Publications

Authors:

Lorenzetto, Erika; Ettorre, Michele; Pontelli, Valeria; BOLOMINI VITTORI, Matteo; Bolognin, Silvia; Zorzan, Simone; Laudanna, Carlo; Buffelli, Mario Rosario

Title:

Rac1 selective activation improves retina ganglion cell survival and regeneration

Year:

2013

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

Elettronico

Referee:

Sì

Name of journal:

PLoS ONE

ISSN of journal:

1932-6203

N° Volume:

8

Number or Folder:

5

Page numbers:

e64350-13 pages

Keyword:

Rac1; nerve regeneration; Rho GTPases; optic nerve crush

Short description of contents:

In adult mammals, after optic nerve injury, retinal ganglion cells (RGCs) do not regenerate their axons and most of them die by apoptosis within a few days. Recently, several strategies that activate neuronal intracellular pathways were proposed to prevent such degenerative processes. The rho-related small GTPase Rac1 is part of a complex, still not fully understood, intracellular signaling network, mediating in neurons many effects, including axon growth and cell survival. However, its role in neuronal survival and regeneration in vivo has not yet been properly investigated. To address this point we intravitreally injected selective cell-penetrating Rac1 mutants after optic nerve crush and studied the effect on RGC survival and axonal regeneration. We injected two well-characterized L61 constitutively active Tat-Rac1 fusion protein mutants, in which a second F37A or Y40C mutation confers selectivity in downstream signaling pathways. Results showed that, 15 days after crush, both mutants were able to improve survival and to prevent dendrite degeneration, while the one harboring the F37A mutation also improved axonal regeneration. The treatment with F37A mutant for one month did not improve the axonal elongation respect to 15 days. Furthermore, we found an increase of Pak1 T212 phosphorylation and ERK1/2 expression in RGCs after F37A treatment, whereas ERK1/2 was more activated in glial cells after Y40C administration. Our data suggest that the selective activation of distinct Rac1-dependent pathways could represent a therapeutic strategy to counteract neuronal degenerative processes in the retina.

Web page:

http://dx.doi.org/10.1371/journal.pone.0064350

Product ID:

77174

Handle IRIS:

11562/582351

Deposited On:

June 3, 2013

Last Modified:

November 14, 2022

Bibliographic citation:

Lorenzetto, Erika; Ettorre, Michele; Pontelli, Valeria; BOLOMINI VITTORI, Matteo; Bolognin, Silvia; Zorzan, Simone; Laudanna, Carlo; Buffelli, Mario Rosario, Rac1 selective activation improves retina ganglion cell survival and regeneration «PLoS ONE» , vol. 8 , n. 5 , 2013 , pp. e64350-13 pages

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo