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Sökning: L773:0028 0836 OR L773:1476 4687 > Discriminating alph...

  • Shahnawaz, MohammadUniv Texas Houston, TX 77004 USA (författare)

Discriminating alpha-synuclein strains in Parkinsons disease and multiple system atrophy

  • Artikel/kapitelEngelska2020

Förlag, utgivningsår, omfång ...

  • 2020-02-05
  • NATURE PUBLISHING GROUP,2020
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:liu-163879
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-163879URI
  • https://doi.org/10.1038/s41586-020-1984-7DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding Agencies|Michael J. Fox Foundation for Parkinsons disease; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P01NS44233, U54NS065736, K23NS075141, R01 FD004789, R01 NS092625, R01AG055053, R01AG061069]; Department of DefenseUnited States Department of Defense; Swedish Research CouncilSwedish Research Council [2016-00748]; Mayo Funds; [RO1 NS094535]
  • Synucleinopathies are neurodegenerative diseases that are associated with the misfolding and aggregation of alpha-synuclein, including Parkinsons disease, dementia with Lewy bodies and multiple system atrophy(1). Clinically, it is challenging to differentiate Parkinsons disease and multiple system atrophy, especially at the early stages of disease(2). Aggregates of alpha-synuclein in distinct synucleinopathies have been proposed to represent different conformational strains of alpha-synuclein that can self-propagate and spread from cell to cell(3-6). Protein misfolding cyclic amplification (PMCA) is a technique that has previously been used to detect alpha-synuclein aggregates in samples of cerebrospinal fluid with high sensitivity and specificity(7,8). Here we show that the alpha-synuclein-PMCA assay can discriminate between samples of cerebrospinal fluid from patients diagnosed with Parkinsons disease and samples from patients with multiple system atrophy, with an overall sensitivity of 95.4%. We used a combination of biochemical, biophysical and biological methods to analyse the product of alpha-synuclein-PMCA, and found that the characteristics of the alpha-synuclein aggregates in the cerebrospinal fluid could be used to readily distinguish between Parkinsons disease and multiple system atrophy. We also found that the properties of aggregates that were amplified from the cerebrospinal fluid were similar to those of aggregates that were amplified from the brain. These findings suggest that alpha-synuclein aggregates that are associated with Parkinsons disease and multiple system atrophy correspond to different conformational strains of alpha-synuclein, which can be amplified and detected by alpha-synuclein-PMCA. Our results may help to improve our understanding of the mechanism of alpha-synuclein misfolding and the structures of the aggregates that are implicated in different synucleinopathies, and may also enable the development of a biochemical assay to discriminate between Parkinsons disease and multiple system atrophy. Protein misfolding cyclic amplification (PMCA) technology can discriminate between patients with Parkinsons disease and patients with multiple system atrophy on the basis of the characteristics of the alpha-synuclein aggregates in the cerebrospinal fluid.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Mukherjee, AbhisekUniv Texas Houston, TX 77004 USA (författare)
  • Pritzkow, SandraUniv Texas Houston, TX 77004 USA (författare)
  • Mendez, NicolasUniv Texas Houston, TX 77004 USA (författare)
  • Rabadia, PrakrutiUniv Texas Houston, TX 77004 USA (författare)
  • Liu, XianganUniv Texas Houston, TX USA (författare)
  • Hu, BoUniv Texas Houston, TX USA (författare)
  • Schmeichel, AnnMayo Clin, MN USA (författare)
  • Singer, WolfgangMayo Clin, MN USA (författare)
  • Wu, GangUniv Texas Houston, TX USA (författare)
  • Tsai, Ah-LimUniv Texas Houston, TX USA (författare)
  • Shirani, HamidLinköpings universitet,Kemi,Tekniska fakulteten(Swepub:liu)hamsh43 (författare)
  • Nilsson, PeterLinköpings universitet,Kemi,Tekniska fakulteten(Swepub:liu)petni61 (författare)
  • Low, Phillip A.Mayo Clin, MN USA (författare)
  • Soto, ClaudioUniv Texas Houston, TX 77004 USA (författare)
  • Univ Texas Houston, TX 77004 USAUniv Texas Houston, TX USA (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Nature: NATURE PUBLISHING GROUP578:7794, s. 273-2770028-08361476-4687

Internetlänk

Hitta via bibliotek

  • Nature (Sök värdpublikationen i LIBRIS)

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