Umeå universitets logga

umu.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Peripheral administration of SOD1 aggregates does not transmit pathogenic aggregation to the CNS of SOD1 transgenic mice
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.ORCID-id: 0000-0002-3787-7629
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.ORCID-id: 0000-0003-0094-5429
Visa övriga samt affilieringar
2021 (Engelska)Ingår i: Acta neuropathologica communications, E-ISSN 2051-5960, Vol. 9, nr 1, artikel-id 111Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The deposition of aggregated proteins is a common neuropathological denominator for neurodegenerative disorders. Experimental evidence suggests that disease propagation involves prion-like mechanisms that cause the spreading of template-directed aggregation of specific disease-associated proteins. In transgenic (Tg) mouse models of superoxide dismutase-1 (SOD1)-linked amyotrophic lateral sclerosis (ALS), inoculation of minute amounts of human SOD1 (hSOD1) aggregates into the spinal cord or peripheral nerves induces premature ALS-like disease and template-directed hSOD1 aggregation that spreads along the neuroaxis. This infectious nature of spreading pathogenic aggregates might have implications for the safety of laboratory and medical staff, recipients of donated blood or tissue, or possibly close relatives and caregivers. Here we investigate whether transmission of ALS-like disease is unique to the spinal cord and peripheral nerve inoculations or if hSOD1 aggregation might spread from the periphery into the central nervous system (CNS). We inoculated hSOD1 aggregate seeds into the peritoneal cavity, hindlimb skeletal muscle or spinal cord of adult Tg mice expressing mutant hSOD1. Although we used up to 8000 times higher dose—compared to the lowest dose transmitting disease in spinal cord inoculations—the peripheral inoculations did not transmit seeded aggregation to the CNS or premature ALS-like disease in hSOD1 Tg mice. Nor was any hSOD1 aggregation detected in the liver, kidney, skeletal muscle or sciatic nerve. To explore potential reasons for the lack of disease transmission, we examined the stability of hSOD1 aggregates and found them to be highly vulnerable to both proteases and detergent. Our findings suggest that exposed individuals and personnel handling samples from ALS patients are at low risk of any potential transmission of seeded hSOD1 aggregation.

Ort, förlag, år, upplaga, sidor
BioMed Central, 2021. Vol. 9, nr 1, artikel-id 111
Nyckelord [en]
Aggregate stability, ALS, Amyotrophic lateral sclerosis, Peripheral administration, Prion-like, Protein aggregation, SOD1, Superoxide dismutase 1
Nationell ämneskategori
Neurologi Neurovetenskaper
Identifikatorer
URN: urn:nbn:se:umu:diva-185894DOI: 10.1186/s40478-021-01211-9ISI: 000665853700001PubMedID: 34158126Scopus ID: 2-s2.0-85109055645OAI: oai:DiVA.org:umu-185894DiVA, id: diva2:1579877
Forskningsfinansiär
Hjärnfonden, 2015-0234Hjärnfonden, 2016-0303Hjärnfonden, 2018-0310Hjärnfonden, 2019-0320Hjärnfonden, 2020-0353Knut och Alice Wallenbergs Stiftelse, 2012.0091Knut och Alice Wallenbergs Stiftelse, 2014.0305Knut och Alice Wallenbergs Stiftelse, 2020.0232Tillgänglig från: 2021-07-12 Skapad: 2021-07-12 Senast uppdaterad: 2021-07-12Bibliografiskt granskad

Open Access i DiVA

fulltext(4031 kB)122 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 4031 kBChecksumma SHA-512
d7f8d17def136f83c1f631f18c8fb4bb292e1e2900c3f06ab0cf1587013009ec38606bd95d6a8d676fbcba15172c179846cf71435986b381e6bd1e0304143b01
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextPubMedScopus

Person

Keskin, IsilEkhtiari Bidhendi, ElahehMarklund, MatthewAndersen, Peter M.Brännström, ThomasMarklund, Stefan L.Nordström, Ulrika

Sök vidare i DiVA

Av författaren/redaktören
Keskin, IsilEkhtiari Bidhendi, ElahehMarklund, MatthewAndersen, Peter M.Brännström, ThomasMarklund, Stefan L.Nordström, Ulrika
Av organisationen
PatologiNeurovetenskaperKlinisk kemi
I samma tidskrift
Acta neuropathologica communications
NeurologiNeurovetenskaper

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 122 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 345 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf