Search: id:"swepub:oai:DiVA.org:kth-309166" >
Reconditioning the ...
Reconditioning the Neurogenic Niche of Adult Non-human Primates by Antisense Oligonucleotide-Mediated Attenuation of TGFβ Signaling
-
Peters, S. (author)
-
Kuespert, S. (author)
-
Wirkert, E. (author)
-
show more...
-
Heydn, R. (author)
-
Jurek, B. (author)
-
Johannesen, S. (author)
-
Hsam, O. (author)
-
Korte, S. (author)
-
Ludwig, F. T. (author)
-
Mecklenburg, L. (author)
-
Mrowetz, H. (author)
-
Altendorfer, B. (author)
-
Poupardin, R. (author)
-
Petri, S. (author)
-
Thal, D. R. (author)
-
Hermann, A. (author)
-
Weishaupt, J. H. (author)
-
Weis, J. (author)
-
- Aksoylu, I. S. (author)
- Karolinska Institutet
-
- Lewandowski, Sebastian (author)
- Karolinska Institutet,KTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab
-
Aigner, L. (author)
-
Bruun, T. -H (author)
-
Bogdahn, U. (author)
-
show less...
-
(creator_code:org_t)
- 2021-04-15
- 2021
- English.
-
In: Neurotherapeutics. - : Springer Nature. - 1933-7213 .- 1878-7479. ; 18:3, s. 1963-1979
- Related links:
-
https://doi.org/10.1...
-
show more...
-
https://link.springe...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
http://kipublication...
-
show less...
Abstract
Subject headings
Close
- Adult neurogenesis is a target for brain rejuvenation as well as regeneration in aging and disease. Numerous approaches showed efficacy to elevate neurogenesis in rodents, yet translation into therapies has not been achieved. Here, we introduce a novel human TGFβ-RII (Transforming Growth Factor—Receptor Type II) specific LNA-antisense oligonucleotide (“locked nucleotide acid”—“NVP-13”), which reduces TGFβ-RII expression and downstream receptor signaling in human neuronal precursor cells (ReNcell CX® cells) in vitro. After we injected cynomolgus non-human primates repeatedly i.th. with NVP-13 in a preclinical regulatory 13-week GLP-toxicity program, we could specifically downregulate TGFβ-RII mRNA and protein in vivo. Subsequently, we observed a dose-dependent upregulation of the neurogenic niche activity within the hippocampus and subventricular zone: human neural progenitor cells showed significantly (up to threefold over control) enhanced differentiation and cell numbers. NVP-13 treatment modulated canonical and non-canonical TGFβ pathways, such as MAPK and PI3K, as well as key transcription factors and epigenetic factors involved in stem cell maintenance, such as MEF2A and pFoxO3. The latter are also dysregulated in clinical neurodegeneration, such as amyotrophic lateral sclerosis. Here, we provide for the first time in vitro and in vivo evidence for a novel translatable approach to treat neurodegenerative disorders by modulating neurogenesis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Peters, S.
-
Kuespert, S.
-
Wirkert, E.
-
Heydn, R.
-
Jurek, B.
-
Johannesen, S.
-
show more...
-
Hsam, O.
-
Korte, S.
-
Ludwig, F. T.
-
Mecklenburg, L.
-
Mrowetz, H.
-
Altendorfer, B.
-
Poupardin, R.
-
Petri, S.
-
Thal, D. R.
-
Hermann, A.
-
Weishaupt, J. H.
-
Weis, J.
-
Aksoylu, I. S.
-
Lewandowski, Seb ...
-
Aigner, L.
-
Bruun, T. -H
-
Bogdahn, U.
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Neurosciences
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Pharmacology and ...
- Articles in the publication
-
Neurotherapeutic ...
- By the university
-
Royal Institute of Technology
-
Karolinska Institutet