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Molecular basis of ...
Molecular basis of mood and cognitive adverse events elucidated via a combination of pharmacovigilance data mining and functional enrichment analysis
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- Andronis, Christos (författare)
- Biovista, 34 Rodopoleos St, Athens 16777, Greece
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- Silva, João Pedro (författare)
- Univ Porto, Fac Pharm, Dept Biol Sci, Lab Toxicol,UCIBIO,REQUIMTE, P-4050313 Porto, Portugal
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- Lekka, Eftychia (författare)
- Biovista, 34 Rodopoleos St, Athens 16777, Greece
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- Virvilis, Vassilis (författare)
- Biovista, 34 Rodopoleos St, Athens 16777, Greece
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- Carmo, Helena (författare)
- Univ Porto, Fac Pharm, Dept Biol Sci, Lab Toxicol,UCIBIO,REQUIMTE, P-4050313 Porto, Portugal
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- Bampali, Konstantina (författare)
- Med Univ Vienna, Dept Mol Neurosci, Spitalgasse 4, A-1090 Vienna, Austria
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- Ernst, Margot (författare)
- Med Univ Vienna, Dept Mol Neurosci, Spitalgasse 4, A-1090 Vienna, Austria
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- Hu, Yang, 1989- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Loryan, Irena, 1977- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Richard, Jacques (författare)
- Sanofi R&D, 371 Ave Prof Blayac, F-34000 Montpellier, France
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- Carvalho, Félix (författare)
- Univ Porto, Fac Pharm, Dept Biol Sci, Lab Toxicol,UCIBIO,REQUIMTE, P-4050313 Porto, Portugal
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- Savić, Miroslav M (författare)
- Univ Belgrade, Fac Pharm, Dept Pharmacol, Vojvode Stepe 450, Belgrade 11000, Serbia
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(creator_code:org_t)
- 2020-06-05
- 2020
- Engelska.
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Ingår i: Archives of Toxicology. - : Springer Nature. - 0340-5761 .- 1432-0738. ; 94:8, s. 2829-2845
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Drug-induced Mood- and Cognition-related adverse events (MCAEs) are often only detected during the clinical trial phases of drug development, or even after marketing, thus posing a major safety concern and a challenge for both pharmaceutical companies and clinicians. To fill some gaps in the understanding and elucidate potential biological mechanisms of action frequently associated with MCAEs, we present a unique workflow linking observational population data with the available knowledge at molecular, cellular, and psychopharmacology levels. It is based on statistical analysis of pharmacovigilance reports and subsequent signaling pathway analyses, followed by evidence-based expert manual curation of the outcomes. Our analysis: (a) ranked pharmaceuticals with high occurrence of such adverse events (AEs), based on disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database, and (b) identified 120 associated genes and common pathway nodes possibly underlying MCAEs. Nearly two-thirds of the identified genes were related to immune modulation, which supports the critical involvement of immune cells and their responses in the regulation of the central nervous system function. This finding also means that pharmaceuticals with a negligible central nervous system exposure may induce MCAEs through dysregulation of the peripheral immune system. Knowledge gained through this workflow unravels putative hallmark biological targets and mediators of drug-induced mood and cognitive disorders that need to be further assessed and validated in experimental models. Thereafter, they can be used to substantially improve in silico/in vitro/in vivo tools for predicting these adversities at a preclinical stage.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- Adverse outcome pathways
- Cross-talk analysis
- Neurotoxicity
- Pharmaceuticals’ safety
- Psychiatric/psychological adverse events
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Andronis, Christ ...
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Silva, João Pedr ...
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Lekka, Eftychia
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Virvilis, Vassil ...
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Carmo, Helena
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Bampali, Konstan ...
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visa fler...
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Ernst, Margot
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Hu, Yang, 1989-
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Loryan, Irena, 1 ...
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Richard, Jacques
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Carvalho, Félix
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Savić, Miroslav ...
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visa färre...
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Uppsala universitet