RESUMEN
Since the identification of vacuolar protein sorting (VPS) 35, as a causative molecule for familial Parkinson's disease (PD), retromer-mediated endosomal machinery has been a rising factor in the pathogenesis of the disease. The retromer complex cooperates with sorting nexin (SNX) dimer and DNAJC13, another causal molecule in PD, to transport cargoes from endosomes to the trans-Golgi network, and is also involved in mitochondrial dynamics and autophagy. Retromer dysfunction may induce neuronal death leading to PD via several biological cascades, including misfolded, insoluble α-synuclein (aS) accumulation and mitochondrial dysfunction; however, the detailed mechanisms remain poorly understood. In this study, we showed that the stagnation of retromer-mediated retrograde transport consistently occurs in different PD-mimetic conditions, i.e., overexpression of PD-linked mutant DNAJC13, excess aS induction, or toxin-induced mitochondrial dysfunction. Mechanistically, DNAJC13 was found to be involved in clathrin-dependent retromer transport as a functional modulator of SNX1 together with heat shock cognate 70 kDa protein (Hsc70), which was controlled by the binding and dissociation of DNAJC13 and SNX1 in an Hsc70 activity-dependent manner. In addition, excess amount of aS decreased the interaction between SNX1 and VPS35, the core component of retromer. Furthermore, R33, a pharmacological retromer chaperone, reduced insoluble aS and mitigated rotenone-induced neuronal apoptosis. These findings suggest that retrograde transport regulated by SNX1-retromer may be profoundly involved in the pathogenesis of PD and is a potential target for disease-modifying therapy for the disease.
RESUMEN
We herein report the case of a 14-year-old girl who had been experiencing chronic fatigue, febricula, and social withdrawal for 20 months. No notable abnormalities were identified during routine checkups at a general pediatric hospital; symptomatic treatments did not affect her condition. She was diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Based on the concepts of Japanese traditional medicine, she was administered shosaikoto-based treatment. After several weeks of treatment, all of the symptoms had been dramatically alleviated, consequently resolving the issue of non-attendance at school. Shosaikoto-based medication may be a therapeutic option for treating ME/CFS in patients presenting with chronic febricula.
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Medicamentos Herbarios Chinos/uso terapéutico , Síndrome de Fatiga Crónica/complicaciones , Síndrome de Fatiga Crónica/terapia , Fiebre/complicaciones , Adolescente , Femenino , Humanos , JapónRESUMEN
Objective Dementia is a major cause of disruption for a healthy life expectancy in Japan. It has been suggested that the number of teeth is a modifiable risk factor for cognitive impairment and dementia. We therefore examined the possible association between the cognitive function and the number of natural and artificial teeth in community-dwelling Japanese elderly individuals. Methods Among the participants in our prospective, community-based study, 210 elderly individuals (103 men and 107 women; 78.1±4.9 years; mean age±standard deviation) underwent both dental examinations and a Mini-Mental State Examination (MMSE), as well as various medical checkups, in 2016 and 2017. Results The number of natural teeth was significantly associated with an individual's MMSE score. The percentage of cognitively normal subjects (MMSE scores: 27-30) decreased significantly with a decrease in the number of natural teeth. Among the MMSE items, the calculation ability was significantly and independently associated with the number of natural teeth. Regression was calculated as the predicted score of MMSE =21+0.3× (years of schooling) +0.1× (number of natural teeth). Among individuals with 19 or fewer natural teeth, those who had a total of 20 teeth or more, including both natural and artificial teeth, had significantly higher MMSE scores than those who had 19 or fewer natural and artificial teeth combined. Conclusion The number of natural teeth was significantly associated with the cognitive function, especially the calculation ability, and the use of artificial teeth was associated with the preservation of the cognitive function in community-dwelling elderly individuals.
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Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Disfunción Cognitiva/etiología , Demencia/diagnóstico , Demencia/etiología , Pérdida de Diente/complicaciones , Anciano , Anciano de 80 o más Años , Cognición , Femenino , Humanos , Vida Independiente , Japón , Masculino , Pruebas de Estado Mental y Demencia , Estudios Prospectivos , Factores de RiesgoRESUMEN
A 74-year-old female patient, who was diagnosed with neurofibromatosis type 1 (NF1) at the age of 40, was admitted with complaints of flickering vision and gait disturbance for the last 2 years. On admission, neurological examination revealed mild bilateral hearing loss and ataxia in the limb and trunk. Laboratory tests revealed anti-hepatitis C virus (HCV) antibody positivity and elevated HCV RNA by real-time polymerase chain reaction. The cerebrospinal fluid examination revealed a slightly yellowish appearance with elevated total protein levels. Gradient echo T2*-weighted brain magnetic resonance imaging (MRI) demonstrated a rim of hypointense lesions surrounding the surface of the cerebellum, brainstem, frontal and temporal lobes, and thalamus, which was considered as hemosiderin depositions. From these MRI findings, she was diagnosed as having superficial siderosis of the central nervous system. Cerebral angiography revealed an aneurysm-like dilatation at the bifurcation of the right internal carotid-posterior communicating artery. (99m)Tc-ethyl cysteinate dimer single-photon emission computed tomography revealed hypoperfusion in the bilateral frontal and temporal lobes. Pelvic plain X-ray, pelvic computed tomography, and lumbosacral MRI revealed a sacral defect and an anterior sacral polycystic meningocele communicating with the spinal subarachnoid space. The patient's symptoms gradually worsened, and she died of septic shock because of pyelonephritis at the age of 77. An autopsy was performed; on pathological examination, we did not observe any findings associated with rupture of the aneurysm-like dilatation in the bifurcation of the right internal carotid-posterior communicating artery and cerebral amyloid angiopathy. Because duropathies-a new neurological disease concept-have been implicated as a cause of bleeding in the superficial siderosis, the anterior sacral polycystic meningocele, a type of duropathies, was presumed to be the most probable bleeding source of the superficial siderosis in this patient. Bleeding from the meningocele might result from the vulnerability of vessel walls in NF1.
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Encefalopatías/patología , Meningocele/complicaciones , Meningocele/patología , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/patología , Siderosis/etiología , Siderosis/patología , Anciano , Autopsia , Encefalopatías/diagnóstico por imagen , Encefalopatías/etiología , Portador Sano , Femenino , Hepacivirus , Humanos , Imagen por Resonancia Magnética , Meningocele/diagnóstico por imagen , Neurofibromatosis 1/diagnóstico por imagen , Región Sacrococcígea , Siderosis/diagnóstico por imagenRESUMEN
Poststroke patients with functional constipation, assessed by the Rome III criteria, from 6 hospitals were recruited in a study on the effects of the traditional Japanese medicine Daikenchuto (DKT) on constipation. Thirty-four patients (17 men and 17 women; mean age: 78.1 ± 11.6 years) were randomly assigned to 2 groups; all patients received conventional therapy for constipation, and patients in the DKT group received 15 g/day of DKT for 4 weeks. Constipation scoring system (CSS) points and the gas volume score (GVS) (the measure of the intestinal gas volume calculated from plain abdominal radiographs) were recorded before and after a 4-week observation period. The total score on the CSS improved significantly in the DKT group compared to the control (P < 0.01). In addition, scores for some CSS subcategories (frequency of bowel movements, feeling of incomplete evacuation, and need for enema/disimpaction) significantly improved in the DKT group (P < 0.01, P = 0.049, and P = 0.03, resp.). The GVS was also significantly reduced in the DKT group compared to the control (P = 0.03). DKT in addition to conventional therapy is effective in treating functional constipation in poststroke patients. This study was a randomized controlled trial and was registered in the UMIN Clinical Trial Registry (no. UMIN000007393).
RESUMEN
Four Huntington's disease (HD) patients were treated with traditional Chinese medicines Yi-Gan San (YGS) and Chaihu-Jia-Longgu-Muli Tan (CLMT) in a cross-over manner. Two patients took YGS for 8 weeks first, and after 4 weeks of washing out, they took CLMT for 8 weeks. Two other patients took these medicines in reverse order. All patients showed a decrease in the Unified Huntington's Disease Rating Scale-motor assessment (from 106.3 +/- 4.7 to 89.6 +/- 5.8 as mean +/- SD, P = 0.0004) by YGS treatment with no extrapiramidal symptoms or changes of cognition or ADL. Our study suggests a possibility of a new treatment for involuntary movements.
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Medicamentos Herbarios Chinos/uso terapéutico , Enfermedad de Huntington/genética , Medicina Tradicional China/métodos , Anciano , Estudios Cruzados , Femenino , Humanos , Persona de Mediana Edad , Proyectos PilotoRESUMEN
Familial occurrence of inclusion body myositis is extremely rare, and only a few cases in Western countries have been reported. In these reports, a strong association of this disease with DR3 (DRB1*0301/0302) and the efficacy of immunosuppressants suggested that an immune pathomechanism is involved in the disease. We, for the first time, report two Japanese sisters who suffered myopathy clinicopathologically similar to inclusion body myositis. One sister received corticosteroid and azathioprine and the therapy relieved dysphagia. Both of our patients had DR15(2)/4 (DRB1*1502/0405), suggesting a distinct genetic association with the disease in the Japanese population.