Excessive proteostasis contributes to pathology in fragile X syndrome

• Published in: Neuron (Cambridge, Mass.) Vol. 111; no. 4; pp. 508 - 525.e7
• Main Authors: Louros, Susana R., Seo, Sang S., Maio, Beatriz, Martinez-Gonzalez, Cristina, Gonzalez-Lozano, Miguel A., Muscas, Melania, Verity, Nick C., Wills, Jimi C., Li, Ka Wan, Nolan, Matthew F., Osterweil, Emily K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.02.2023
• Subjects: AGS; Animals; bortezomib; Bortezomib - metabolism; Bortezomib - therapeutic use; Disease Models, Animal; FMR1; fragile X; Fragile X Mental Retardation Protein - genetics; Fragile X Syndrome; inferior colliculus; Mice; Mice, Knockout; proteasome; Proteasome Endopeptidase Complex - metabolism; Proteasome Endopeptidase Complex - therapeutic use; Proteostasis; PSMB5; seizures; UPS; proteasome; PSMB5; FMR1; UPS; inferior colliculus; seizures; fragile X; proteostasis; bortezomib; AGS

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...