Novel Target Sites for Drug Screening: A Special Reference to Cancer, Rheumatoid Arthritis and Parkinson’s Disease

Page: [107 - 121] Pages: 15

  • * (Excluding Mailing and Handling)

Abstract

Background: The humans can be affected by more than 100 types of cancers in which about 22 % cancer death are caused by tobacco, 10% due to alcohol and obesity, 5-10 % by genetic defects and 20 % by infections. Rheumatoid arthritis, an autoimmune disorder, occurs mostly in middle age, affects 2.5 times more to females than males and till 2015, more than 24.5 Million people get affected from this disorder. The deaths due to rheumatoid arthritis were 28000 in 1990 and increased to 38000 in 2013. Parkinson’s disease, a neurodegenerative disorder of central nervous system affects about 6.2 million people in 2015 and responsible for approximately 117400 deaths worldwide. Parkinson’s disease occurs mainly over the age of 60 and males get more affected than females.

Methods: Bibliographic database has created by mendeley desktop software for available literature in peer reviewed research articles especially by titles and disease names as keywords with AND Boolean operator (title AND year or author AND year). The intervention and findings of quality papers were extracted by detailed study and a conceptual framework has developed.

Results: Total 121 research and review articles are cited in this review to produce high impact in literature for pathophysiology and receptors involved in all three diseases. Changes in enzyme action, prohibition of angiogenesis and inhibition of microtubule are the main areas where anticancer molecules may perform significant effect. The immune system is not a good target for rheumatic treatment due to many complications that occur in body but fibroblast, like synoviocytes, proteases which are responsible for cartilage destruction and osteoclast differentiation may be the beneficial targets for pharmacoactive molecules in the treatment of rheumatoid arthritis. In Parkinson’s disease, supply of dopamine to brain from outside results in brain dopamine synthesis decrement which increase drug dependency. The compounds which stimulate secretion, reuptake inhibitor and increment in dopaminergic neurons may be good targets.

Conclusion: Alteration of signal transduction by a drug is the goal of chemogenomics, a new branch formed by combination of chemistry and genomics. The proliferation, angiogenesis and apoptosis of cancer cells are regulated by cellular signaling of transcription factors, protein kinases, transmembrane receptors, extracellular ligands and some external factors like oncogenic mutations, ubiquitin-proteasome pathway with epigenetic changes. Traditional anticancer drugs either alter DNA synthesis or control cell division while new drugs retard tumor growth or induce apoptosis. The deterioration of dopaminergic neurons in substantia nigra results in Parkinson’s disease with mental confusion, cognitive dysfunction and sleep disorder. Rheumatoid arthritis is characterized by inflammation, autoimmunity, joint destruction, deformity and premature mortality and treated mainly by anti-inflammatory and antirheumatic drugs. This review provides a comprehensive summary of objects which may act as potential targets for many health disorders.

Keywords: Cancer, Parkinson's disease, rheumatoid arthritis, novel target, Signal transduction, dopaminergic neurons.

Graphical Abstract

[1]
Rang HP. Drug receptors and their function. Nature 1971; 231(5298): 91-6.
[http://dx.doi.org/10.1038/231091a0] [PMID: 4930103]
[2]
Rang HP. The receptor concept: pharmacology’s big idea. Br J Pharmacol 2006; 147(Suppl. 1): S9-S16.
[http://dx.doi.org/10.1038/sj.bjp.0706457] [PMID: 16402126]
[3]
Gashaw I, Ellinghaus P, Sommer A, Asadullah K. What makes a good drug target? Drug Discov Today 2011; 16(23-24): 1037-43.
[http://dx.doi.org/10.1016/j.drudis.2011.09.007] [PMID: 21945861]
[4]
Hamani C, Lozano AM. Physiology and pathophysiology of Parkinson’s disease. Ann N Y Acad Sci 2003; 991: 15-21.
[http://dx.doi.org/10.1111/j.1749-6632.2003.tb07459.x] [PMID: 12846970]
[5]
Christoph W, Carol SOM. General aspects of signal transduction and cancer therapy.Cancer Signaling: From molecular biology to targeted therapy. 1st. Wiley-VCH Verlag GmbH & Co. KGaA 1998; pp. 1-21.
[6]
Mills G, Peter H, Mark I, Joe G, Craig T. The molecular basis of cancer. 4th ed. Philadelphia: Elsevier Saunders 2014; pp. 19-34.
[7]
Winklhofer KF. The parkin protein as a therapeutic target in Parkinson’s disease. Expert Opin Ther Targets 2007; 11(12): 1543-52.
[http://dx.doi.org/10.1517/14728222.11.12.1543] [PMID: 18020977]
[8]
Sweeney SE, Firestein GS. Signal transduction in rheumatoid arthritis. Curr Opin Rheumatol 2004; 16(3): 231-7.
[http://dx.doi.org/10.1097/00002281-200405000-00011] [PMID: 15103250]
[9]
Malemud CJ. Intracellular signaling pathways in Rheumatoid Arthritis. J Clin Cell Immunol 2013; 4(4): 160.
[http://dx.doi.org/10.4172/2155-9899.1000160] [PMID: 24619558]
[10]
Wu X, Liu X, Koul S, Lee CY, Zhang Z, Halmos B. AXL kinase as a novel target for cancer therapy. Oncotarget 2014; 5(20): 9546-63.
[http://dx.doi.org/10.18632/oncotarget.2542] [PMID: 25337673]
[11]
Erinn B. Rankin and Amato J. Giaccia. The receptor tyrosine kinase AXL in cancer progression. Cancers (Basel) 2016; 8(11): 103.
[http://dx.doi.org/10.3390/cancers8110103]
[12]
Paccez JD, Vogelsang M, Parker MI, Zerbini LF. The receptor tyrosine kinase Axl in cancer: biological functions and therapeutic implications. Int J Cancer 2014; 134(5): 1024-33.
[http://dx.doi.org/10.1002/ijc.28246] [PMID: 23649974]
[13]
Myers SH, Brunton VG, Unciti-Broceta A. AXL Inhibitors in cancer: A medicinal chemistry perspective. J Med Chem 2016; 59(8): 3593-608.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01273] [PMID: 26555154]
[14]
Sandeep G, Bhasker S, Ranganath YS. 7(1) Phosphodiesterase as a novel target in cancer chemotherapy. The Internet Journal of Pharmacology 2008; 7(1).
[15]
Savai R, Pullamsetti SS, Banat GA, et al. Targeting cancer with phosphodiesterase inhibitors. Expert Opin Investig Drugs 2010; 19(1): 117-31.
[http://dx.doi.org/10.1517/13543780903485642] [PMID: 20001559]
[16]
Murphy G, Nagase H. Progress in matrix metalloproteinase research. Mol Aspects Med 2008; 29(5): 290-308.
[http://dx.doi.org/10.1016/j.mam.2008.05.002] [PMID: 18619669]
[17]
Kim H, Zhai G, Liu Z, et al. Extracelluar matrix metalloproteinase as a novel target for pancreatic cancer therapy. Anticancer Drugs 2011; 22(9): 864-74.
[http://dx.doi.org/10.1097/CAD.0b013e328349311e] [PMID: 21730821]
[18]
Stamenkovic I. Extracellular matrix remodelling: the role of matrix metalloproteinases. J Pathol 2003; 200(4): 448-64.
[http://dx.doi.org/10.1002/path.1400] [PMID: 12845612]
[19]
Jablonska-Trypuc A, Matejczyk M, Rosochacki S. Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J Enzyme Inhib Med Chem 2016; 31(sup1): 177-83.
[20]
Furfine ES, Leban JJ, Landavazo A, Moomaw JF, Casey PJ. Protein farnesyltransferase: kinetics of farnesyl pyrophosphate binding and product release. Biochemistry 1995; 34(20): 6857-62.
[http://dx.doi.org/10.1021/bi00020a032] [PMID: 7756316]
[21]
Johnston SR. Farnesyl transferase inhibitors: a novel targeted tnerapy for cancer. Lancet Oncol 2001; 2(1): 18-26.
[http://dx.doi.org/10.1016/S1470-2045(00)00191-1] [PMID: 11905614]
[22]
Head J, Johnston SR. New targets for therapy in breast cancer: farnesyltransferase inhibitors. Breast Cancer Res 2004; 6(6): 262-8.
[http://dx.doi.org/10.1186/bcr947] [PMID: 15535857]
[23]
Bence AK, Crooks PA. The mechanism of L-canavanine cytotoxicity: arginyl tRNA synthetase as a novel target for anticancer drug discovery. J Enzyme Inhib Med Chem 2003; 18(5): 383-94.
[http://dx.doi.org/10.1080/1475636031000152277] [PMID: 14692504]
[24]
Bernstein SH, Venkatesh S, Li M, et al. The mitochondrial ATP-dependent Lon protease: a novel target in lymphoma death mediated by the synthetic triterpenoid CDDO and its derivatives. Blood 2012; 119(14): 3321-9.
[http://dx.doi.org/10.1182/blood-2011-02-340075] [PMID: 22323447]
[25]
Quirós PM, Español Y, Acín-Pérez R, et al. ATP-dependent Lon protease controls tumor bioenergetics by reprogramming mitochondrial activity. Cell Rep 2014; 8(2): 542-56.
[http://dx.doi.org/10.1016/j.celrep.2014.06.018] [PMID: 25017063]
[26]
Zhang Z, Zhao C. Sphingosine-1-phosphate and rheumatoid arthritis: Pathological implications and potential therapeutic targets. Innovative Rheumatology 2013.
[http://dx.doi.org/10.5772/53308]
[27]
McInnes IB, Liew FY, Gracie JA. Interleukin-18: a therapeutic target in rheumatoid arthritis? Arthritis Res Ther 2005; 7(1): 38-41.
[http://dx.doi.org/10.1186/ar1497] [PMID: 15642152]
[28]
Dai SM, Shan ZZ, Xu H, Nishioka K. Cellular targets of interleukin-18 in rheumatoid arthritis. Ann Rheum Dis 2007; 66(11): 1411-8.
[http://dx.doi.org/10.1136/ard.2006.067793] [PMID: 17502360]
[29]
Maguire-Zeiss KA. α-Synuclein: a therapeutic target for Parkinson’s disease? Pharmacol Res 2008; 58(5-6): 271-80.
[http://dx.doi.org/10.1016/j.phrs.2008.09.006] [PMID: 18840530]
[30]
Stefanis L. α-Synuclein in Parkinson’s disease. Cold Spring Harb Perspect Med 2012; 2(2)a009399
[http://dx.doi.org/10.1101/cshperspect.a009399] [PMID: 22355802]
[31]
Luo GR, Chen S, Le WD. Are heat shock proteins therapeutic target for Parkinson’s disease? Int J Biol Sci 2006; 3(1): 20-6.
[PMID: 17200688]
[32]
Leclerc E, Sturchler E, Vetter SW. The S100B/RAGE Axis in Alzheimer’s Disease. Cardiovasc Psychiatry Neurol 2010.2010539581
[http://dx.doi.org/10.1155/2010/539581] [PMID: 20672051]
[33]
Sathe K, Maetzler W, Lang JD, et al. S100B is increased in Parkinson’s disease and ablation protects against MPTP-induced toxicity through the RAGE and TNF-α pathway. Brain 2012; 135(Pt 11): 3336-47.
[http://dx.doi.org/10.1093/brain/aws250] [PMID: 23169921]
[34]
Wirdefeldt K, Adami HO, Cole P, Trichopoulos D, Mandel J. Epidemiology and etiology of Parkinson’s disease: a review of the evidence. Eur J Epidemiol 2011; 26(Suppl. 1): S1-S58.
[http://dx.doi.org/10.1007/s10654-011-9581-6] [PMID: 21626386]
[35]
Schlesinger I, Schlesinger N. Uric acid in Parkinson’s disease. Mov Disord 2008; 23(12): 1653-7.
[http://dx.doi.org/10.1002/mds.22139] [PMID: 18618666]
[36]
Miklya I, Göltl P, Hafenscher F, Pencz N. [The role of parkin in Parkinson’s disease Neuropsychopharmacol Hung 2014; 16(2): 67-76.
[PMID: 24978049]
[37]
Decressac M, Björklund A. TFEB: Pathogenic role and therapeutic target in Parkinson disease. Autophagy 2013; 9(8): 1244-6.
[http://dx.doi.org/10.4161/auto.25044] [PMID: 23715007]
[38]
Sardiello M. Transcription factor EB: from master coordinator of lysosomal pathways to candidate therapeutic target in degenerative storage diseases. Ann N Y Acad Sci 2016; 1371(1): 3-14.
[http://dx.doi.org/10.1111/nyas.13131] [PMID: 27299292]
[39]
Konakova M, Huynh DP, Yong W, Pulst SM. Cellular distribution of torsin A and torsin B in normal human brain. Arch Neurol 2001; 58(6): 921-7.
[http://dx.doi.org/10.1001/archneur.58.6.921] [PMID: 11405807]
[40]
Zhu L, Millen L, Mendoza JL, Thomas PJ. A unique redox-sensing sensor II motif in TorsinA plays a critical role in nucleotide and partner binding. J Biol Chem 2010; 285(48): 37271-80.
[http://dx.doi.org/10.1074/jbc.M110.123471] [PMID: 20861018]
[41]
Glant TT, Mikecz K, Rauch TA. Epigenetics in the pathogenesis of rheumatoid arthritis. BMC Med 2014; 12(1): 35.
[http://dx.doi.org/10.1186/1741-7015-12-35] [PMID: 24568138]
[42]
Szénási T, Oláh J, Szabó A, et al. Challenging drug target for Parkinson’s disease: Pathological complex of the chameleon TPPP/p25 and alpha-synuclein proteins. Biochim Biophys Acta Mol Basis Dis 2017; 1863(1): 310-23.
[http://dx.doi.org/10.1016/j.bbadis.2016.09.017] [PMID: 27671864]
[43]
Woynarowski JM, Trevino AV, Rodriguez KA, Hardies SC, Benham CJ. AT-rich islands in genomic DNA as a novel target for AT-specific DNA-reactive antitumor drugs. J Biol Chem 2001; 276(44): 40555-66.
[http://dx.doi.org/10.1074/jbc.M103390200] [PMID: 11487576]
[44]
Woynarowski JM. AT islands - their nature and potential for anticancer strategies. Curr Cancer Drug Targets 2004; 4(2): 219-34.
[http://dx.doi.org/10.2174/1568009043481524] [PMID: 15032671]
[45]
Yang Y, Karakhanova S, Hartwig W, et al. Mitochondria and Mitochondrial ROS in Cancer: Novel targets for anticancer therapy. J Cell Physiol 2016; 231(12): 2570-81.
[http://dx.doi.org/10.1002/jcp.25349] [PMID: 26895995]
[46]
Nitiss JL. DNA topoisomerase II and its growing repertoire of biological functions. Nat Rev Cancer 2009; 9(5): 327-37.
[http://dx.doi.org/10.1038/nrc2608] [PMID: 19377505]
[47]
Imming P, Sinning C, Meyer A. Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov 2006; 5(10): 821-34.
[http://dx.doi.org/10.1038/nrd2132] [PMID: 17016423]
[48]
Agrawal P. Recent advances in anticancer drugs development: G-Quadruplex as new drug target. J Pharmacovigil 2015; 3(2): 2-3.
[http://dx.doi.org/10.4172/2329-6887.1000e134]
[49]
Kim MY, Vankayalapati H, Shin-Ya K, Wierzba K, Hurley LH. Telomestatin, a potent telomerase inhibitor that interacts quite specifically with the human telomeric intramolecular g-quadruplex. J Am Chem Soc 2002; 124(10): 2098-9.
[http://dx.doi.org/10.1021/ja017308q] [PMID: 11878947]
[50]
Almond JB, Cohen GM. The proteasome: a novel target for cancer chemotherapy. Leukemia 2002; 16(4): 433-43.
[http://dx.doi.org/10.1038/sj.leu.2402417] [PMID: 11960320]
[51]
Crawford LJ, Walker B, Irvine AE. Proteasome inhibitors in cancer therapy. J Cell Commun Signal 2011; 5(2): 101-10.
[http://dx.doi.org/10.1007/s12079-011-0121-7] [PMID: 21484190]
[52]
Chang SH, Hong SH, Jiang HL, et al. GOLGA2/GM130, cis-Golgi matrix protein, is a novel target of anticancer gene therapy. Mol Ther 2012; 20(11): 2052-63.
[http://dx.doi.org/10.1038/mt.2012.125] [PMID: 22735382]
[53]
Yoshimura SI, Nakamura N, Barr FA, et al. Direct targeting of cis-Golgi matrix proteins to the Golgi apparatus. J Cell Sci 2001; 114(Pt 22): 4105-15.
[PMID: 11739642]
[54]
Parker AL, Kavallaris M, McCarroll JA. Microtubules and their role in cellular stress in cancer. Front Oncol 2014; 4: 153.
[http://dx.doi.org/10.3389/fonc.2014.00153] [PMID: 24995158]
[55]
Pasquier E, Kavallaris M. Microtubules: a dynamic target in cancer therapy. IUBMB Life 2008; 60(3): 165-70.
[http://dx.doi.org/10.1002/iub.25] [PMID: 18380008]
[56]
Juarez M, Filer A, Buckley CD. Fibroblasts as therapeutic targets in rheumatoid arthritis and cancer. Swiss Med Wkly 2012; 142(142)w13529
[http://dx.doi.org/10.4414/smw.2012.13529] [PMID: 22367980]
[57]
Haworth O, Burman A, Parsonage G, Filer A, Salmon M, Buckley CD. Stromal cells as new therapeutic targets in rheumatoid arthritis. Therapy 2005; 2(1): 121-9.
[http://dx.doi.org/10.2217/14750708.2.1.121]
[58]
Kastrinaki MC, Papadaki HA. Mesenchymal stromal cells in rheumatoid arthritis: biological properties and clinical applications. Curr Stem Cell Res Ther 2009; 4(1): 61-9.
[http://dx.doi.org/10.2174/157488809787169084] [PMID: 19149631]
[59]
Kim KW, Kim HR. Macrophage migration inhibitory factor: a potential therapeutic target for rheumatoid arthritis. Korean J Intern Med (Korean Assoc Intern Med) 2016; 31(4): 634-42.
[http://dx.doi.org/10.3904/kjim.2016.098] [PMID: 27169879]
[60]
Leech M, Metz C, Hall P, et al. Macrophage migration inhibitory factor in rheumatoid arthritis: evidence of proinflammatory function and regulation by glucocorticoids. Arthritis Rheum 1999; 42(8): 1601-8.
[http://dx.doi.org/10.1002/1529-0131(199908)42:8<1601:AID-ANR6>3.0.CO;2-B] [PMID: 10446857]
[61]
Kobayashi Y, Okunishi H. Mast cells as a target of rheumatoid arthritis treatment. Jpn J Pharmacol 2002; 90(1): 7-11.
[http://dx.doi.org/10.1254/jjp.90.7] [PMID: 12396022]
[62]
Hegarty SV, Sullivan AM, O’Keeffe GW. The Epigenome as a therapeutic target for Parkinson’s disease. Neural Regen Res 2016; 11(11): 1735-8.
[http://dx.doi.org/10.4103/1673-5374.194803] [PMID: 28123403]
[63]
Park M, Keung AJ, Khalil AS. The epigenome: the next substrate for engineering. Genome Biol 2016; 17(1): 183.
[http://dx.doi.org/10.1186/s13059-016-1046-5] [PMID: 27582168]
[64]
Kelly TK, De Carvalho DD, Jones PA. Epigenetic modifications as therapeutic targets. Nat Biotechnol 2010; 28(10): 1069-78.
[http://dx.doi.org/10.1038/nbt.1678] [PMID: 20944599]
[65]
Luo Y, Hoffer A, Hoffer B, Qi X. Mitochondria: A therapeutic target for Parkinson’s disease? Int J Mol Sci 2015; 16(9): 20704-30.
[http://dx.doi.org/10.3390/ijms160920704] [PMID: 26340618]
[66]
Kumar S, Ahmad MK, Waseem M, Pandey AK. Drug Targets for cancer treatment: An overview. Med Chem 2015; 5: 115-23.
[67]
Vasudev NS, Reynolds AR. Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions. Angiogenesis 2014; 17(3): 471-94.
[http://dx.doi.org/10.1007/s10456-014-9420-y] [PMID: 24482243]
[68]
Stehn JR, Haass NK, Bonello T, et al. A novel class of anticancer compounds targets the actin cytoskeleton in tumor cells. Cancer Res 2013; 73(16): 5169-82.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-4501] [PMID: 23946473]
[69]
Shapiro GI, Harper JW. Anticancer drug targets: cell cycle and checkpoint control. J Clin Invest 1999; 104(12): 1645-53.
[http://dx.doi.org/10.1172/JCI9054] [PMID: 10606615]
[70]
Liu H, Pope RM. The role of apoptosis in rheumatoid arthritis. Curr Opin Pharmacol 2003; 3(3): 317-22.
[http://dx.doi.org/10.1016/S1471-4892(03)00037-7] [PMID: 12810199]
[71]
Méric JB, Rottey S, Olaussen K, et al. Cyclooxygenase-2 as a target for anticancer drug development. Crit Rev Oncol Hematol 2006; 59(1): 51-64.
[http://dx.doi.org/10.1016/j.critrevonc.2006.01.003] [PMID: 16531064]
[72]
Prashantha Kumar BR, Praveen TK, Nanjan MJ, Karveker MD, Suresh B. Some neuropharmacological actions of 3-methyl-5-phenyl-(4′-methyl) qulnolenodlazeplne. Int J Pharmacol 2012; 39(6): 2-9.
[73]
Garg R, Benedetti LG, Abera MB, Wang H, Abba M, Kazanietz MG. Protein kinase C and cancer: what we know and what we do not. Oncogene 2014; 33(45): 5225-37.
[http://dx.doi.org/10.1038/onc.2013.524] [PMID: 24336328]
[74]
Lacal JC. Choline kinase as a precision medicine target for therapy in cancer, autoimmune diseases and malaria. Precis Med 2015; 1: 1-12.
[75]
Mackay HJ, Twelves CJ. Protein kinase C: a target for anticancer drugs? Endocr Relat Cancer 2003; 10(3): 389-96.
[http://dx.doi.org/10.1677/erc.0.0100389] [PMID: 14503915]
[76]
Geahlen RL. Getting Syk: spleen tyrosine kinase as a therapeutic target. Trends Pharmacol Sci 2014; 35(8): 414-22.
[http://dx.doi.org/10.1016/j.tips.2014.05.007] [PMID: 24975478]
[77]
Norman P. Investigational Bruton’s tyrosine kinase inhibitors for the treatment of rheumatoid arthritis. Expert Opin Investig Drugs 2016; 25(8): 891-9.
[http://dx.doi.org/10.1080/13543784.2016.1182499] [PMID: 27148767]
[78]
Tandon VR, Mahajan A, Singh JB, Verma S, Alpha V. Beta 3 Integrin : A novel therapeutic target in Rheumatoid arthritis. JK Science. Journal of Medical Education & Research 2005; 7(2): 2-3.
[79]
Hisahara S, Shimohama S. Dopamine receptors and Parkinson’s disease. Int J Med Chem 2011.2011403039
[http://dx.doi.org/10.1155/2011/403039] [PMID: 25954517]
[80]
Simuni T, Surmeier DJ. Calcium channels as a potential target for neuroprotection in Parkinson’s disease. US Neurol 2011; 109-12.
[http://dx.doi.org/10.17925/USN.2011.07.02.109]
[81]
Leclerc E, Fritz G, Vetter SW, Heizmann CW. Binding of S100 proteins to RAGE: An update. Biochimica et Biophysica Acta (BBA) -. Molecular Cell Research 2009; 1793(6): 993-1007.
[82]
Calì T, Ottolini D, Brini M. Calcium signaling in Parkinson’s disease. Cell Tissue Res 2014; 357(2): 439-54.
[http://dx.doi.org/10.1007/s00441-014-1866-0] [PMID: 24781149]
[83]
Flinn LJ, Keatinge M, Bretaud S, et al. TigarB causes mitochondrial dysfunction and neuronal loss in PINK1 deficiency. Ann Neurol 2013; 74(6): 837-47.
[http://dx.doi.org/10.1002/ana.23999] [PMID: 24027110]
[84]
Anand VS, Braithwaite SP. LRRK2 in Parkinson’s disease: biochemical functions. FEBS J 2009; 276(22): 6428-35.
[http://dx.doi.org/10.1111/j.1742-4658.2009.07341.x] [PMID: 19804416]
[85]
Lee BD, Dawson VL, Dawson TM. Leucine-rich repeat kinase 2 (LRRK2) as a potential therapeutic target in Parkinson’s disease. Trends Pharmacol Sci 2012; 33(7): 365-73.
[http://dx.doi.org/10.1016/j.tips.2012.04.001] [PMID: 22578536]
[86]
Wakade C, Chong R. A novel treatment target for Parkinson’s disease. J Neurol Sci 2014; 347(1-2): 34-8.
[http://dx.doi.org/10.1016/j.jns.2014.10.024] [PMID: 25455298]
[87]
Chaturvedi RK, Beal MF. PPAR: a therapeutic target in Parkinson’s disease. J Neurochem 2008; 106(2): 506-18.
[http://dx.doi.org/10.1111/j.1471-4159.2008.05388.x] [PMID: 18384649]
[88]
Francardo V. Sigma-1 receptor: a potential new target for Parkinson’s disease? Neural Regen Res 2014; 9(21): 1882-3.
[http://dx.doi.org/10.4103/1673-5374.145351] [PMID: 25558236]
[89]
Nguyen L, Lucke-Wold BP, Mookerjee SA, et al. Role of sigma-1 receptors in neurodegenerative diseases. J Pharmacol Sci 2015; 127(1): 17-29.
[http://dx.doi.org/10.1016/j.jphs.2014.12.005] [PMID: 25704014]
[90]
Savai R, Pullamsetti SS, Banat GA, et al. Targeting cancer with phosphodiesterase inhibitors. Expert Opin Investig Drugs 2010; 19(1): 117-31.
[http://dx.doi.org/10.1517/13543780903485642] [PMID: 20001559]
[91]
Maximiano S, Magalhães P, Guerreiro MP, Morgado M. Trastuzumab in the Treatment of Breast Cancer. BioDrugs 2016; 30(2): 75-86.
[http://dx.doi.org/10.1007/s40259-016-0162-9] [PMID: 26892619]
[92]
Gibellini L, Pinti M, Bartolomeo R, et al. Inhibition of Lon protease by triterpenoids alters mitochondria and is associated to cell death in human cancer cells. Oncotarget 2015; 6(28): 25466-83.
[http://dx.doi.org/10.18632/oncotarget.4510] [PMID: 26314956]
[93]
Pernia Michele, Galvagniona Celine, Maltsevc Alexander, Meisla Georg, et al. A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity. PNAS 2017; 114: 12: E2543.
[http://dx.doi.org/10.1073/pnas.1610586114]
[94]
Luo G-R, Chen S, Le W-D. Are heat shock proteins therapeutic target for Parkinson’s disease? Int J Biol Sci 2006; 3(1): 20-6.
[PMID: 17200688]
[95]
Kim SJ, Ryu MJ, Han J, et al. Activation of the HMGB1-RAGE axis upregulates TH expression in dopaminergic neurons via JNK phosphorylation Biochem Biophys Res Commun 2017; 4: 493(1): 358-64.
[http://dx.doi.org/10.1016/j.bbrc.2017.09.017]
[96]
Bandopadhyay R, Kingsbury AE, Muqit MM, et al. Synphilin-1 and parkin show overlapping expression patterns in human brain and form aggresomes in response to proteasomal inhibition. Neurobiol Dis 2005; 20(2): 401-11.
[http://dx.doi.org/10.1016/j.nbd.2005.03.021] [PMID: 15894486]
[97]
Riederer P, Laux G. MAO-inhibitors in Parkinson’s Disease. Exp Neurobiol 2011; 20(1): 1-17.
[http://dx.doi.org/10.5607/en.2011.20.1.1] [PMID: 22110357]
[98]
Liu JS, Kuo SR, McHugh MM, Beerman TA, Melendy T. Adozelesin triggers DNA damage response pathways and arrests SV40 DNA replication through replication protein A inactivation. J Biol Chem 2000; 275(2): 1391-7.
[http://dx.doi.org/10.1074/jbc.275.2.1391] [PMID: 10625690]
[99]
Iwai M, Hara A, Andoh T, Ishida R. ICRF-193, a catalytic inhibitor of DNA topoisomerase II, delays the cell cycle progression from metaphase, but not from anaphase to the G1 phase in mammalian cells. FEBS Lett 1997; 406(3): 267-70.
[http://dx.doi.org/10.1016/S0014-5793(97)00282-2] [PMID: 9136899]
[100]
Hasinoff BB, Creighton AM, Kozlowska H, Thampatty P, Allan WP, Yalowich JC. Mitindomide is a catalytic inhibitor of DNA topoisomerase II that acts at the bisdioxopiperazine binding site. Mol Pharmacol 1997; 52(5): 839-45.
[http://dx.doi.org/10.1124/mol.52.5.839] [PMID: 9351975]
[101]
Gareth J. Morgan, and Faith E Davies. Bortezomib (Velcade™) in the treatment of multiple myeloma. Ther Clin Risk Manag 2006; 2(3): 271-9.
[http://dx.doi.org/10.2147/tcrm.2006.2.3.271] [PMID: 18360602]
[102]
Nakamura N. Emerging new roles of GM130, a cis-Golgi matrix protein, in higher order cell functions. J Pharmacol Sci 2010; 112(3): 255-64.
[http://dx.doi.org/10.1254/jphs.09R03CR] [PMID: 20197635]
[103]
Mekhail TM, Markman M. Paclitaxel in cancer therapy. Expert Opin Pharmacother 2002; 3(6): 755-66.
[http://dx.doi.org/10.1517/14656566.3.6.755] [PMID: 12036415]
[104]
Trendowski M. Using cytochalasins to improve current chemotherapeutic approaches. Anticancer Agents Med Chem 2015; 15(3): 327-35.
[http://dx.doi.org/10.2174/1871520614666141016164335] [PMID: 25322987]
[105]
Medina VA, Rivera ES. Histamine receptors and cancer pharmacology. Br J Pharmacol 2010; 161(4): 755-67.
[http://dx.doi.org/10.1111/j.1476-5381.2010.00961.x] [PMID: 20636392]
[106]
Christman JK. 5-Azacytidine and 5-aza-2′-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy. Oncogene 2002; 21(35): 5483-95.
[http://dx.doi.org/10.1038/sj.onc.1205699] [PMID: 12154409]
[107]
Zhang X, Fryknäs M, Hernlund E, et al. Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments. Nat Commun 2014; 5: 3295.
[http://dx.doi.org/10.1038/ncomms4295] [PMID: 24548894]
[108]
Grignani G, Palmerini E, Ferraresi V, et al. Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment: a non-randomised phase 2 clinical trial. Lancet Oncol 2015; 16(1): 98-107.
[http://dx.doi.org/10.1016/S1470-2045(14)71136-2] [PMID: 25498219]
[109]
Błaszczak-Świątkiewicz K, Olszewska P, Mikiciuk-Olasik E. Antiproliferative activity of new benzimidazole derivatives. Acta Biochim Pol 2013; 60(3): 427-33.
[http://dx.doi.org/10.18388/abp.2013_2003] [PMID: 23888297]
[110]
Meng C, Zhu H, Song H, et al. Targets and molecular mechanisms of triptolide in cancer therapy. Chin J Cancer Res 2014; 26(5): 622-6.
[PMID: 25400429]
[111]
Yang T, Yao H, He G, et al. Effects of Lovastatin on MDA-MB-231 Breast Cancer Cells: An Antibody Microarray Analysis. J Cancer 2016; 7(2): 192-9.
[http://dx.doi.org/10.7150/jca.13414] [PMID: 26819643]
[112]
Williams CS, Sheng H, Brockman JA, et al. A cyclooxygenase-2 inhibitor (SC-58125) blocks growth of established human colon cancer xenografts. Neoplasia 2001; 3(5): 428-36.
[http://dx.doi.org/10.1038/sj.neo.7900177] [PMID: 11687954]
[113]
Ochel H-J, Eichhorn K, Gademann G. Geldanamycin: the prototype of a class of antitumor drugs targeting the heat shock protein 90 family of molecular chaperones. Cell Stress Chaperones 2001; 6(2): 105-12.
[http://dx.doi.org/10.1379/1466-1268(2001)006<0105:GTPOAC>2.0.CO;2] [PMID: 11599571]
[114]
Bansal D, Badhan Y, Gudala K, Schifano F. Ruboxistaurin for the treatment of diabetic peripheral neuropathy: a systematic review of randomized clinical trials. Diabetes Metab J 2013; 37(5): 375-84.
[http://dx.doi.org/10.4093/dmj.2013.37.5.375] [PMID: 24199167]
[115]
Wilder RL. Integrin alpha V beta 3 as a target for treatment of rheumatoid arthritis and related rheumatic diseases. Ann Rheum Dis 2002; 61(Suppl. 2): ii96-9.
[http://dx.doi.org/10.1136/ard.61.suppl_2.ii96] [PMID: 12379637]
[116]
Lieberman A, Goldstein M, Neophytides A, et al. Lisuride in Parkinson disease: efficacy of lisuride compared to levodopa. Neurology 1981; 31(8): 961-5.
[http://dx.doi.org/10.1212/WNL.31.8.961] [PMID: 7022259]
[117]
Liu Z, Hamamichi S, Lee BD, et al. Inhibitors of LRRK2 kinase attenuate neurodegeneration and Parkinson-like phenotypes in Caenorhabditis elegans and Drosophila Parkinson’s disease models. Hum Mol Genet 2011; 20(20): 3933-42.
[http://dx.doi.org/10.1093/hmg/ddr312] [PMID: 21768216]
[118]
Imbriglio JE, Chang S, Liang R, et al. GPR109a agonists. Part 1: 5-Alkyl and 5-aryl-pyrazole-tetrazoles as agonists of the human orphan G-protein coupled receptor GPR109a. Bioorg Med Chem Lett 2009; 19(8): 2121-4.
[http://dx.doi.org/10.1016/j.bmcl.2009.03.014] [PMID: 19307116]
[119]
Chen L, Bush CR, Necela BM, et al. RS5444, a novel PPARgamma agonist, regulates aspects of the differentiated phenotype in nontransformed intestinal epithelial cells. Mol Cell Endocrinol 2006; 251(1-2): 17-32.
[http://dx.doi.org/10.1016/j.mce.2006.02.006] [PMID: 16574311]
[120]
Francardo V. Sigma-1 receptor: a potential new target for Parkinson’s disease? Neural Regen Res 2014; 9(21): 1882-3.
[http://dx.doi.org/10.4103/1673-5374.145351] [PMID: 25558236]
[121]
Bose A, Beal MF. Mitochondrial dysfunction in Parkinson’s disease. J Neurochem 2016; 139(139)(Suppl. 1): 216-31.
[http://dx.doi.org/10.1111/jnc.13731] [PMID: 27546335]