Abstract
Parkinson's disease (PD) is a neurodegenerative disorder caused by the selective destruction of dopaminergic neurons (DA-nergic). Clinically, PD is diagnosed based on developing signs and symptoms. A neurological and physical examination and sometimes medical and family history also help in the diagnosis of PD. However, most of these features are visible when more than 80% of the dopaminergic neurons have degenerated. An understanding of the selective degeneration process at the cellular and molecular level and the development of new biomarkers are required for effective PD management. Several studies have been carried out using a selected set of miRNAs/ mRNAs and proteins to develop biomarkers of PD; however, an unbiased and combined miRNA–protein profiling study was required to identify the markers of progressive and selected degeneration of dopaminergic neurons in PD patients. In the present study, we have carried out global protein profiling through LC–MS/MS and miRNA profiling by using a “brain-specific” miRNA array panel of 112 miRNAs in PD patients and healthy controls to find the unprejudiced group of proteins and miRNAs that are deregulating in PD. In the whole blood samples of PD patients compared to healthy controls, the expression of 23 miRNAs and 289 proteins was significantly increased, whereas the expression of 4 miRNAs and 132 proteins was considerably downregulated. Network analysis, functional enrichment, annotation, and analysis of miRNA–protein interactions were also performed as part of the bioinformatics investigation of the discovered miRNAs and proteins revealing several pathways that lead to PD development and pathogenesis. Based on the analysis of miRNA and protein profiling, we have identified four miRNAs (hsa-miR-186-5p, miR-29b, miR-139 & has-miR-150-5p) and four proteins (YWHAZ, PSMA4, HYOU1, & SERPINA1), which can be targeted for the development of new biomarkers of PD. In vitro studies have identified the role of miR-186-5p in regulating the levels of the YWHAZ/YWHAB & CALM2 gene, which has shown maximum downregulation in PD patients and is known for its role in neuroprotection from apoptotic cell death & calcium regulation. In conclusion, our research has identified a group of miRNA–proteins that can be developed as PD biomarkers; however, future studies on the release of these miRNAs and proteins in extracellular vesicles circulating in the blood of PD patients can further validate these as specific biomarkers of PD.
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Data Availability
All the data generated or analyzed during the present study are included in this article and its supplementary information files.
Code Availability
NCBI-GEO accession number, GSE222480, and CCMS-MassIVE accession number, MSV000091013.
References
Agarwal V, Bell GW, Nam JW, Bartel DP (2015) Predicting effective microRNA target sites in mammalian mRNAs. eLife. https://doi.org/10.7554/eLife.05005
Ahn SM, Simpson RJ (2007) Body fluid proteomics: prospects for biomarker discovery. Proteomics Clin Appl 1(9):1004–1015. https://doi.org/10.1002/prca.200700217
Antón-Galindo E, Dalla Vecchia E, Orlandi JG, Castro G, Gualda EJ, Young AM, Aguado F, Loza-Alvarez P, Cormand B, Norton WH (2021) Deficiency of the ywhaz gene, involved in neurodevelopmental disorders, alters brain activity and behaviour in zebrafish. BioRxiv. https://doi.org/10.1101/2021.06.30.450513
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297. https://doi.org/10.1016/s0092-8674(04)00045-5
Berg D, Riess O, Bornemann A (2003) Specification of 14–3-3 proteins in Lewy bodies. Ann Neurol 54(1):135. https://doi.org/10.1002/ana.10621
Betarbet R, Canet-Aviles RM, Sherer TB, Mastroberardino PG, McLendon C, Kim JH, Lund S, Na HM, Taylor G, Bence NF, Kopito R, Seo BB, Yagi T, Yagi A, Klinefelter G, Cookson MR, Greenamyre JT (2006) Intersecting pathways to neurodegeneration in Parkinson’s disease: effects of the pesticide rotenone on DJ-1, alpha-synuclein, and the ubiquitin-proteasome system. Neurobiol Dis 22(2):404–420. https://doi.org/10.1016/j.nbd.2005.12.003
Bonnet R, Pavlovic S, Lehmann J, Rommelspacher H (2004) The strong inhibition of triosephosphate isomerase by the natural beta-carbolines may explain their neurotoxic actions. Neuroscience 127(2):443–453. https://doi.org/10.1016/j.neuroscience.2004.05.002
Botta-Orfila T, Morató X, Compta Y, Lozano JJ, Falgàs N, Valldeoriola F, Pont-Sunyer C, Vilas D, Mengual L, Fernández M, Molinuevo JL, Antonell A, Martí MJ, Fernández-Santiago R, Ezquerra M (2014) Identification of blood serum micro-RNAs associated with idiopathic and LRRK2 Parkinson’s disease. J Neurosci Res 92(8):1071–1077. https://doi.org/10.1002/jnr.23377
Cabeza-Arvelaiz Y, Schiestl RH (2012) Transcriptome analysis of a rotenone model of parkinsonism reveals complex I-tied and -untied toxicity mechanisms common to neurodegenerative diseases. PLoS one 7(9):e44700. https://doi.org/10.1371/journal.pone.0044700
Cai R, Zhang Y, Simmering JE, Schultz JL, Li Y, Fernandez-Carasa I, Consiglio A, Raya A, Polgreen PM, Narayanan NS, Yuan Y, Chen Z, Su W, Han Y, Zhao C, Gao L, Ji X, Welsh MJ, Liu L (2019) Enhancing glycolysis attenuates Parkinson’s disease progression in models and clinical databases. J Clin Investig 129(10):4539–4549. https://doi.org/10.1172/jci129987
Cao XY, Lu JM, Zhao ZQ, Li MC, Lu T, An XS, Xue LJ (2017) MicroRNA biomarkers of Parkinson’s disease in serum exosome-like microvesicles. Neurosci Lett 644:94–99. https://doi.org/10.1016/j.neulet.2017.02.045
Chahine LM, Stern MB, Chen-Plotkin A (2014) Blood-based biomarkers for Parkinson’s disease. Parkinsonism Relat Disord 20(1):S99-103. https://doi.org/10.1016/s1353-8020(13)70025-7
da Huang W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44–57. https://doi.org/10.1038/nprot.2008.211
Deng X, Lin Z, Zuo C, Fu Y (2020) Upregulation of miR-150-5p alleviates LPS-induced inflammatory response and apoptosis of RAW2647 macrophages by targeting Notch1. Open Life Sci 15(1):544–552. https://doi.org/10.1515/biol-2020-0058
Dickson DW (2018) Neuropathology of Parkinson disease. Parkinsonism Relat Disord 46(Suppl 1):S30–S33. https://doi.org/10.1016/j.parkreldis.2017.07.033
Ebbert MTW, Ross CA, Pregent LJ, Lank RJ, Zhang C, Katzman RB, Jansen-West K, Song Y, da Rocha EL, Palmucci C, Desaro P, Robertson AE, Caputo AM, Dickson DW, Boylan KB, Rademakers R, Ordog T, Li H, Belzil VV (2017) Conserved DNA methylation combined with differential frontal cortex and cerebellar expression distinguishes C9orf72-associated and sporadic ALS, and implicates SERPINA1 in disease. Acta Neuropathol 134(5):715–728. https://doi.org/10.1007/s00401-017-1760-4
Gettins PG (2002) Serpin structure, mechanism, and function. Chem Rev 102(12):4751–4804. https://doi.org/10.1021/cr010170+
Gold M, Dolga AM, Koepke J, Mengel D, Culmsee C, Dodel R, Koczulla AR, Bach JP (2014) α1-antitrypsin modulates microglial-mediated neuroinflammation and protects microglial cells from amyloid-β-induced toxicity. J Neuroinflammation 11:165. https://doi.org/10.1186/s12974-014-0165-8
Gollin PA, Kalaria RN, Eikelenboom P, Rozemuller A, Perry G (1992) Alpha 1-antitrypsin and alpha 1-antichymotrypsin are in the lesions of Alzheimer’s disease. NeuroReport 3(2):201–203. https://doi.org/10.1097/00001756-199202000-00020
Halbgebauer S, Nagl M, Klafki H, Haußmann U, Steinacker P, Oeckl P, Kassubek J, Pinkhardt E, Ludolph AC, Soininen H, Herukka SK, Wiltfang J, Otto M (2016) Modified serpinA1 as risk marker for Parkinson’s disease dementia: analysis of baseline data. Sci Rep 6:26145. https://doi.org/10.1038/srep26145
Higgins NR, Greenslade JE, Wu JJ, Miranda E, Galliciotti G, Monteiro MJ (2021) Serpin neuropathology in the P497S UBQLN2 mouse model of ALS/FTD. Brain Pathol (Zurich, Switzerland) 31(5):e12948. https://doi.org/10.1111/bpa.12948
Hirsch EC, Jenner P, Przedborski S (2013) Pathogenesis of Parkinson’s disease. Mov Disord 28(1):24–30. https://doi.org/10.1002/mds.25032
Hurley MJ, Brandon B, Gentleman SM, Dexter DT (2013) Parkinson’s disease is associated with altered expression of CaV1 channels and calcium-binding proteins. Brain 136(Pt 7):2077–2097. https://doi.org/10.1093/brain/awt134
Jankovic J (2008) Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 79(4):368–376. https://doi.org/10.1136/jnnp.2007.131045
Jankovic J, Tan EK (2020) Parkinson’s disease: etiopathogenesis and treatment. J Neurol Neurosurg Psychiatry 91(8):795–808. https://doi.org/10.1136/jnnp-2019-322338
Jauhari A, Singh T, Pandey A, Singh P, Singh N, Srivastava AK, Pant AB, Parmar D, Yadav S (2017) Differentiation induces dramatic changes in miRNA profile, where loss of dicer diverts differentiating SH-SY5Y cells toward senescence. Mol Neurobiol 54(7):4986–4995. https://doi.org/10.1007/s12035-016-0042-9
Jauhari A, Singh T, Mishra S, Shankar J, Yadav S (2020) Coordinated action of miR-146a and parkin gene regulate rotenone-induced neurodegeneration. Toxicol Sci 176(2):433–445. https://doi.org/10.1093/toxsci/kfaa066
Jesse S, Lehnert S, Jahn O, Parnetti L, Soininen H, Herukka SK, Steinacker P, Tawfik S, Tumani H, von Arnim CA, Neumann M, Kretzschmar HA, Kulaksiz H, Lenter M, Wiltfang J, Ferger B, Hengerer B, Otto M (2012) Differential sialylation of serpin A1 in the early diagnosis of Parkinson’s disease dementia. PLoS One 7(11):e48783. https://doi.org/10.1371/journal.pone.0048783
Ji LJ, Shi J, Lu JM, Huang QM (2018) MiR-150 alleviates neuropathic pain via inhibiting toll-like receptor 5. J Cell Biochem 119(1):1017–1026. https://doi.org/10.1002/jcb.26269
Ji N, Wang Y, Bao G, Yan J, Ji S (2019) LncRNA SNHG14 promotes the progression of cervical cancer by regulating miR-206/YWHAZ. Pathol Res Pract 215(4):668–675. https://doi.org/10.1016/j.prp.2018.12.026
Jiang H, Yu Y, Liu S, Zhu M, Dong X, Wu J, Zhang Z, Zhang M, Zhang Y (2019) Proteomic study of a Parkinson’s disease model of undifferentiated SH-SY5Y cells induced by a proteasome inhibitor. Int J Med Sci 16(1):84–92. https://doi.org/10.7150/ijms.28595
Joutsa J, Gardberg M, Röyttä M, Kaasinen V (2014) Diagnostic accuracy of Parkinsonism syndromes by general neurologists. Parkinsonism Relat Disord 20(8):840–844. https://doi.org/10.1016/j.parkreldis.2014.04.019
Kelly J, Moyeed R, Carroll C, Albani D, Li X (2019) Gene expression meta-analysis of Parkinson’s disease and its relationship with Alzheimer’s disease. Mol Brain 12(1):16. https://doi.org/10.1186/s13041-019-0436-5
Kim SI, Voshol H, van Oostrum J, Hastings TG, Cascio M, Glucksman MJ (2004) Neuroproteomics: expression profiling of the brain’s proteomes in health and disease. Neurochem Res 29(6):1317–1331. https://doi.org/10.1023/b:nere.0000023618.35579.7c
Kulisevsky J, Oliveira L, Fox SH (2018) Update in therapeutic strategies for Parkinson’s disease. Curr Opin Neurol 31(4):439–447. https://doi.org/10.1097/wco.0000000000000579
Lau P, Bossers K, Janky R, Salta E, Frigerio CS, Barbash S, Rothman R, Sierksma AS, Thathiah A, Greenberg D, Papadopoulou AS, Achsel T, Ayoubi T, Soreq H, Verhaagen J, Swaab DF, Aerts S, De Strooper B (2013) Alteration of the microRNA network during the progression of Alzheimer’s disease. EMBO Mol Med 5(10):1613–1634. https://doi.org/10.1002/emmm.201201974
Li H, Yu L, Li M, Chen X, Tian Q, Jiang Y, Li N (2020) MicroRNA-150 serves as a diagnostic biomarker and is involved in the inflammatory pathogenesis of Parkinson’s disease. Mol Genet Genom Med 8(4):e1189. https://doi.org/10.1002/mgg3.1189
Lindholm D, Wootz H, Korhonen L (2006) ER stress and neurodegenerative diseases. Cell Death Differ 13(3):385–392. https://doi.org/10.1038/sj.cdd.4401778
Liu F, Di Wang X (2019) miR-150-5p represses TP53 tumor suppressor gene to promote proliferation of colon adenocarcinoma. Sci Rep 9(1):6740. https://doi.org/10.1038/s41598-019-43231-5
Lugli G, Cohen AM, Bennett DA, Shah RC, Fields CJ, Hernandez AG, Smalheiser NR (2015) Plasma exosomal miRNAs in Persons with and without Alzheimer disease: altered expression and prospects for biomarkers. PLoS One 10(10):e0139233. https://doi.org/10.1371/journal.pone.0139233
Meder D, Herz DM, Rowe JB, Lehéricy S, Siebner HR (2019) The role of dopamine in the brain—lessons learned from Parkinson’s disease. Neuroimage 190:79–93. https://doi.org/10.1016/j.neuroimage.2018.11.021
Mi H, Thomas P (2009) PANTHER pathway: an ontology-based pathway database coupled with data analysis tools. Methods Mol Biol (clifton, NJ) 563:123–140. https://doi.org/10.1007/978-1-60761-175-2_7
Miller DB, O’Callaghan JP (2015) Biomarkers of Parkinson’s disease: present and future. Metabolism 64(3 Suppl 1):S40-46. https://doi.org/10.1016/j.metabol.2014.10.030
Nielsen HM, Minthon L, Londos E, Blennow K, Miranda E, Perez J, Crowther DC, Lomas DA, Janciauskiene SM (2007) Plasma and CSF serpins in Alzheimer disease and dementia with Lewy bodies. Neurology 69(16):1569–1579. https://doi.org/10.1212/01.wnl.0000271077.82508.a0
Niu Y, Wan C, Zhang J, Zhang S, Zhao Z, Zhu L, Wang X, Ren X, Wang J, Lei P (2021) Aerobic exercise improves VCI through circRIMS2/miR-186/BDNF-mediated neuronal apoptosis. Mol Med (Cambridge, Mass) 27(1):4. https://doi.org/10.1186/s10020-020-00258-z
Ordonez DG, Lee MK, Feany MB (2018) α-synuclein Induces mitochondrial dysfunction through spectrin and the actin cytoskeleton. Neuron 97(1):108-124.e106. https://doi.org/10.1016/j.neuron.2017.11.036
Orosz F, Oláh J, Ovádi J (2009) Triosephosphate isomerase deficiency: new insights into an enigmatic disease. Biochem Biophys Acta 1792(12):1168–1174. https://doi.org/10.1016/j.bbadis.2009.09.012
Ozdilek B, Demircan B (2020) Serum microRNA expression levels in Turkish patients with Parkinson’s disease. Int J Neurosci. https://doi.org/10.1080/00207454.2020.1784165
Pandey A, Jauhari A, Singh T, Singh P, Singh N, Srivastava AK, Khan F, Pant AB, Parmar D, Yadav S (2015) Transactivation of P53 by cypermethrin induced miR-200 and apoptosis in neuronal cells. Toxicol Res 4(6):1578–1586
Pandey A, Singh P, Jauhari A, Singh T, Khan F, Pant AB, Parmar D, Yadav S (2015b) Critical role of the miR-200 family in regulating differentiation and proliferation of neurons. J Neurochem 133(5):640–652. https://doi.org/10.1111/jnc.13089
Pandey A, Sarkar S, Yadav SK, Yadav SS, Srikrishna S, Siddiqui MH, Parmar D, Yadav S (2022) Studies on regulation of global protein profile and cellular bioenergetics of differentiating SH-SY5Y cells. Mol Neurobiol. https://doi.org/10.1007/s12035-021-02667-5
Parisi C, Arisi I, D’Ambrosi N, Storti AE, Brandi R, D’Onofrio M, Volonté C (2013) Dysregulated microRNAs in amyotrophic lateral sclerosis microglia modulate genes linked to neuroinflammation. Cell Death Dis 4(12):e959. https://doi.org/10.1038/cddis.2013.491
Parnetti L, Gaetani L, Eusebi P, Paciotti S, Hansson O, El-Agnaf O, Mollenhauer B, Blennow K, Calabresi P (2019) CSF and blood biomarkers for Parkinson’s disease. Lancet Neurol 18(6):573–586. https://doi.org/10.1016/s1474-4422(19)30024-9
Peters M, Fitzpatrick R, Doll H, Playford D, Jenkinson C (2011) Does self-reported well-being of patients with Parkinson’s disease influence caregiver strain and quality of life? Parkinsonism Relat Disord 17(5):348–352. https://doi.org/10.1016/j.parkreldis.2011.02.009
Pienaar IS, Daniels WM, Götz J (2008) Neuroproteomics as a promising tool in Parkinson’s disease research. J Neural Transmission (Vienna, Austria: 1996) 115(10):1413–1430. https://doi.org/10.1007/s00702-008-0070-3
Puchades M, Hansson SF, Nilsson CL, Andreasen N, Blennow K, Davidsson P (2003) Proteomic studies of potential cerebrospinal fluid protein markers for Alzheimer’s disease. Brain Res Mol Brain Res 118(1–2):140–146. https://doi.org/10.1016/j.molbrainres.2003.08.005
Qiu F, Sun R, Deng N, Guo T, Cao Y, Yu Y, Wang X, Zou B, Zhang S, Jing T, Ling T, Xie J, Zhang Q (2015) miR-29a/b enhances cell migration and invasion in nasopharyngeal carcinoma progression by regulating SPARC and COL3A1 gene expression. PloS One 10(3):e0120969. https://doi.org/10.1371/journal.pone.0120969
Rao S, Oyang L, Liang J, Yi P, Han Y, Luo X, Xia L, Lin J, Tan S, Hu J, Wang H, Tang L, Pan Q, Tang Y, Zhou Y, Liao Q (2021) Biological function of HYOU1 in tumors and other diseases. Onco Targets Ther 14:1727–1735. https://doi.org/10.2147/ott.S297332
Satoh J, Kino Y, Niida S (2015) MicroRNA-seq data analysis pipeline to identify blood biomarkers for Alzheimer’s disease from public data. Biomarker Insights 10:21–31. https://doi.org/10.4137/bmi.S25132
Serafin A, Foco L, Blankenburg H, Picard A, Zanigni S, Zanon A, Pramstaller PP, Hicks AA, Schwienbacher C (2014) Identification of a set of endogenous reference genes for miRNA expression studies in Parkinson’s disease blood samples. BMC Res Notes 7:715. https://doi.org/10.1186/1756-0500-7-715
Singh S, Dikshit M (2007) Apoptotic neuronal death in Parkinson’s disease: involvement of nitric oxide. Brain Res Rev 54(2):233–250. https://doi.org/10.1016/j.brainresrev.2007.02.001
Srivastava AK, Yadav SS, Mishra S, Yadav SK, Parmar D, Yadav S (2020) A combined microRNA and proteome profiling to investigate the effect of ZnO nanoparticles on neuronal cells. Nanotoxicology 14(6):757–773. https://doi.org/10.1080/17435390.2020.1759726
Sun C, Jia N, Li R, Zhang Z, Zhong Y, Han K (2020) miR-143-3p inhibition promotes neuronal survival in an Alzheimer’s disease cell model by targeting neuregulin-1. Folia Neuropathol 58(1):10–21. https://doi.org/10.5114/fn.2020.94002
Sveinbjornsdottir S (2016) The clinical symptoms of Parkinson’s disease. J Neurochem 139(Suppl 1):318–324. https://doi.org/10.1111/jnc.13691
Swahari V, Nakamura A, Hollville E, Stroud H, Simon JM, Ptacek TS, Beck MV, Flowers C, Guo J, Plestant C, Liang J, Kurtz CL, Kanke M, Hammond SM, He YW, Anton ES, Sethupathy P, Moy SS, Greenberg ME, Deshmukh M (2021) MicroRNA-29 is an essential regulator of brain maturation through regulation of CH methylation. Cell Rep 35(1):108946. https://doi.org/10.1016/j.celrep.2021.108946
Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P, Jensen LJ, Mering CV (2019) STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 47(D1):D607-d613. https://doi.org/10.1093/nar/gky1131
Tatura R, Kraus T, Giese A, Arzberger T, Buchholz M, Höglinger G, Müller U (2016) Parkinson’s disease: SNCA-, PARK2-, and LRRK2- targeting microRNAs elevated in cingulate gyrus. Parkinsonism Relat Disord 33:115–121. https://doi.org/10.1016/j.parkreldis.2016.09.028
Tufekci KU, Alural B, Tarakcioglu E, San T, Genc S (2021) Lithium inhibits oxidative stress-induced neuronal senescence through miR-34a. Mol Biol Rep 48(5):4171–4180. https://doi.org/10.1007/s11033-021-06430-w
Tysnes OB, Storstein A (2017) Epidemiology of Parkinson’s disease. J Neural Transmission (Vienna, Austria: 1996) 124(8):901–905. https://doi.org/10.1007/s00702-017-1686-y
Vila M, Jackson-Lewis V, Vukosavic S, Djaldetti R, Liberatore G, Offen D, Korsmeyer SJ, Przedborski S (2001) Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Proc Natl Acad Sci USA 98(5):2837–2842. https://doi.org/10.1073/pnas.051633998
Vlachos IS, Zagganas K, Paraskevopoulou MD, Georgakilas G, Karagkouni D, Vergoulis T, Dalamagas T, Hatzigeorgiou AG (2015) DIANA-miRPath v3.0: deciphering microRNA function with experimental support. Nucleic Acids Res 43(W1):W460-466. https://doi.org/10.1093/nar/gkv403
Wang J, Lou H, Pedersen CJ, Smith AD, Perez RG (2009) 14–3-3zeta contributes to tyrosine hydroxylase activity in MN9D cells: localization of dopamine regulatory proteins to mitochondria. J Biol Chem 284(21):14011–14019. https://doi.org/10.1074/jbc.M901310200
Wang Y, Yang Z, Le W (2017) Tiny but mighty: promising roles of micrornas in the diagnosis and treatment of Parkinson’s disease. Neurosci Bull 33(5):543–551. https://doi.org/10.1007/s12264-017-0160-z
Wang R, Bao H, Zhang S, Li R, Chen L, Zhu Y (2018) miR-186-5p promotes apoptosis by targeting IGF-1 in SH-SY5Y OGD/R model. Int J Biol Sci 14(13):1791–1799. https://doi.org/10.7150/ijbs.25352
Wang C, Jia Q, Guo X, Li K, Chen W, Shen Q, Xu C, Fu Y (2022) microRNA-34 family: from mechanism to potential applications. Int J Biochem Cell Biol 144:106168. https://doi.org/10.1016/j.biocel.2022.106168
Warner TT, Schapira AH (2003) Genetic and environmental factors in the cause of Parkinson’s disease. Ann Neurol 53(3):S16-23. https://doi.org/10.1002/ana.10487
Wen JY, Chen G, Li JD, Luo JY, He J, Wang RS, Qin LT (2022) Downregulated miR-150-5p in the tissue of nasopharyngeal carcinoma. Genet Res 2022:2485055. https://doi.org/10.1155/2022/2485055
Xiong N, Xiong J, Jia M, Liu L, Zhang X, Chen Z, Huang J, Zhang Z, Hou L, Luo Z, Ghoorah D, Lin Z, Wang T (2013) The role of autophagy in Parkinson’s disease: rotenone-based modeling. Behav Brain Funct 9:13. https://doi.org/10.1186/1744-9081-9-13
Xu J, Kao SY, Lee FJ, Song W, Jin LW, Yankner BA (2002) Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nat Med 8(6):600–606. https://doi.org/10.1038/nm0602-600
Xu YF, Liu J, Wang J, Guo YC, Shen YZ (2020) MiR-186 promotes the apoptosis of glioma U87 cells by down-regulating the expression of Smad6. Eur Rev Med Pharmacol Sci 24(14):7681–7689. https://doi.org/10.26355/eurrev_202007_22269
Yadav S, Pandey A, Shukla A, Talwelkar SS, Kumar A, Pant AB, Parmar D (2011) miR-497 and miR-302b regulate ethanol-induced neuronal cell death through BCL2 protein and cyclin D2. J Biol Chem 286(43):37347–37357. https://doi.org/10.1074/jbc.M111.235531
Yadav S, Jauhari A, Singh N, Singh T, Srivastav AK, Singh P, Pant A, Parmar D (2015) MicroRNAs are emerging as most potential molecular biomarkers. Biochem Anal Biochem. https://doi.org/10.4172/2161-1009.1000191
Yadav SK, Pandey A, Sarkar S, Yadav SS, Parmar D, Yadav S (2022) Identification of altered blood microRNAs and plasma proteins in a rat model of Parkinson’s disease. Mol Neurobiol. https://doi.org/10.1007/s12035-021-02636-y
Yaduvanshi S, Ero R, Kumar V (2021) The mechanism of complex formation between calmodulin and voltage gated calcium channels revealed by molecular dynamics. PloS one 16(10):e0258112. https://doi.org/10.1371/journal.pone.0258112
Yuan J, Yankner BA (2000) Apoptosis in the nervous system. Nature 407(6805):802–809. https://doi.org/10.1038/35037739
Yuan Q, Zhang S, Li J, Xiao J, Li X, Yang J, Lu D, Wang Y (2020) Comprehensive analysis of core genes and key pathways in Parkinson’s disease. Am J Transl Res 12(9):5630–5639
Zhang F, Wang D (2017) The pattern of microRNA binding site distribution. Genes. https://doi.org/10.3390/genes8110296
Zhang S, Jin J, Tian X, Wu L (2017) hsa-miR-29c-3p regulates biological function of colorectal cancer by targeting SPARC. Oncotarget 8(61):104508–104524. https://doi.org/10.18632/oncotarget.22356
Zhou T, Huang Z, Zhu X, Sun X, Liu Y, Cheng B, Li M, Liu Y, He C, Liu X (2018) Alpha-1 antitrypsin attenuates M1 microglia-mediated neuroinflammation in retinal degeneration. Front Immunol 9:1202. https://doi.org/10.3389/fimmu.2018.01202
Zhu XG, Zhang TN, Wen R, Liu CF (2020) Overexpression of miR-150-5p alleviates apoptosis in sepsis-induced myocardial depression. Biomed Res Int 2020:3023186. https://doi.org/10.1155/2020/3023186
Acknowledgements
Dr Sanjeev Kumar Yadav is grateful to CSIR, New Delhi, for providing JRF/SRF fellowship. We also thank Dr VK Khanna for the valuable suggestions. The CSIR-IITR communication reference number is IITR/SEC/MS/2023/01.
Funding
The funding for the present study has been provided by the CSIR Network project (miND) and Science and Engineering Research Board (SERB), New Delhi project (GAP-359; Grant Sanction no. EMR/2016/002965).
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SY, DP, RKG, and SP designed the study. SY guided the students in the protocols and new methods development. SKY, AJ, and NS performed the experiments. SKY collated the data, performed the data analysis, and write the first draft of the manuscript. AP and SS provided the technical assistance for the data analysis. All the authors reviewed and gave critical suggestions and approved the manuscript.
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The study was approved by the Institutional Ethics committee of King George’s Medical University (KGMU) U.P., India (Ref. code: 89th ECM II A/P7) and the Institutional Human Ethics Committee of Indian Institute of Toxicology Research (IITR) U.P., India (Ref. No: CSIR-IITR/IHEC/JULY/2021/2).
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Yadav, S.K., Jauhari, A., Singh, N. et al. Transcriptomics and Proteomics Approach for the Identification of Altered Blood microRNAs and Plasma Proteins in Parkinson’s Disease. Cell Mol Neurobiol 43, 3527–3553 (2023). https://doi.org/10.1007/s10571-023-01362-4
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DOI: https://doi.org/10.1007/s10571-023-01362-4