Differential Contribution of Calcium-Activated Proteases and ER-Stress in Three Mouse Models of Retinitis Pigmentosa Expressing P23H Mutant RHO.
Adv Exp Med Biol
; 1185: 311-316, 2019.
Article
em En
| MEDLINE
| ID: mdl-31884630
ABSTRACT
Autosomal dominant retinitis pigmentosa (adRP) is mainly caused by mutations responsible for rhodopsin (RHO) misfolding. Although it was previously proved that unfolded RHO is retained into the endoplasmatic reticulum (ER) eliciting ER-stress, consequent mechanisms underlying photoreceptor degeneration need to be further clarified. Several animal models of RHO mutants have been developed for this purpose and for development of neuroprotective treatments. Here, we compared two of the most used models of adRP, the P23H mutant RHO transgenic and knock-in mouse models, in order to define which are their limits and potentials. Although they were largely used, the differences on the activation of the cell death pathways occurring in these two models still remain to be fully characterized. We present data proving that activation of calpains is a mechanism of cell death shared by both models and that molecules targeting calpains are neuroprotective. Conversely, the role of ER-stress contribution to cell death appears to be divergent and remains controversial.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rodopsina
/
Calpaína
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Retinose Pigmentar
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Morte Celular
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Estresse do Retículo Endoplasmático
Limite:
Animals
Idioma:
En
Revista:
Adv Exp Med Biol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália