Openly accessible

Transcriptional modulation of the hippo signaling pathway by drugs used to treat bipolar disorder and schizophrenia

Panizzutti, B, Bortolasci, Chiara, Randall, Briana, Kidnapillai, S, Connor, Timothy, Richardson, Mark, Truong, Thi Thuy Trang, Liu, Shih-Jung, Morris, G, Gray, Laura, Kim, Jee Hyun, Dean, Olivia, Berk, Michael and Walder, Ken 2021, Transcriptional modulation of the hippo signaling pathway by drugs used to treat bipolar disorder and schizophrenia, International Journal of Molecular Sciences, vol. 22, no. 13, pp. 1-16, doi: 10.3390/ijms22137164.

Attached Files
Name Description MIMEType Size Downloads

Title Transcriptional modulation of the hippo signaling pathway by drugs used to treat bipolar disorder and schizophrenia
Author(s) Panizzutti, B
Bortolasci, ChiaraORCID iD for Bortolasci, Chiara orcid.org/0000-0002-0794-6363
Randall, Briana
Kidnapillai, S
Connor, Timothy
Richardson, MarkORCID iD for Richardson, Mark orcid.org/0000-0002-1650-0064
Truong, Thi Thuy Trang
Liu, Shih-JungORCID iD for Liu, Shih-Jung orcid.org/0000-0002-7903-5796
Morris, GORCID iD for Morris, G orcid.org/0000-0002-1299-4300
Gray, LauraORCID iD for Gray, Laura orcid.org/0000-0002-2776-3935
Kim, Jee HyunORCID iD for Kim, Jee Hyun orcid.org/0000-0002-5554-6946
Dean, OliviaORCID iD for Dean, Olivia orcid.org/0000-0002-6758-4763
Berk, Michael
Walder, Ken
Journal name International Journal of Molecular Sciences
Volume number 22
Issue number 13
Article ID 7164
Start page 1
End page 16
Total pages 16
Publisher MDPI
Place of publication Basel, Switzerland
Publication date 2021-07-01
ISSN 1661-6596
1422-0067
Keyword(s) ANTIPSYCHOTIC-DRUGS
Biochemistry & Molecular Biology
bipolar disorder
Chemistry
Chemistry, Multidisciplinary
connectivity map
drug repurposing
Hippo pathway
INDUCTION
inflammation
INHIBITION
KAPPA-B ACTIVATION
KINASE
Life Sciences & Biomedicine
MECHANISMS
neuroscience
NF2/MERLIN
Physical Sciences
psychiatry
psychotropic drugs
schizophrenia
Science & Technology
SUPPRESSION
URSOLIC ACID
YAP
Summary Recent reports suggest a link between positive regulation of the Hippo pathway with bipolar disorder (BD), and the Hippo pathway is known to interact with multiple other signaling pathways previously associated with BD and other psychiatric disorders. In this study, neuronal-like NT2 cells were treated with amisulpride (10 µM), aripiprazole (0.1 µM), clozapine (10 µM), lamotrigine (50 µM), lithium (2.5 mM), quetiapine (50 µM), risperidone (0.1 µM), valproate (0.5 mM), or vehicle control for 24 h. Genome-wide mRNA expression was quantified and analyzed using gene set enrichment analysis (GSEA), with genes belonging to Hippo, Wnt, Notch, TGF- β, and Hedgehog retrieved from the KEGG database. Five of the eight drugs downregulated the genes of the Hippo pathway and modulated several genes involved in the interacting pathways. We speculate that the regulation of these genes, especially by aripiprazole, clozapine, and quetiapine, results in a reduction of MAPK and NFκB pro-inflammatory signaling through modulation of Hippo, Wnt, and TGF-β pathways. We also employed connectivity map analysis to identify compounds that act on these pathways in a similar manner to the known psychiatric drugs. Thirty-six compounds were identified. The presence of antidepressants and antipsychotics validates our approach and reveals possible new targets for drug repurposing.
Language eng
DOI 10.3390/ijms22137164
Field of Research 110999 Neurosciences not elsewhere classified
0399 Other Chemical Sciences
0604 Genetics
0699 Other Biological Sciences
Socio Economic Objective 920410 Mental Health
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30153302

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in TR Web of Science
Scopus Citation Count Cited 0 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 15 Abstract Views, 1 File Downloads  -  Detailed Statistics
Created: Tue, 13 Jul 2021, 14:05:45 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.