Protective Effects of l- and d-Carnosine on α-Crystallin Amyloid Fibril Formation: Implications for Cataract Disease

Bruno Giuseppe Pignataro, Sebastiano Cataldo, Silvia Nicoletti, Francesco Attanasio, Anna Savarino, Salvatore Fisichella, Enrico Rizzarelli, Vincenzo Giuseppe Nicoletti

Risultato della ricerca: Article

47 Citazioni (Scopus)

Abstract

Mildly denaturing conditions induce bovine α-crystallin, the major structural lens protein, to self-assemble into fibrillar structures in vitro. The natural dipeptide l-carnosine has been shown to have potential protective and therapeutic significance in many diseases. Carnosine derivatives have been proposed as potent agents for ophthalmic therapies of senile cataracts and diabetic ocular complications. Here we report the inhibitory effect induced by the peptide (l- and d-enantiomeric form) on α-crystallin fibrillation and the almost complete restoration of the chaperone activity lost after denaturant and/or heat stress. Scanning force microscopy (SFM), thioflavin T, and a turbidimetry assay have been used to determine the morphology of α-crystallin aggregates in the presence and absence of carnosine. DSC and a near-UV CD assay evidenced that the structural precursors of amyloid fibrils are polypeptide chain segments that lack stable structural elements. Moreover, we have found a disassembling effect of carnosine on α-crystallin amyloid fibrils. Finally, we show the ability of carnosine to restore most of the lens transparency in organ-cultured rat lenses exposed to similar denaturing conditions that were used for the in vitro experiments.
Lingua originaleEnglish
pagine (da-a)6522-6531
Numero di pagine10
RivistaBiochemistry
Volume2009-05
Stato di pubblicazionePublished - 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry

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    Pignataro, B. G., Cataldo, S., Nicoletti, S., Attanasio, F., Savarino, A., Fisichella, S., Rizzarelli, E., & Nicoletti, V. G. (2009). Protective Effects of l- and d-Carnosine on α-Crystallin Amyloid Fibril Formation: Implications for Cataract Disease. Biochemistry, 2009-05, 6522-6531.