Chemogenomics Systems Pharmacology Mapping of Potential Drug Targets for Treatment of Traumatic Brain Injury

Journal of Neurotrauma
Lirong WangXiang-Qun Sean Xie

Abstract

Traumatic brain injury (TBI) is associated with high mortality and morbidity. Though the death rate of initial trauma has dramatically decreased, no drug has been developed to effectively limit the progression of the secondary injury caused by TBI. TBI appears to be a predisposing risk factor for Alzheimer's disease (AD), whereas the molecular mechanisms remain unknown. In this study, we have conducted a research investigation of computational chemogenomics systems pharmacology (CSP) to identify potential drug targets for TBI treatment. TBI-induced transcriptional profiles were compared with those induced by genetic or chemical perturbations, including drugs in clinical trials for TBI treatment. The protein-protein interaction network of these predicted targets were then generated for further analyses. Some protein targets when perturbed, exhibit inverse transcriptional profiles in comparison with the profiles induced by TBI, and they were recognized as potential therapeutic targets for TBI. Drugs acting on these targets are predicted to have the potential for TBI treatment if they can reverse the TBI-induced transcriptional profiles that lead to secondary injury. In particular, our results indicated that TRPV4, NEUROD1, and HP...Continue Reading

References

Mar 1, 1990·Pharmacology, Biochemistry, and Behavior·M G Boyeson, D M Feeney
Mar 1, 1985·American Journal of Epidemiology·L R FrenchB Christians
May 1, 1997·Journal of Neurosurgery·D F KellyD A Hovda
May 5, 2000·The Cochrane Database of Systematic Reviews·I Roberts
May 5, 2000·The Cochrane Database of Systematic Reviews·G Schierhout, I Roberts
Jun 14, 2003·The Cochrane Database of Systematic Reviews·I RobertsA Wakai
Dec 19, 2003·Nucleic Acids Research·M A HarrisUNKNOWN Gene Ontology Consortium
Oct 12, 2004·Experimental Neurology·Milos D IkonomovicSteven T DeKosky
Dec 22, 2004·Progress in Neuro-psychopharmacology & Biological Psychiatry·Olli Tenovuo
Sep 14, 2006·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hidenori EndoPak H Chan
Oct 3, 2006·Annals of Emergency Medicine·David W WrightDonald G Stein
Dec 23, 2006·Nature Reviews. Cancer·Justin Lamb
Apr 19, 2007·Neurological Research·Sarah B RockswoldArchie Defillo
May 9, 2007·Nature Medicine·Rishi RakhitAvijit Chakrabartty
Jul 10, 2007·Progress in Brain Research·Corinna Van Den HeuvelRobert Vink
Jul 12, 2007·Pediatric Research·Robert W HickeySteven H Graham
Jan 23, 2008·Journal of Neurochemistry·Yuanbin LiuDavid Schubert
Apr 23, 2008·CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne·Eugene ParkAndrew J Baker
Dec 17, 2008·Molecular and Cellular Neurosciences·Sonia CanteriniMaria Teresa Fiorenza
Feb 5, 2010·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Ananda P Sen, Anil Gulati
Aug 31, 2010·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Seth I Berger, Ravi Iyengar
Oct 12, 2010·PloS One·Ilya KupershmidtMostafa Ronaghi
Dec 18, 2010·Nature Reviews. Genetics·Albert-László BarabásiJoseph Loscalzo
Apr 9, 2011·Antioxidants & Redox Signaling·Tohru Fukai, Masuko Ushio-Fukai
May 7, 2011·Bioinformatics·Arthur LiberzonJill P Mesirov
Nov 5, 2011·Physical Medicine and Rehabilitation Clinics of North America·Daniel H DaneshvarRobert C Cantu
Feb 7, 2012·Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine·Samir H Haddad, Yaseen M Arabi
Mar 7, 2012·Neuroscience and Biobehavioral Reviews·Thamil Mani Sivanandam, Mahendra Kumar Thakur
Jun 26, 2012·Brain, Behavior, and Immunity·Alok Kumar, David J Loane
Aug 18, 2012·Drug Discovery Today·Francesco IorioJulio Saez-Rodriguez
Jan 29, 2013·British Journal of Anaesthesia·A P Georgiou, A R Manara
Mar 21, 2013·Journal of Neurotrauma·Jacob D FealaJaques Reifman

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE58485

Methods Mentioned

BETA
gene mutation

Clinical Trials Mentioned

NCT00822900
NCT01730443
NCT00645190
NCT01734395

Software Mentioned

CVDPlatform
StemCellCKB
ChEMBL
Pharmaco Atlas Atlas
AlzPlatform
Illumina BaseSpace
STRING
BaseSpace

Related Concepts

Related Feeds

Alzheimer's Disease: APOE

Apolipoprotein E (APOE) polymorphic alleles are major genetic risk factors for Alzheimer's disease. Discover the latest research on APOE and other genetic determinants of Alzheimer's disease here.

Alzheimer's Disease: Transcription

Impaired transcription is associated with the pathogenesis and progression of conditions such as Alzheimer's disease (AD). Here are the latest discoveries pertaining to transcription and AD.

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.

Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Tau & TDP-43

Alzheimer's disease is a neurodegenerative disease. This feed focuses on the underlying role of tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.