impact Factor ISI
Alzheimer; Huntington; Immunotherapy; Intrabodies; Intracellular antibodies; Misfolding diseases; Prion; scFv
Cardinale, A., Biocca, S. (2008). Combating protein misfolding and aggregation by intracellular antibodies. CURRENT MOLECULAR MEDICINE, 8(1), 2-11 [10.2174/156652408783565595].
Cardinale, A; Biocca, S
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/45785
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