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Altered Alpha-Synuclein, Parkin, and Synphilin Isoform Levels in Multiple System Atrophy Brains

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  1. Functional interaction between Lypd6 and nicotinic acetylcholine receptors

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Together with Parkinson's disease (PD) and dementia with Lewy bodies (DLB), Multiple System Atrophy (MSA) is a member of a diverse group of neurodegenerative disorders termed α-synucleinopathies. Previously, it has been shown that alpha-synuclein, parkin and synphilin-1 display disease specific transcription patterns in frontal cortex in PD, DLB and MSA, and thus may mediate the development of α-synucleinopathies. In this study, the differential expression of alpha-synuclein isoforms on transcriptional and translational levels was ascertained in MSA patients in comparison with PD cases and normal controls using isoform-specific primers and exon specific antibodies in substantia nigra, striatum, cerebellar cortex, and nucleus dentatus. These regions are severely affected by alpha-synuclein pathology and neurodegeneration. Further, we have also investigated transcript levels for parkin and synphilin-1 isoforms. In MSA brains, alpha-synuclein140 and alpha-synuclein112 isoform levels were significantly increased, whereas levels of the alpha-synuclein126 isoform were decreased in the substantia nigra, striatum, cerebellar cortex, and nucleus dentatus vs.

CONTROLS: Moreover, in MSA cases, we showed increased levels of parkin isoforms lacking the N-terminal ubiquitin-like domain and an aggregation-prone synphiln-1A isoform that causes neuronal toxicity in MSA. In PD brains, Parkin transcript variant 3, 7 and 11 were significantly and specifically overexpressed in the striatum and cerebellar cortex, together with synphilin-1A and 1C. The changes of isoform expression profiles in neurodegenerative diseases suggest alterations in the regulation of transcription and/or splicing events, leading to regional/cellular events that may be important for the highly increased aggregation of alpha-synuclein in the brain. This article is protected by copyright. All rights reserved.

TidsskriftJournal of Neurochemistry
Udgave nummer1
Sider (fra-til)172-185
StatusUdgivet - 2016

ID: 45726749