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1.
Neuron ; 111(4): 508-525.e7, 2023 02 15.
Article in English | MEDLINE | ID: mdl-36495869

ABSTRACT

In fragile X syndrome (FX), the leading monogenic cause of autism, excessive neuronal protein synthesis is a core pathophysiology; however, an overall increase in protein expression is not observed. Here, we tested whether excessive protein synthesis drives a compensatory rise in protein degradation that is protective for FX mouse model (Fmr1-/y) neurons. Surprisingly, although we find a significant increase in protein degradation through ubiquitin proteasome system (UPS), this contributes to pathological changes. Normalizing proteasome activity with bortezomib corrects excessive hippocampal protein synthesis and hyperactivation of neurons in the inferior colliculus (IC) in response to auditory stimulation. Moreover, systemic administration of bortezomib significantly reduces the incidence and severity of audiogenic seizures (AGS) in the Fmr1-/y mouse, as does genetic reduction of proteasome, specifically in the IC. Together, these results identify excessive activation of the UPS pathway in Fmr1-/y neurons as a contributor to multiple phenotypes that can be targeted for therapeutic intervention.


Subject(s)
Fragile X Syndrome , Mice , Animals , Proteasome Endopeptidase Complex/metabolism , Proteasome Endopeptidase Complex/therapeutic use , Proteostasis , Bortezomib/metabolism , Bortezomib/therapeutic use , Fragile X Mental Retardation Protein/genetics , Disease Models, Animal , Mice, Knockout
2.
Buenos Aires; ago. 2000. ilus.(Gerenc. ambient., 7, 66).
Monography in Spanish | BINACIS | ID: biblio-1222287

ABSTRACT

Las practicas de conservacion y restauracion del patrimonio historico cultural de nuestro pais son relativamente recientes.En la nota se presentan los resultados y las conclusiones de investigaciones llevadas a cabo sobre esculturas en metal y piedra expuestas a la intemperie natural en ambientes urbanos,las que sufren el daño provocado por la accion de agentes meteoricos y por la presencia de contaminantes ambientales tipicos de las grandes ciudades


Subject(s)
Environmental Pollutants
3.
Gerencia Ambiental ; 7(66): 456-62,508-10, ago. 2000. Ilus
Article in Spanish | BINACIS | ID: bin-141636

ABSTRACT

Las practicas de conservacion y restauracion del patrimonio historico cultural de nuestro pais son relativamente recientes.En la nota se presentan los resultados y las conclusiones de investigaciones llevadas a cabo sobre esculturas en metal y piedra expuestas a la intemperie natural en ambientes urbanos,las que sufren el daño provocado por la accion de agentes meteoricos y por la presencia de contaminantes ambientales tipicos de las grandes ciudades


Subject(s)
Environmental Pollutants
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