Expression Of α-synuclein And Ubiquitin In Skin Of Patients With Multiple System Atrophy

Background Multiple system atrophy(MSA) is an adult-onset progressive neurodegenerative disorder of unknown etiology.It is characterized clinically by any combination of parkinsonian, autonomic, cerebellar or pyramidal symptoms, and pathologically by cell loss, gliosis and glial cytoplasmic inclusions(GCIs) in several brain and spinal cord structures. Cases of MSA were previously reported under the terms of striatonigral degeneration(SND), olivopontocerebellar atrophy(OPCA), Shy-Drager syndrome(SDS),and idiopathic orthostatic hypotension(OH). The term was simplified into two major clinical subtypes: MSA-P(SND) and MSA-C(OPCA),according to their predominant motor disorder—parkinsonism or cerebellar. In 1989, GCIs were first described in the brains of patients with MSA; they were not present in a large series of other neurodegenerative disorders. The abundant presence of GCIs in all clinical subtypes of MSA led to the recognition of SDS, SND and sporadic OPCA as one disease entity characterized by neuronal multisystem degeneration with unique oligodendroglial inclusion pathology. In the late nineties, a-synuclein(AS) immunostaining was recognized as a sensitive marker of inclusion pathology in MSA,and the disorder is now classified among the “synucleinopathies”along with Parkinson’s disease(PD) and dementia with Lewy bodies(DLB), etc. The GCIs are argyrophilic, sickle-shaped, oval or conical cytoplasmic aggregates, which stain for both polymorphized AS and Ub.The abnormal accumulation of a-synuclein in MSA has been reported to occur in five cellular sites, as GCIs in oligodendroglial cytoplasm,glial nuclear inclusions(GNIs) in oligodendroglial nuclei, neuronal cytoplasmic and neuronal nuclear inclusions(NCIs and NNIs) and in neurites. Using different AS antibodies, most of the AS molecules have been shown to be present in neuronal and glial inclusions. Double immunolabeling with antibodies toboth AS and Ub has convincingly demonstrated a more abundant and extensive staining pattern with the former antibody.Objective To study the function of ubiquitin proteasome system and α-synuclein in multiple system atrophy(MSA) patients by the skin biopsy,and to explore the role of ubiquitin proteasome system in the pathogenesis of MSA.Methods This study samples included 5 MSA patients and 8 normal controls. Skin biopsies were performed in the MSA patients.Immunohistochemistry and Western blot were used to detect the expression of ubiquitin(Ub) and α-synuclein.Results Compared with control group,the expression of α-synuclein and ubiquitin in the skin dermal layer of MSA were raised,and the difference was statistically significant(P < 0.05).Conclusion The expression of ubiquitin proteasome system was higher in the skin of MSA patients, and ubiquitin proteasome system may be involved in the pathogenesis of...