Sumoylation inhibits α-synuclein aggregation and toxicity

Sumoylation of α-synuclein decreases its rate of aggregation and its deleterious effects in vitro and in vivo

Altered Energy Homeostasis and Resistance to Diet-Induced Obesity in KRAP-Deficient Mice

Obesity and related metabolic disorders have become leading causes of adult morbidity and mortality. KRAP (Ki-ras-induced actin-interacting protein) is a cytoskeleton-associated protein and a ubiquitous protein among tissues, originally identified as a cancer-related molecule, however, its physiological roles remain unknown. Here we demonstrate that KRAP-deficient (KRAP−/−) mice show enhanced metabolic rate, decreased adiposity, improved glucose tolerance, hypoinsulinemia and hypoleptinemia. KRAP−/− mice are also protected against high-fat diet-induced obesity and insulin resistance despite of hyperphagia. Notably, glucose uptake in the brown adipose tissue (BAT) in KRAP−/− mice is enhanced in an insulin-independent manner, suggesting that BAT is involved in altered energy homeostasis in KRAP−/− mice, although UCP (Uncoupling protein) expressions are not altered. Of interest is the down-regulation of fatty acid metabolism-related molecules, including acetyl-CoA carboxylase (ACC)-1, ACC-2 and fatty acid synthase in the liver of KRAP−/− mice, which could in part account for the metabolic phenotype in KRAP−/− mice. Thus, KRAP is a novel regulator in whole-body energy homeostasis and may be a therapeutic target in obesity and related diseases

The AAA-ATPase VPS4 Regulates Extracellular Secretion and Lysosomal Targeting of α-Synuclein

Many neurodegenerative diseases share a common pathological feature: the deposition of amyloid-like fibrils composed of misfolded proteins. Emerging evidence suggests that these proteins may spread from cell-to-cell and encourage the propagation of neurodegeneration in a prion-like manner. Here, we demonstrated that α-synuclein (αSYN), a principal culprit for Lewy pathology in Parkinson's disease (PD), was present in endosomal compartments and detectably secreted into the extracellular milieu. Unlike prion protein, extracellular αSYN was mainly recovered in the supernatant fraction rather than in exosome-containing pellets from the neuronal culture medium and cerebrospinal fluid. Surprisingly, impaired biogenesis of multivesicular body (MVB), an organelle from which exosomes are derived, by dominant-negative mutant vacuolar protein sorting 4 (VPS4) not only interfered with lysosomal targeting of αSYN but facilitated αSYN secretion. The hypersecretion of αSYN in VPS4-defective cells was efficiently restored by the functional disruption of recycling endosome regulator Rab11a. Furthermore, both brainstem and cortical Lewy bodies in PD were found to be immunoreactive for VPS4. Thus, VPS4, a master regulator of MVB sorting, may serve as a determinant of lysosomal targeting or extracellular secretion of αSYN and thereby contribute to the intercellular propagation of Lewy pathology in PD

Development Plan Diabetes Centre

This project is an ooutgrowth of the cooperation between the directory general of the Higher Education (DGHE) and the Japan Society for the Promotion of Science (JSPS), implemented by Airlangga University School of Medicine – Dr. Soetomo Hospital Surabaya, in collaboration with other Institution ini Indonesia as well as in Japa

Microendoscopic Posterior Decompression for Treating Thoracic Myelopathy Caused by Ossification of the Ligamentum Flavum: Case Series

Background and Objectives: Ossification of the ligamentum flavum (OLF) is a relatively common cause of thoracic myelopathy. Surgical treatment is recommended for patients with myelopathy. Generally, open posterior decompression, with or without fusion, is selected to treat OLF. We performed minimally invasive posterior decompression using a microendoscope and investigated the efficacy of this approach in treating limited type of thoracic OLF. Materials and Methods: Microendoscopic posterior decompression was performed for 19 patients (15 men and four women) with thoracic OLF with myelopathy aged between 35 to 81 years (mean age, 61.9 years). Neurological examination and preoperative magnetic resonance imaging (MRI) and computed tomography (CT) were used to identify the location and morphology of OLF. The surgery was performed using a midline approach or a unilateral paramedian approach depending on whether the surgeon used a combination of a tubular retractor and endoscope. The numerical rating scale (NRS) and modified Japanese Orthopedic Association (mJOA) scores were compared pre- and postoperatively. Perioperative complications and the presence of other spine surgeries before and after thoracic OLF surgery were also investigated. Results: Four midline and 15 unilateral paramedian approaches were performed. The average operative time per level was 99 min, with minor blood loss. Nine patients had a history of cervical or lumbar spine surgery before or after thoracic spine surgery. The mean pre- and postoperative NRS scores were 6.6 and 5.3, respectively. The mean recovery rate as per the mJOA score was 33.1% (mean follow-up period, 17.8 months), the recovery rates were significantly different between patients who underwent thoracic spine surgery alone (50.5%) and patients who underwent additional spine surgeries (13.7%). Regarding adverse events, one patient experienced dural tear, another experienced postoperative hematoma, and one other underwent reoperation for adjacent thoracic stenosis. Conclusion: Microendoscopic posterior decompression was applicable in limited type of thoracic OLF surgery including beak-shaped type and multi vertebral levels. However, whole spine evaluation is important to avoid missing other combined stenoses that may affect outcomes