Umeå University's logo

umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Single injection of small-molecule amyloid accelerator results in cell death of nigral dopamine neurons in mice
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
Umeå University, Faculty of Science and Technology, Department of Chemistry.ORCID iD: 0000-0003-2523-1940
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Show others and affiliations
2015 (English)In: Parkinson's Disease, ISSN 2090-8083, E-ISSN 2042-0080, Vol. 1, article id 15024Article in journal (Refereed) Published
Abstract [en]

The assembly process of a-synuclein toward amyloid fibers is linked to neurodegeneration in Parkinson´s disease. In the present study, we capitalized on the in vitro discovery of a small-molecule accelerator of a-synuclein amyloid formation and assessed its effects when injected in brains of normal mice. An accelerator and an inhibitor of a-synuclein amyloid formation, as well as vehicle only, were injected into the striatum of normal mice and follwed by behavioral evaluation, immunohistochemistry, and metabolomics up to six months later. The effects of molecules injected into the substansia nigra of normal and a-synuclein knockout mice were also analyzed. When accelerator or inhibitor was injected into the brain of normal mice no acute compound toxicity was found. However, 6 months after single striatal injection of accelerator, mice sensorimotor functions were impaired, whereas mice injected with inhibitor had no dysfunctions. Injection of accelerator (but not inhibitor or vehicle) into the substantia nigra revealed singificant loss of tyrosine hydroxylase (TH)-positive neurons after 3 months. No loss of TH-positive neurons was found in a-synuclein knock-out mice injected with accelerator intor the substantia nigra. Metabolic serum profiles from accelerator-injected normal mice matched those of newly diagnosed Parkinson´s disease patients, whereas the profiles from inhibitor-injected normal mice matched controls. Single inoculation of a small-molecule amyloid accelerator may be a new approach for studies of early events during dopamine neurodegeneration in mice.

Place, publisher, year, edition, pages
2015. Vol. 1, article id 15024
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Neurosciences
Research subject
cell research
Identifiers
URN: urn:nbn:se:umu:diva-117116DOI: 10.1038/npjparkd.2015.24Scopus ID: 2-s2.0-84978034239OAI: oai:DiVA.org:umu-117116DiVA, id: diva2:905282
Available from: 2016-02-22 Created: 2016-02-22 Last updated: 2024-07-02Bibliographically approved

Open Access in DiVA

fulltext(1704 kB)444 downloads
File information
File name FULLTEXT01.pdfFile size 1704 kBChecksum SHA-512
e00932d8fabace6de3fe1f3e32e541b4ff250ed0b101b7ab52125bdeb741c7f265da106c29ec8707c96da0f550751fc5f1c5bff62989566b74f3a55364ace470
Type fulltextMimetype application/pdf

Other links

Publisher's full textScopus

Authority records

Chermenina, MariaChorell, ErikAntti, HenrikAlmqvist, FredrikStrömberg, IngridWittung-Stafshede, Pernilla

Search in DiVA

By author/editor
Chermenina, MariaChorell, ErikAntti, HenrikAlmqvist, FredrikStrömberg, IngridWittung-Stafshede, Pernilla
By organisation
Department of Integrative Medical Biology (IMB)Department of Chemistry
In the same journal
Parkinson's Disease
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)Neurosciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 444 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 1551 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf