{"id":5013,"date":"2022-07-25T06:50:41","date_gmt":"2022-07-25T11:50:41","guid":{"rendered":"https:\/\/irrf.org\/?p=5013"},"modified":"2022-07-29T09:51:12","modified_gmt":"2022-07-29T14:51:12","slug":"frontiers-in-aging-neuroscience","status":"publish","type":"post","link":"https:\/\/irrf.org\/frontiers-in-aging-neuroscience\/","title":{"rendered":"Frontiers in Aging Neuroscience"},"content":{"rendered":"
(30 June 2022)<\/p>\n
AUTHORS<\/strong>:\u00a0 <\/span>Daniela Intartaglia1<\/sup><\/span>, Giuliana Giamundo1,2<\/sup><\/span>, Federica Naso1<\/sup><\/span>, Edoardo Nusco1<\/sup><\/span>, Simona Di Giulio1<\/sup><\/span>, Francesco Giuseppe Salierno1<\/sup><\/span>, Elena Polishchuk1<\/sup><\/span>, and Ivan Conte<\/b>1,2<\/sup><\/b><\/span><\/p>\n 1<\/sup><\/span>Telethon Institute of Genetics and Medicine, Pozzuoli, Italy, 2<\/sup><\/span>Department of Biology, University of Naples Federico II, Naples, Italy<\/p>\n This study was conducted with IRRF funds \u2013 Ivan Conte, PhD, Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.\u00a0 <\/span>Department of Biology, University of Naples Federico II, Naples, Italy.<\/b><\/p>\n \u2018Autophagy is a critical metabolic process that acts as a major self-digestion and recycling pathway contributing to maintain cellular homeostasis.\u00a0 <\/span>An emerging field of research supports the therapeutic modulation of autophagy for treating human neurodegenerative disorders, in which toxic aggregates are accumulated in neurons.\u00a0 <\/span>Our previous study identified Ezrin protein as an inhibitor of autophagy and lysosomal functions in the retina; thus, in turn, identifying it as a potential pharmacological target for increasing retinal cell clearance to treat inherited retinal dystrophies in which misfolded proteins have accumulated.\u00a0 <\/span>This study aimed to verify the therapeutic inhibition of Ezrin to induce clearance of toxic aggregates in a mouse model for a dominant form of retinitis pigmentosa (i.e., RHOP23H\/+<\/sup><\/span>).\u00a0 <\/span>We found that daily inhibition of Ezrin significantly decreased the accumulation of misfolded RHOP23H<\/sup><\/span> aggregates.\u00a0 <\/span>Remarkably, induction of autophagy, by a drug-mediated pulsatile inhibition of Ezrin, promoted the lysosomal clearance of disease-linked RHOP23H<\/sup><\/span> aggregates.\u00a0 <\/span>This was accompanied with a reduction of endoplasmic reticulum (ER)-stress, robust decrease of photoreceptors\u2019 cell death, amelioration in both retinal morphology and function culminating in a better preservation of vision.\u00a0 <\/span>Our study opens new perspectives for a pulsatile pharmacological induction of autophagy as a mutation-independent therapy paving the way toward a more effective therapeutic strategy to treat these devastating retinal disorders due to an accumulation of intracellular toxic aggregates.\u2019<\/p>\n