Pubblicazioni

Autori:

Asteriti, Sabrina; Marino, Valerio; Avesani, Anna; Biasi, Amedeo; Dal Cortivo, Giuditta; Cangiano, Lorenzo; Dell'Orco, Daniele

Titolo:

Recombinant protein delivery enables modulation of the phototransduction cascade in mouse retina

Anno:

2023

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Formato:

Elettronico

Referee:

Sì

Nome rivista:

Cellular and Molecular Life Sciences

ISSN Rivista:

1420-682X

N° Volume:

80

Numero o Fascicolo:

371

Intervallo pagine:

1-21

Parole chiave:

Cone dystrophy; Cone-rod dystrophy; Inherited retinal dystrophy; Liposome; Protein delivery; Protein therapy

Breve descrizione dei contenuti:

Inherited retinal dystrophies are often associated with mutations in the genes involved in the phototransduction cascade in photoreceptors, a paradigmatic signaling pathway mediated by G protein-coupled receptors. Photoreceptor viability is strictly dependent on the levels of the second messengers cGMP and Ca2+. Here we explored the possibility of modulating the phototransduction cascade in mouse rods using direct or liposome-mediated administration of a recombinant protein crucial for regulating the interplay of the second messengers in photoreceptor outer segments. The effects of administration of the free and liposome-encapsulated human guanylate cyclase-activating protein 1 (GCAP1) were compared in biological systems of increasing complexity (in cyto, ex vivo, and in vivo). The analysis of protein biodistribution and the direct measurement of functional alteration in rod photoresponses show that the exogenous GCAP1 protein is fully incorporated into the mouse retina and photoreceptor outer segments. Furthermore, only in the presence of a point mutation associated with cone-rod dystrophy in humans p.(E111V), protein delivery induces a disease-like electrophysiological phenotype, consistent with constitutive activation of the retinal guanylate cyclase. Our study demonstrates that both direct and liposome-mediated protein delivery are powerful complementary tools for targeting signaling cascades in neuronal cells, which could be particularly important for the treatment of autosomal dominant genetic diseases.

Note:

Sabrina Asteriti and Valerio Marino have contributed equally to this work

Pagina Web:

https://doi.org/10.1007/s00018-023-05022-0

Id prodotto:

136392

Handle IRIS:

11562/1114907

ultima modifica:

29 novembre 2023

Citazione bibliografica:

Asteriti, Sabrina; Marino, Valerio; Avesani, Anna; Biasi, Amedeo; Dal Cortivo, Giuditta; Cangiano, Lorenzo; Dell'Orco, Daniele, Recombinant protein delivery enables modulation of the phototransduction cascade in mouse retina «Cellular and Molecular Life Sciences» , vol. 80 , n. 371 , 2023 , pp. 1-21

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