Issue
Expression characteristics of peripheral blood genes reveal potential biomarkers and candidate therapeutic targets for Parkinson's disease
Corresponding Author(s) : Longyou Zhao
Cellular and Molecular Biology,
Vol. 66 No. 2: Issue 2
Abstract
In neurodegenerative disease, Parkinson's disease is the second most common one. Current demographic trends tell that by 2030, the risk of prevalence is close to 4% and the incidence is expected to double. Understanding the detailed process of Parkinson's disease can help us to figure out new biomarkers and candidate therapeutic targets for the diagnosis and progression of PD. This study is based on modularity for in-depth analysis and exploration of critical genes in the pathogenesis of Parkinson's disease, intended to identify the molecular processes of Parkinson's disease. According to the hypergeometric test, by performing differential analysis, enrichment analysis, co-expression module analysis, network connectivity analysis and finally, the ncRNA (non-coding RNA) and transcription factor that regulate the module were predicted. Based on the above methods, we obtained ten co-expression modules, including 2180 differential genes. Among them, RB1, IL7, and other genes were significantly differentially expressed in PD patients, and they had existing regulation in dysfunction modules, which was identified as Key genes in PD. The biological processes involved in the modular genes, for example, regulate lymphocyte activation, signal release, cellular calcium homeostasis, regulation of inflammatory responses, and regulation of exocytosis. This behavior significantly regulates signaling pathways such as cytokine-cytokine receptor interactions. Further, we identified ncRNA pivot including miR-25-3p. Also, transcription Factors pivot such as RELA, STAT1 significantly regulate dysfunction modules. This study can help to reveal all Parkinson's core dysfunction modules and potential regulatory factors as well as essential genes and the study assists to improve our understanding of its pathogenesis. The study can also be used to determine treatment goals and measure the effectiveness of interventions to provide predictive biomarkers and candidate therapeutic targets.
Keywords
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- Johnson KE. Approach to the patient with Parkinson disease. Prim Care 2015; 42(2): 205-215.
- Tarsy D. Treatment of Parkinson disease: a 64-year-old man with motor complications of advanced Parkinson disease. JAMA 2012; 307(21): 2305-2314.
- Haltenhof H, Schroter C. Depression in Parkinson disease. A literature review. Fortschr Neurol Psychiatr 1994; 62(3): 94-101.
- Danielczyk W. Psychological changes in Parkinson disease. Wien Med Wochenschr 1986; 136(15-16): 396-399.
- Zhang M, Mu H, Shang Z, Kang K, Lv H, Duan L, Li J, Chen X, Teng Y, Jiang Y, Zhang R. Genome-wide pathway-based asso¬ciation analysis identifies risk pathways associated with Parkinson's disease. Neuroscience 2017; 340: 398-410.
- Lill CM, Klein C. Epidemiology and causes of Parkinson's di¬sease. Nervenarzt 2017; 88(4): 345-355.
- Kim HJ. Alpha-Synuclein Expression in Patients with Parkin¬son's Disease: A Clinician's Perspective. Exp Neurobiol 2013; 22(2): 77-83.
- Yang X, Zhao Q, An R, Zhou H, Lin Z, Xu, Y. SNP rs1805874 of the Calbindin1 Gene Is Associated with Parkinson's Disease in Han Chinese. Genet Test Mol Biomarkers 2016; 20(12): 753-757.
- Rozenkrantz L, Gan-Or Z, Gana-Weisz M, Mirelman A, Giladi N, Bar-Shira A, Orr-Urtreger A. SEPT14 Is Associated with a Re¬duced Risk for Parkinson's Disease and Expressed in Human Brain. J Mol Neurosci 2016; 59(3): 343-350.
- Zhu ZG, Ai QL, Wang WM, Xiao ZC. Meta-analysis supports association of a functional SN Meta-analysis supports association of a functional SNP (rs1801133) in the MTHFR gene with Parkinson's disease. Gene 2013; 531(1): 78-83.
- Han W, Liu Y, Mi Y, Zhao J, Liu D, Tian QB. Alpha-synuclein (SNCA) polymorphisms and susceptibility to Parkinson's disease: a meta-analysis. Am J Med Genet B Neuropsychiatr Genet 2015; 168B(2): 123-134.
- Chen K, Chen YP, Song W, Huang R, Zhao B, Cao B, Yang Y, Satake W, Toda T, Shang HF. Association analysis of LRP8 SNP rs3820198 and rs5174 with Parkinson's disease in Han Chinese po¬pulation. Neurol Res 2012; 34(7): 725-729.
- Tarale P, Daiwile AP, Sivanesan S, Stöger R, Bafana A, Nao¬ghare PK, Parmar D, Chakrabarti T, Krishnamurthi K. Manganese exposure: Linking down-regulation of miRNA-7 and miRNA-433 with alpha-synuclein overexpression and risk of idiopathic Parkin¬son's disease. Toxicol In Vitro 2018; 46: 94-101.
- Caggiu E, Paulus K, Mameli G, Arru G, Sechi GP, Sechi LA. Differential expression of miRNA 155 and miRNA 146a in Parkin¬son's disease patients. eNeurologicalSci 2018; 13: 1-4.
- Liu Y, Song Y, Zhu X. MicroRNA-181a Regulates Apoptosis and Autophagy Process in Parkinson's Disease by Inhibiting p38 Mi¬togen-Activated Protein Kinase (MAPK)/c-Jun N-Terminal Kinases (JNK) Signaling Pathways. Med Sci Monit 2017; 23: 1597-1606.
- Wang S, Zhang X, Guo Y, Rong H, Liu T. The long nonco¬ding RNA HOTAIR promotes Parkinson's disease by upregulating LRRK2 expression. Oncotarget 2017; 8(15): 24449-24456.
- Zhang QS, Wang ZH, Zhang JL, Duan YL, Li GF, Zheng DL. Beta-asarone protects against MPTP-induced Parkinson's disease via regulating long non-coding RNA MALAT1 and inhibiting alpha-synuclein protein expression. Biomed Pharmacother 2016; 83: 153- 159.
- Wang Y, Yang Z, Le W. Tiny But Mighty: Promising Roles of MicroRNAs in the Diagnosis and Treatment of Parkinson's Disease. Neurosci Bull 2017; 33(5): 543-551.
- Lim SY, Fox SH, Lang AE. Overview of the extranigral aspects of Parkinson disease. Arch Neurol 2009; 66(2): 167-172.
- Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, To¬mashevsky M, Marshall KA, Phillippy KH, Sherman PM, Holko M, Yefanov A, Lee H, Zhang N, Robertson CL, Serova N, Davis S, Soboleva A. (2012). NCBI GEO: archive for functional genomics data sets”update. Nucleic Acids Res 2012; 41(D1): D991-D995.
- Alieva AK, Shadrina MI, Filatova EV, Karabanov AV, Illariosh¬kin SN, Limborska SA, Slominsky PA. Involvement of endocytosis and alternative splicing in the formation of the pathological process in the early stages of Parkinson's disease. Biomed Res Int 2014; 2014: 1-7.
- Yi Y, Zhao Y, Li C, Zhang L, Huang H, Li Y, Liu L, Hou P, Cui T, Tan P, Hu Y, Zhang T, Huang Y, Li X, Yu J, Wang D. RAID v2.0: an updated resource of RNA-associated interactions across organisms. Nucleic Acids Res 2017; 45(D1): D115-D118.
- Han H, Cho JW, Lee S, Yun A, Kim H, Bae D, Yang S, Kim CY, Lee M, Kim E, Lee S, Kang B, Jeong D, Kim Y, Jeon HN, Jung H, Nam S, Chung M, Kim JH, Lee I. TRRUST v2: an expanded reference database of human and mouse transcriptional regulatory interactions. Nucleic Acids Res 2018; 46(D1): D380-D386.
- Ritchie ME, Phipson B, Wu DI, Hu Y, Law CW, Shi W, Smyth GK. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 2015; 43(7): e47.
- Law CW, Chen Y, Shi W, Smyth GK. voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Ge¬nome Biol 2014; 15(2): R29-R45.
- Smyth GK. Linear models and empirical bayes methods for as¬sessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 2004; 3(1): 1-25.
- Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 2008; 9: 559- 571.
- Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 2012; 16(5): 284-287.
- Maere S, Heymans K, Kuiper M. BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics 2005; 21(16): 3448-3449.
- Abe N, Mori E. (Cognitive impairment in patients with Parkin¬son disease). Brain Nerve 2012; 64(4): 321-331.
- Coon EA, Low PA. Thermoregulation in Parkinson disease. Handb Clin Neurol 2018; 157: 715-725.
- Contreras F, Prado C, González H, Franz D, Osorio-Barrios F, Osorio F, Ugalde V, Lopez E, Elgueta D, Figueroa A, Lladser A, Pacheco R. Dopamine Receptor D3 Signaling on CD4+ T Cells Fa¬vors Th1- and Th17-Mediated Immunity. J Immunol 2016; 196(10): 4143-4149.
- Mattson MP. Calcium and neurodegeneration. Aging Cell 2007; 6(3): 337-750.
- Paillusson S, Gomez-Suaga P, Stoica R, Little D, Gissen P, De¬vine MJ, Noble W, Hanger DP, Miller CCJ. alpha-Synuclein binds to the ER-mitochondria tethering protein VAPB to disrupt Ca(2+) homeostasis and mitochondrial ATP production. Acta Neuropathol 2017; 134(1): 129-149.
- Yan J, Fu Q, Cheng L, Zhai M, Wu W, Huang L, Du G. Inflam¬matory response in Parkinson's disease (Review). Mol Med Rep 2014; 10(5): 2223-2233.
- Jiang TF, Chen SD. Dysfunction of two lysosome degradation pathways of alpha-synuclein in Parkinson's disease: potential thera¬peutic targets? Neurosci Bull 2012; 28(5): 649-657.
- Dey R, Ji K, Liu Z, Chen L. A cytokine-cytokine interaction in the assembly of higher-order structure and activation of the interleu¬kine-3:receptor complex. PLoS One 2009; 4(4): e5188-e5199.
- Rivero-Ríos P, Madero-Pérez J, Fernández B, Hilfiker S. Targe¬ting the Autophagy/Lysosomal Degradation Pathway in Parkinson's Disease. Curr Neuropharmacol 2016; 14(3): 238-249.
- Shao S, Wang GL, Raymond C, Deng XH, Zhu XL, Wang DI, Hong LP. Activation of Sonic hedgehog signal by Purmorphamine, in a mouse model of Parkinson's disease, protects dopaminergic neu¬rons and attenuates inflammatory response by mediating PI3K/AKt signaling pathway. Mol Med Rep 2017; 16(2): 1269-1277.
- Serafino A, Sferrazza G, Colini Baldeschi A, Nicotera G, An¬dreola F, Pittaluga E, Pierimarchi P. Developing drugs that target the Wnt pathway: recent approaches in cancer and neurodegenerative diseases. Expert Opin Drug Discov 2017; 12(2): 169-186.
- Zhang YL, Liu Y, Kang XP, Dou CY, Zhuo RG, Huang SQ, Peng L, Wen L. Ginsenoside Rb1 confers neuroprotection via promotion of glutamate transporters in a mouse model of Parkinson's disease. Neuropharmacology 2018; 131: 223-237.
- Lin J, Zhu Z, Xiao H, Wakefield MR, Ding VA, Bai Q, Fang Y. The role of IL-7 in Immunity and Cancer. Anticancer Res 2017; 37(3): 963-967.
- Song J, Li Y. miR-25-3p reverses epithelial-mesenchymal tran¬sition via targeting Sema4C in cisplatin-resistance cervical cancer cells. Cancer Sci 2017; 108(1): 23-31.
- Chen H, Pan H, Qian Y, Zhou W, Liu X. MiR-25-3p promotes the proliferation of triple negative breast cancer by targeting BTG2. Mol Cancer 2018; 17(1): 4-14.
- Zhang F, Chen K, Tao H, Kang T, Xiong Q, Zeng Q, Liu Y, Jiang S, Chen M. miR-25-3p, Positively Regulated by Transcription Factor AP-2alpha, Regulates the Metabolism of C2C12 Cells by Tar¬geting Akt1. Int J Mol Sci 2018; 19(3): 1-13.
- Xu JY, Yang LL, Ma C, Huang YL, Zhu GX, Chen QL. MiR-25- 3p attenuates the proliferation of tongue squamous cell carcinoma cell line Tca8113. Asian Pac J Trop Med 2013; 6(9): 743-747.
- Liang Y, Lin Q, Huang P, Wang Y, Li J, Zhang L and Cao J: Rice Bioactive Peptide Binding with TLR4 To Overcome H2O2-Induced Injury in Human Umbilical Vein Endothelial Cells through NF-κB Signaling. J Agri Food Chem 2018; 66(2): 440-448.
- Wang L, Lin Q, Yang T, Liang Y, Nie Y, Luo Y and Luo F. Oryza¬nol modifies high fat diet-induced obesity, liver gene expression pro¬file, and inflammation response in mice. J Agri Food Chem 2017; 65(38): 8374-8385.
- Lou Y, Shi J, Guo D, Qureshi AK and Song L. Function of PD-L1 in antitumor immunity of glioma cells. Saudi J Boil Sci 2017; 24(4): 803-807.
- Guo T, Lin Q, Li X, Nie Y, Wang L, Shi L and Luo F. Octacosa¬nol attenuates inflammation in both RAW264. 7 macrophages and a mouse model of colitis. J Agri Food Chem 2017; 65(18): 3647-3658.
- Li W, Jia MX, Wang JH, Lu JL, Deng J, Tang JX and Liu C. As¬sociation of MMP9-1562C/T and MMP13-77A/G polymorphisms with non-small cell lung cancer in southern Chinese population. Biomol 2019; 9(3): 107-119.
- Nie Y, Luo F, Wang L, Yang T, Shi L, Li X, Shen J, Xu W, Guo T and Lin Q. Anti-hyperlipidemic effect of rice bran polysaccharide and its potential mechanism in high-fat diet mice. Food Func 2017; 8(11): 4028-4041.
- Choi DC, Chae YJ, Kabaria S, Chaudhuri AD, Jain MR, Li H, Mouradian MM, Junn E. MicroRNA-7 protects against 1-methyl- 4-phenylpyridinium-induced cell death by targeting RelA. J Neu¬rosci 2014; 34(38): 12725-12737.
- Chaudhuri AD, Kabaria S, Choi DC, Mouradian MM, Junn E. MicroRNA-7 Promotes Glycolysis to Protect against 1-Methyl- 4-phenylpyridinium-induced Cell Death. J Biol Chem 2015; 290(19): 12425-12434.
- Hou L, Zhou X, Zhang C, Wang K, Liu X, Che Y, Sun F, Li H, Wang Q, Zhang D, Hong JS. NADPH oxidase-derived H2O2 mediates the regulatory effects of microglia on astrogliosis in expe¬rimental models of Parkinson's disease. Redox Biol 2017; 12: 162- 170.
- Qin H, Buckley JA, Li X, Liu Y, Fox TH, Meares GP, Yu H, Yan Z, Harms AS, Li Y, Standaert DG, Benveniste EN. Inhibition of the JAK/STAT Pathway Protects Against alpha-Synuclein-Induced Neuroinflammation and Dopaminergic Neurodegeneration. J Neu¬rosci 2016; 36(18): 5144-5159.
- Lou Y, Yang J, Wang L, Chen X, Xin X and Liu Y. The clini¬cal efficacy study of treatment to Chiari malformation type I with syringomyelia under the minimally invasive surgery of resection of Submeningeal cerebellar Tonsillar Herniation and reconstruction of Cisterna magna. Saudi J Biol Sci 2019; 26(8): 1927-1931.
- Lou Y, Guo D, Zhang H and Song L. Effectiveness of mesenchy¬mal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression. Open Life Sci 2016; 11(1): 519-523.
- Chen X, Xu Y, Meng L, Chen X, Yuan L, Cai Q, Shi W and Huang G. Non-parametric partial least squares–discriminant analy-sis model based on sum of ranking difference algorithm for tea grade identification using electronic tongue data identify tea grade using e-tongue data. Sens Actuators B Chem 2020; 127924.
- Nie Y, Luo F and Lin Q. Dietary nutrition and gut microflora: A promising target for treating diseases. Trends Food Sci Technol 2018;75: 72-80.
- Ren Y, Jiao X and Zhang L. Expression level of fibroblast growth factor 5 (FGF5) in the peripheral blood of primary hypertension and its clinical significance. Saudi J Biol Sci 2018; 25(3): 469-473.
References
Johnson KE. Approach to the patient with Parkinson disease. Prim Care 2015; 42(2): 205-215.
Tarsy D. Treatment of Parkinson disease: a 64-year-old man with motor complications of advanced Parkinson disease. JAMA 2012; 307(21): 2305-2314.
Haltenhof H, Schroter C. Depression in Parkinson disease. A literature review. Fortschr Neurol Psychiatr 1994; 62(3): 94-101.
Danielczyk W. Psychological changes in Parkinson disease. Wien Med Wochenschr 1986; 136(15-16): 396-399.
Zhang M, Mu H, Shang Z, Kang K, Lv H, Duan L, Li J, Chen X, Teng Y, Jiang Y, Zhang R. Genome-wide pathway-based asso¬ciation analysis identifies risk pathways associated with Parkinson's disease. Neuroscience 2017; 340: 398-410.
Lill CM, Klein C. Epidemiology and causes of Parkinson's di¬sease. Nervenarzt 2017; 88(4): 345-355.
Kim HJ. Alpha-Synuclein Expression in Patients with Parkin¬son's Disease: A Clinician's Perspective. Exp Neurobiol 2013; 22(2): 77-83.
Yang X, Zhao Q, An R, Zhou H, Lin Z, Xu, Y. SNP rs1805874 of the Calbindin1 Gene Is Associated with Parkinson's Disease in Han Chinese. Genet Test Mol Biomarkers 2016; 20(12): 753-757.
Rozenkrantz L, Gan-Or Z, Gana-Weisz M, Mirelman A, Giladi N, Bar-Shira A, Orr-Urtreger A. SEPT14 Is Associated with a Re¬duced Risk for Parkinson's Disease and Expressed in Human Brain. J Mol Neurosci 2016; 59(3): 343-350.
Zhu ZG, Ai QL, Wang WM, Xiao ZC. Meta-analysis supports association of a functional SN Meta-analysis supports association of a functional SNP (rs1801133) in the MTHFR gene with Parkinson's disease. Gene 2013; 531(1): 78-83.
Han W, Liu Y, Mi Y, Zhao J, Liu D, Tian QB. Alpha-synuclein (SNCA) polymorphisms and susceptibility to Parkinson's disease: a meta-analysis. Am J Med Genet B Neuropsychiatr Genet 2015; 168B(2): 123-134.
Chen K, Chen YP, Song W, Huang R, Zhao B, Cao B, Yang Y, Satake W, Toda T, Shang HF. Association analysis of LRP8 SNP rs3820198 and rs5174 with Parkinson's disease in Han Chinese po¬pulation. Neurol Res 2012; 34(7): 725-729.
Tarale P, Daiwile AP, Sivanesan S, Stöger R, Bafana A, Nao¬ghare PK, Parmar D, Chakrabarti T, Krishnamurthi K. Manganese exposure: Linking down-regulation of miRNA-7 and miRNA-433 with alpha-synuclein overexpression and risk of idiopathic Parkin¬son's disease. Toxicol In Vitro 2018; 46: 94-101.
Caggiu E, Paulus K, Mameli G, Arru G, Sechi GP, Sechi LA. Differential expression of miRNA 155 and miRNA 146a in Parkin¬son's disease patients. eNeurologicalSci 2018; 13: 1-4.
Liu Y, Song Y, Zhu X. MicroRNA-181a Regulates Apoptosis and Autophagy Process in Parkinson's Disease by Inhibiting p38 Mi¬togen-Activated Protein Kinase (MAPK)/c-Jun N-Terminal Kinases (JNK) Signaling Pathways. Med Sci Monit 2017; 23: 1597-1606.
Wang S, Zhang X, Guo Y, Rong H, Liu T. The long nonco¬ding RNA HOTAIR promotes Parkinson's disease by upregulating LRRK2 expression. Oncotarget 2017; 8(15): 24449-24456.
Zhang QS, Wang ZH, Zhang JL, Duan YL, Li GF, Zheng DL. Beta-asarone protects against MPTP-induced Parkinson's disease via regulating long non-coding RNA MALAT1 and inhibiting alpha-synuclein protein expression. Biomed Pharmacother 2016; 83: 153- 159.
Wang Y, Yang Z, Le W. Tiny But Mighty: Promising Roles of MicroRNAs in the Diagnosis and Treatment of Parkinson's Disease. Neurosci Bull 2017; 33(5): 543-551.
Lim SY, Fox SH, Lang AE. Overview of the extranigral aspects of Parkinson disease. Arch Neurol 2009; 66(2): 167-172.
Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, To¬mashevsky M, Marshall KA, Phillippy KH, Sherman PM, Holko M, Yefanov A, Lee H, Zhang N, Robertson CL, Serova N, Davis S, Soboleva A. (2012). NCBI GEO: archive for functional genomics data sets”update. Nucleic Acids Res 2012; 41(D1): D991-D995.
Alieva AK, Shadrina MI, Filatova EV, Karabanov AV, Illariosh¬kin SN, Limborska SA, Slominsky PA. Involvement of endocytosis and alternative splicing in the formation of the pathological process in the early stages of Parkinson's disease. Biomed Res Int 2014; 2014: 1-7.
Yi Y, Zhao Y, Li C, Zhang L, Huang H, Li Y, Liu L, Hou P, Cui T, Tan P, Hu Y, Zhang T, Huang Y, Li X, Yu J, Wang D. RAID v2.0: an updated resource of RNA-associated interactions across organisms. Nucleic Acids Res 2017; 45(D1): D115-D118.
Han H, Cho JW, Lee S, Yun A, Kim H, Bae D, Yang S, Kim CY, Lee M, Kim E, Lee S, Kang B, Jeong D, Kim Y, Jeon HN, Jung H, Nam S, Chung M, Kim JH, Lee I. TRRUST v2: an expanded reference database of human and mouse transcriptional regulatory interactions. Nucleic Acids Res 2018; 46(D1): D380-D386.
Ritchie ME, Phipson B, Wu DI, Hu Y, Law CW, Shi W, Smyth GK. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 2015; 43(7): e47.
Law CW, Chen Y, Shi W, Smyth GK. voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Ge¬nome Biol 2014; 15(2): R29-R45.
Smyth GK. Linear models and empirical bayes methods for as¬sessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 2004; 3(1): 1-25.
Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 2008; 9: 559- 571.
Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 2012; 16(5): 284-287.
Maere S, Heymans K, Kuiper M. BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics 2005; 21(16): 3448-3449.
Abe N, Mori E. (Cognitive impairment in patients with Parkin¬son disease). Brain Nerve 2012; 64(4): 321-331.
Coon EA, Low PA. Thermoregulation in Parkinson disease. Handb Clin Neurol 2018; 157: 715-725.
Contreras F, Prado C, González H, Franz D, Osorio-Barrios F, Osorio F, Ugalde V, Lopez E, Elgueta D, Figueroa A, Lladser A, Pacheco R. Dopamine Receptor D3 Signaling on CD4+ T Cells Fa¬vors Th1- and Th17-Mediated Immunity. J Immunol 2016; 196(10): 4143-4149.
Mattson MP. Calcium and neurodegeneration. Aging Cell 2007; 6(3): 337-750.
Paillusson S, Gomez-Suaga P, Stoica R, Little D, Gissen P, De¬vine MJ, Noble W, Hanger DP, Miller CCJ. alpha-Synuclein binds to the ER-mitochondria tethering protein VAPB to disrupt Ca(2+) homeostasis and mitochondrial ATP production. Acta Neuropathol 2017; 134(1): 129-149.
Yan J, Fu Q, Cheng L, Zhai M, Wu W, Huang L, Du G. Inflam¬matory response in Parkinson's disease (Review). Mol Med Rep 2014; 10(5): 2223-2233.
Jiang TF, Chen SD. Dysfunction of two lysosome degradation pathways of alpha-synuclein in Parkinson's disease: potential thera¬peutic targets? Neurosci Bull 2012; 28(5): 649-657.
Dey R, Ji K, Liu Z, Chen L. A cytokine-cytokine interaction in the assembly of higher-order structure and activation of the interleu¬kine-3:receptor complex. PLoS One 2009; 4(4): e5188-e5199.
Rivero-Ríos P, Madero-Pérez J, Fernández B, Hilfiker S. Targe¬ting the Autophagy/Lysosomal Degradation Pathway in Parkinson's Disease. Curr Neuropharmacol 2016; 14(3): 238-249.
Shao S, Wang GL, Raymond C, Deng XH, Zhu XL, Wang DI, Hong LP. Activation of Sonic hedgehog signal by Purmorphamine, in a mouse model of Parkinson's disease, protects dopaminergic neu¬rons and attenuates inflammatory response by mediating PI3K/AKt signaling pathway. Mol Med Rep 2017; 16(2): 1269-1277.
Serafino A, Sferrazza G, Colini Baldeschi A, Nicotera G, An¬dreola F, Pittaluga E, Pierimarchi P. Developing drugs that target the Wnt pathway: recent approaches in cancer and neurodegenerative diseases. Expert Opin Drug Discov 2017; 12(2): 169-186.
Zhang YL, Liu Y, Kang XP, Dou CY, Zhuo RG, Huang SQ, Peng L, Wen L. Ginsenoside Rb1 confers neuroprotection via promotion of glutamate transporters in a mouse model of Parkinson's disease. Neuropharmacology 2018; 131: 223-237.
Lin J, Zhu Z, Xiao H, Wakefield MR, Ding VA, Bai Q, Fang Y. The role of IL-7 in Immunity and Cancer. Anticancer Res 2017; 37(3): 963-967.
Song J, Li Y. miR-25-3p reverses epithelial-mesenchymal tran¬sition via targeting Sema4C in cisplatin-resistance cervical cancer cells. Cancer Sci 2017; 108(1): 23-31.
Chen H, Pan H, Qian Y, Zhou W, Liu X. MiR-25-3p promotes the proliferation of triple negative breast cancer by targeting BTG2. Mol Cancer 2018; 17(1): 4-14.
Zhang F, Chen K, Tao H, Kang T, Xiong Q, Zeng Q, Liu Y, Jiang S, Chen M. miR-25-3p, Positively Regulated by Transcription Factor AP-2alpha, Regulates the Metabolism of C2C12 Cells by Tar¬geting Akt1. Int J Mol Sci 2018; 19(3): 1-13.
Xu JY, Yang LL, Ma C, Huang YL, Zhu GX, Chen QL. MiR-25- 3p attenuates the proliferation of tongue squamous cell carcinoma cell line Tca8113. Asian Pac J Trop Med 2013; 6(9): 743-747.
Liang Y, Lin Q, Huang P, Wang Y, Li J, Zhang L and Cao J: Rice Bioactive Peptide Binding with TLR4 To Overcome H2O2-Induced Injury in Human Umbilical Vein Endothelial Cells through NF-κB Signaling. J Agri Food Chem 2018; 66(2): 440-448.
Wang L, Lin Q, Yang T, Liang Y, Nie Y, Luo Y and Luo F. Oryza¬nol modifies high fat diet-induced obesity, liver gene expression pro¬file, and inflammation response in mice. J Agri Food Chem 2017; 65(38): 8374-8385.
Lou Y, Shi J, Guo D, Qureshi AK and Song L. Function of PD-L1 in antitumor immunity of glioma cells. Saudi J Boil Sci 2017; 24(4): 803-807.
Guo T, Lin Q, Li X, Nie Y, Wang L, Shi L and Luo F. Octacosa¬nol attenuates inflammation in both RAW264. 7 macrophages and a mouse model of colitis. J Agri Food Chem 2017; 65(18): 3647-3658.
Li W, Jia MX, Wang JH, Lu JL, Deng J, Tang JX and Liu C. As¬sociation of MMP9-1562C/T and MMP13-77A/G polymorphisms with non-small cell lung cancer in southern Chinese population. Biomol 2019; 9(3): 107-119.
Nie Y, Luo F, Wang L, Yang T, Shi L, Li X, Shen J, Xu W, Guo T and Lin Q. Anti-hyperlipidemic effect of rice bran polysaccharide and its potential mechanism in high-fat diet mice. Food Func 2017; 8(11): 4028-4041.
Choi DC, Chae YJ, Kabaria S, Chaudhuri AD, Jain MR, Li H, Mouradian MM, Junn E. MicroRNA-7 protects against 1-methyl- 4-phenylpyridinium-induced cell death by targeting RelA. J Neu¬rosci 2014; 34(38): 12725-12737.
Chaudhuri AD, Kabaria S, Choi DC, Mouradian MM, Junn E. MicroRNA-7 Promotes Glycolysis to Protect against 1-Methyl- 4-phenylpyridinium-induced Cell Death. J Biol Chem 2015; 290(19): 12425-12434.
Hou L, Zhou X, Zhang C, Wang K, Liu X, Che Y, Sun F, Li H, Wang Q, Zhang D, Hong JS. NADPH oxidase-derived H2O2 mediates the regulatory effects of microglia on astrogliosis in expe¬rimental models of Parkinson's disease. Redox Biol 2017; 12: 162- 170.
Qin H, Buckley JA, Li X, Liu Y, Fox TH, Meares GP, Yu H, Yan Z, Harms AS, Li Y, Standaert DG, Benveniste EN. Inhibition of the JAK/STAT Pathway Protects Against alpha-Synuclein-Induced Neuroinflammation and Dopaminergic Neurodegeneration. J Neu¬rosci 2016; 36(18): 5144-5159.
Lou Y, Yang J, Wang L, Chen X, Xin X and Liu Y. The clini¬cal efficacy study of treatment to Chiari malformation type I with syringomyelia under the minimally invasive surgery of resection of Submeningeal cerebellar Tonsillar Herniation and reconstruction of Cisterna magna. Saudi J Biol Sci 2019; 26(8): 1927-1931.
Lou Y, Guo D, Zhang H and Song L. Effectiveness of mesenchy¬mal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression. Open Life Sci 2016; 11(1): 519-523.
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