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  • Rofo, FadiUppsala universitet,Institutionen för farmaci,Protein drug design (author)

Wide-Ranging Effects on the Brain Proteome in a Transgenic Mouse Model of Alzheimer's Disease Following Treatment with a Brain-Targeting Somatostatin Peptide

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-06-25
  • American Chemical Society (ACS),2021
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-452435
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-452435URI
  • https://doi.org/10.1021/acschemneuro.1c00303DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Alzheimer’s disease is the most common neurodegenerative disorder characterized by the pathological aggregation of amyloid-β (Aβ) peptide. A potential therapeutic intervention in Alzheimer’s disease is to enhance Aβ degradation by increasing the activity of Aβ-degrading enzymes, including neprilysin. The somatostatin (SST) peptide has been identified as an activator of neprilysin. Recently, we demonstrated the ability of a brain-penetrating SST peptide (SST-scFv8D3) to increase neprilysin activity and membrane-bound Aβ42 degradation in the hippocampus of mice overexpressing the Aβ-precursor protein with the Swedish mutation (APPswe). Using LC–MS, we further evaluated the anti-Alzheimer’s disease effects of SST-scFv8D3. Following a triple intravenous injection of SST-scFv8D3, the LC–MS analysis of the brain proteome revealed that the majority of downregulated proteins consisted of mitochondrial proteins regulating fatty acid oxidation, which are otherwise upregulated in APPswe mice compared to wild-type mice. Moreover, treatment with SST-scFv8D3 significantly increased hippocampal levels of synaptic proteins regulating cell membrane trafficking and neuronal development. Finally, hippocampal concentrations of growth-regulated α (KC/GRO) chemokine and degradation of neuropeptide-Y were elevated after SST-scFv8D3 treatment. In summary, our results demonstrate a multifaceted effect profile in regulating mitochondrial function and neurogenesis following treatment with SST-scFv8D3, further suggesting the development of Alzheimer’s disease therapies based on SST peptides.

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  • Sandbaumhüter, Friederike A.Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Medicinsk masspektrometri(Swepub:uu)frisa865 (author)
  • Chourlia, AikateriniUppsala universitet,Institutionen för farmaci,Protein drug design(Swepub:uu)choai550 (author)
  • Metzendorf, Nicole G.,1979-Uppsala universitet,Institutionen för farmaci,Protein drug design(Swepub:uu)nineu226 (author)
  • Morrison, Jamie I.Uppsala universitet,Institutionen för farmaci,Protein drug design(Swepub:uu)jammo886 (author)
  • Syvänen, StinaUppsala universitet,Geriatrik(Swepub:uu)stsyv838 (author)
  • Andrén, Per E.,Professor,1957-Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab,Medicinsk masspektrometri(Swepub:uu)perandre (author)
  • Jansson, Erik T.Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Medicinsk masspektrometri(Swepub:uu)erija780 (author)
  • Hultqvist, Greta,1980-Uppsala universitet,Institutionen för farmaci,Protein drug design(Swepub:uu)grhul102 (author)
  • Uppsala universitetInstitutionen för farmaci (creator_code:org_t)

Related titles

  • In:ACS Chemical Neuroscience: American Chemical Society (ACS)12:13, s. 2529-25411948-7193

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