Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

Objectives To evaluate the clinical features, treatment scheme and long-term outcomes of stage 1、2 childhood neuroblastoma (NB). Methods The retrospective study included 49 newly diagnosed NB stage 1、2 patients from June 1998 to December 2010. Clinical data and long-term outcomes were analyzed. Results Twenty-four patients with stage 1 NB and twenty patients with stage 2 NB were found among all 237 patients with NB enrolled in this study. The median age at diagnosis was 25 months( 2 week to 9 year old),29 males and 20 females. Thirty-one patients (63.6%) without symptoms were discovered with tumor by physical or imaging examination. Thorax and abdomen were the most common sites of primary tumor (21 and 22 cases, accounting for 42.9% and 44.9% of all patients, respectively). Forty (81.6%) NB patients had favorable pathology classification. One patient was of MYCN amplification status. Urine vanilla mandelic acid was normal in 32 (91.4%) patients, and serum lactate dehydrogenase was less than five times of the normal value in all patients. Ten NB patients were treated ac-cording to the low-risk protocol who received surgery alone.Thirty-nine patients were treated according to intermediate-risk protocol who received both surgery and chemotherapy. All the patients achieved very good partial remission (100%).The medi-an follow-up period was 60 months(22 months to148months). Nine patients were lost after a follow up of 3 months in medi-an. The 2-、3-、5-year event free survival and overall survial of all 49 patients was 100%. Conclusions The prognosis for neu-roblastoma of stage 1、2 in this study was with 100%survival, which provides opportunity for further reduction of dosage and/or duration of episodes in chemotherapy.