Papp–Lantos inclusions and the pathogenesis of multiple system atrophy: an update

@article{Jellinger2010PappLantosIA,
  title={Papp–Lantos inclusions and the pathogenesis of multiple system atrophy: an update},
  author={Kurt A. Jellinger and Peter L. Lantos},
  journal={Acta Neuropathologica},
  year={2010},
  volume={119},
  pages={657-667}
}
Multiple systemic atrophy (MSA) is a progressive, adult-onset neurodegenerative disorder of undetermined aetiology characterized by a distinctive oligodendrogliopathy with argyrophilic glial cytoplasmic inclusions (GCIs) and selective neurodegeneration. [...] Key Result The association between polymorphisms at the SNCA gene locus and the risk for developing MSA also points to a primary role of αSyn in its pathogenesis, while in a MBP promoter-driven αSyn transgenic mouse model gliosis accompanied the…Expand
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Multiple system atrophy (MSA) is a progressive neurodegenerative disease clinically characterized by parkinsonism, cerebellar ataxia and autonomic dysfunction. The pathological hallmark of MSA is the
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  • 2014
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Histological core feature are glial cytoplasmic inclusions in all types of oligodendroglia that contain aggregates of misfolded α‐Synuclein (α‐Syn), which are suggested finally to lead to a system‐specific pattern of neurodegeneration.
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TLDR
Multidisciplinary research to elucidate the genetic and molecular background of the deleterious cycle of noxious processes to develop reliable diagnostic biomarkers and to deliver targets for effective treatment of this hitherto incurable disorder is urgently needed.
Models of multiple system atrophy.
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This chapter gives an overview of the atypical Parkinson's syndrome MSA and summarizes the currently available MSA animal models and their relevance for pre-clinical testing of disease-modifying therapies.
Glia and alpha-synuclein in neurodegeneration: A complex interaction
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This review will highlight AS-dependent alterations of glial function and their impact on neuronal vulnerability thereby providing a detailed summary on the multifaceted role of glia in ASP.
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TLDR
It is shown that the density of OPCs was increased in a white matter region of the MSA brain, which is also severely affected by GCIs and myelin degeneration, raising the possibility that O PCs could be available to repair disease‐associated damage in MSA, consistent with their biological function.
Potential clinical utility of multiple system atrophy biomarkers
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It is suggested that the combination of neuroimaging and fluid biomarkers may be more successful than using single markers to increase the accuracy of the clinical (differential) diagnosis of MSA.
Glial dysfunction in the pathogenesis of α-synucleinopathies: emerging concepts
TLDR
A critical analysis of the role of glia in α-synucleinopathies including putative mechanisms promoting a chronically diseased glial microenvironment which can lead to detrimental neuronal changes, including cell loss is provided.
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