IDENTIFICATION OF NOVEL DRUG/LEAD MOLECULE FOR SCHIZOPHRENIA TARGETING RGS4 GENE THROUGH IN-SILICO ANALYSIS

PDF

Published: 2022-12-24

DOI: 10.56557/upjoz/2022/v43i243299

Page: 88-100


S. ANITHA KUMARI *

Department of Zoology, University College for Women, Koti, Hyderabad, India.

ANITA K. PATLOLLA

NIH-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, Jackson, MS, USA.

*Author to whom correspondence should be addressed.


Abstract

Schizophrenia is a neuropsychiatric disorder that is caused by many factors including changes in the chemistry of the brain, structure of the brain, and genetic factors. The neuropathology of the disorder has been identified morphologically and physiologically through a number of parameters from a reduction in brain size and abnormalities in the neurotransmitter network affecting the brain to changes in the molecular composition of specific cell populations in the brain. Over a long period of time, clinicians and researchers have identified schizophrenia as a complex neurological genetic disorder as a result of the functionality of several susceptible genes. Various scientists are of the opinion that there are about 20 candidate genes that cause schizophrenia. Several genes like Dysbindin, Neuregulin, DAAO, G72, PRODH, COMT, and RGS4 have been proven to be the risk factors for schizophrenia disease. RGS4 was identified as a target gene for schizophrenia. Hence the present study was taken up to identify a Novel Drug/Lead Molecule from 12 selected drugs based on a bioinformatics approach for schizophrenia targeting the RGS4 gene. The genomics and proteomics approach of the RGS4 gene was carried out for nucleotide and protein sequences and the protein was modeled using SPDBV with 80% accuracy. The potential active site amino acids were predicted using molecular cavities based on energy and surface area and the protein was targeted using the best active site amino acids. The protein-ligand interactions were also performed using the Argus Lab engine with flexible docking. The data of the present study reveals that ziprasidone is showing maximum inhibition of the RGS4 gene among the 12 drugs selected for screening. It is thus concluded that ziprasidone with the lowest free energy and high affinity is the best inhibitor for the schizophrenia protein and hence it can be suggested for the treatment of schizophrenia.

Keywords: Schizophrenia, RGS4, novel drug/lead molecule


How to Cite

KUMARI, S. A., & PATLOLLA, A. K. (2022). IDENTIFICATION OF NOVEL DRUG/LEAD MOLECULE FOR SCHIZOPHRENIA TARGETING RGS4 GENE THROUGH IN-SILICO ANALYSIS. UTTAR PRADESH JOURNAL OF ZOOLOGY, 43(24), 88–100. https://doi.org/10.56557/upjoz/2022/v43i243299

Downloads

Download data is not yet available.

References

Kneisl C, Trigoboff E. Contemporary psychiatric-Mental Health Nursing. 2nd Edition, London: Pearson Prentice Ltd. 2009;371.

American Psychiatric Association. Task force on DSM-IV Diagnostic and statistical manual of mental disorders: DSM-IV-TR. American Psychiatric Pub; 2000. ISDN 978 – 0 – 89042 – 025 – 6: 299.

Carson VB. Mental health nursing: The nurse – patient journey. W.B. Saunders; 2000. ISBN 978 – 0 – 7216 – 8053 – 8. 638.

Available:http:// books.google.com/ books?.id= QM5rAAAA MAAJ

Hirsch SR, Weinberger DR. Schizophrenia. Wiley – Blackwell; 2003. ISDN 978-0-632-06388-8. 21.

Available:http:// books. google.com/books? Id = x3fms V55rigC&Pg=PA21

Brunet–Gout E, Decety J. Social brain dysfunctions in schizophrenia: a review of neuroimaging studies. Psychiatry Res. 2006;148(2-3):75–92.

DOI:10.1016/J.Psychresns. 2006.05.001.

DOI:http://dx.doi.org/10.1016%2Fj.pscychresns.2006.05.001PMID.17088049.

Available:http://www.ncbi.nim.nih.gov/pubmed/17088049

Velligan DI, Alphs LD. Negative symptoms in schizophrenia. The importance of Identification and Treatment. Psychiatric Times. 2008;28(3).

Available:http://www.psychiatrictimes.com/schizophrenia/article/10168/1147581).

Smith T, Weston C, Lieberman J. Schizophrenia (maintenance and treatment). Am. Fam physician. 2010;82(4):338- 339 PMID 20704164.

Available:https://www.ncbi.nlm.nih.gov/pubmed 20704164

Van OSJ, KAPUR S. Schizophrenia. Lancet. 2009;374(9690):635-45.

Available:http://xa.yimg.com/kq/groups/19525360/611943554/name/schizophrenia. The lancet.pdf

DOI:10.1016/S0140-6736 (09) 60995 – 8

DOI:http:// dx. doi. org/10.1016%2FSO140-6736%2809%2960995-8)

PMID 19700006

Available:https://www.ncbi.nlm.nih.gov/pubmed/19700006

Lewis DA. Is there a neuropathology of schizophrenia? The Neuroscientist. 2000;6:208-218.

Pilowsky LS, Karwin FW, Murray RM. Schizophrenia: a neurodevelopmental perspective. Neuropsychopharmacology. 1993;9:83-91.

Weinberger DR. From neuropathology to neurodevelopment. Lancet. 1995;346:552-557.

Levinson DF, Lewis CM, Wise LH. 16 Contributing groups. Meta-analysis of genome scans for schizophrenia. Am. J. Med. Genet (Neuropsychiatric Genet). 2002;114:SL-2:697-890.

Harrison PJ, Owen MJ. Genes for schizophrenia? Recent findings and their pathophysiological implications. Lancet. 2003;361:417-419.

Brzustowicz LM, Hodgkinson KA, Chow EW, Honer WG, Bassett AS. Location of a major susceptibility locus for familial schizophrenia on chromosome 1q21-q22. Science. 2000;288:678- 682.

Stefanis Nc, Trikalinos TA, Avramopoulos D, Smyrnis N, Evdokimidis I, Ntzani EE, Hatzimanolis A, Ioannidis JP, Stefanis CN. Association of RGS4 variants with schizotypy and cognitive endophenotypes at the population level. Behavioral and Brain Functions. 2008;4:46.

DOI:10.1186/1744 – 9081-4-46.PMC 2572614 PMID 18834502.

Prasad KM, Almasy L, Gur RC, Gur RE, Pogue – Geile M, Chowdari KV, Talkowski ME, Nimgoankar VL. RGS4 polymorphisms associated with variability of cognitive performance in a Family – Based schizophrenia sample. Schizophrenia Bulletin. 2009;36(5):983-90.

DOI:10.1093/schbul/sbp002.PMC 2930339. PMID 19282471.

Dean B, Boer S, Gibbons A, Money T, Scarr E. Recent Advances in postmorterm pathology and neurochemistry in schizophrenia. Current Opinion in Psychiatry. 2009;22(2):154-60.

DOI:10.1097/YCO.obo13e328323d52e.PMID. 19553869.

Ding L, Hegde AN. Expression of RGS4 splice variants in dorsolateral prefrontal cortex of schizophrenic and bipolar disorder patients. Biological Psychiatry. 2008;65(6):541 – 545.

DOI: 10:1016j. biopsych. 10.026. PMID 19041089.

Chowdari KV, Mirncis K, Semwal P, Wood J, Lawrence E, Bhatia T, Deshpande SN, Theima BK, Ferrell RE, Middleton FA, Devlin B, Levitt P, Lewis DA, Nimgoankar VL. Association and linkage analyses of RGS4 polymorphisms in schizophrenia. Hum Mol. Genet. 2002;11(12):1373-1380.

Morris DW, Rodgers A, Mcghee KA, Schwaiger S, Paul S, John Q, David M, John L, Waddington Michael G, Corvin AP. Confirming RGS4 as a susceptibility gene for schizophrenia. Amer. J. Med. Genet. Part B. (Neuropsychiatric Genetics). 2004;125 B:50-53.

Gold SJ, Ni YG, Dohlman HG, Nestier EJ. Regulators of G-protein signaling (RGS) proteins. Region specific expression of nine subtypes in rat brain. J Neurosci. 1997;17:8024 – 8037.

De.Vries I, Zheng B, Fisher T, Elenko E, Farquhar MG. The regulator of G protein signaling family. Annu Rev. Pharmacol Toxicol. 2000;40:235-271.

Mimics K, Middleton FA, Stanwood GD, Lewis DA, Levitt P. Disease – specific changes in regulator of G-protein signaling 4(RGS4) expression in schizophrenia. Molecular Psychiatry. 2001;6:293-301.

Heinz Lullmann, Klaus Mohr. Pharmakologie und Toxikologie: Arzneimittelwirkungen verstehen. Medikamente ge zielt einsetzen; ein Lehrbuch fur studierende der Medizin, der pharmazie und der Biowissenschaffen, eine informationsquelle fur Arzte, Apotheker und Gesundheitspolitiker; 2006.

Available:https://books. google.com/books?id= 7ewS8QACIYEC&pg= PP1). Georg Thieme verlag. ISBN 978-3-13-368516-0. Retrieved May 13, 2012

Alan F, Schatzberg, Charles B, Nemeroff. Essentials of clinical psychopharmacology. American Psychiatric Pub. 2006. P. 297.

Available:https://books.google.com/books?.id=i5zrVD1PAwEC&pg=PA297

ISBN 978-1-58562-243-6. Retrieved May 13, 2012.

Stahl Chiara Mattei, Maria Paola Rapagnani. Ziprasidone hydrochloride: What role in the management of schizophrenia?; 2011.

Available:https://www. ncbi. nlm.nih. gov/pmc/articles/PMC3663608).Journal of central nervous system disease.3:1. PMC3663608

Available:https://www. ncbi. nlm.nih. gov / pmc / articles / PMC 3663608?

PMID 23861634

Available:https://www.ncbi.nlm.nih.gov/pubmed/23861634

DOI:10.4137/JCNSD.S4138

DOI:https://doi.org/10.4137%2FJCNSD.S4138

Sandson NB, Armstrong SC, Cozza KL. An overview of psychotropic drug-drug interactions”. Psychosomatics. 2005;46(5):464-494.

PMID 16145193

Available:https://www.ncbi.Nlm. gov/pubmed/16145193

DOI:10.1176/appi.psy.46.5.464

DOI:https://doi.org/10.1176%2Fappi.psy.46.5.464.

Nicolson SE, Nemeroff CB. Ziprasidone in the treatment of mania in bipolar disorder. Neuropsychiatr Dis. Treat. 2007;3(6):823-34.

Available:https://www.ncbi.nlm.nih.Gov/pmc/articles/PMC2656324

PMC 2656324.

Available:htpps://www.ncbi.nlm.nih.gov/pmc/articles/PMC 2656324?

PMID 19300617

Available:htpps://www.ncbi.nlm.nih.gov/pubmed/19300617