Identification of metabolic pathways and key genes associated with atypical parkinsonism using a systems biology approach.
And Lewy body dementia
Atypical parkinsonism
Corticobasal degeneration
Multiple system atrophy
Progressive supranuclear palsy
Systems biology
Journal
Metabolic brain disease
ISSN: 1573-7365
Titre abrégé: Metab Brain Dis
Pays: United States
ID NLM: 8610370
Informations de publication
Date de publication:
02 Feb 2024
02 Feb 2024
Historique:
received:
06
06
2023
accepted:
23
12
2023
medline:
2
2
2024
pubmed:
2
2
2024
entrez:
2
2
2024
Statut:
aheadofprint
Résumé
Atypical parkinsonism (AP) is a group of complex neurodegenerative disorders with marked clinical and pathophysiological heterogeneity. The use of systems biology tools may contribute to the characterization of hub-bottleneck genes, and the identification of its biological pathways to broaden the understanding of the bases of these disorders. A systematic search was performed on the DisGeNET database, which integrates data from expert curated repositories, GWAS catalogues, animal models and the scientific literature. The tools STRING 11.0 and Cytoscape 3.8.2 were used for analysis of protein-protein interaction (PPI) network. The PPI network topography analyses were performed using the CytoHubba 0.1 plugin for Cytoscape. The hub and bottleneck genes were inserted into 4 different sets on the InteractiveVenn. Additional functional enrichment analyses were performed to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology for a described set of genes. The systematic search in the DisGeNET database identified 485 genes involved with Atypical Parkinsonism. Superimposing these genes, we detected a total of 31 hub-bottleneck genes. Moreover, our functional enrichment analyses demonstrated the involvement of these hub-bottleneck genes in 3 major KEGG pathways. We identified 31 highly interconnected hub-bottleneck genes through a systems biology approach, which may play a key role in the pathogenesis of atypical parkinsonism. The functional enrichment analyses showed that these genes are involved in several biological processes and pathways, such as the glial cell development, glial cell activation and cognition, pathways were related to Alzheimer disease and Parkinson disease. As a hypothesis, we highlight as possible key genes for AP the MAPT (microtubule associated protein tau), APOE (apolipoprotein E), SNCA (synuclein alpha) and APP (amyloid beta precursor protein) genes.
Identifiants
pubmed: 38305999
doi: 10.1007/s11011-024-01342-7
pii: 10.1007/s11011-024-01342-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
ID : Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Allen SJ, Watson JJ, Shoemark DK et al (2013) GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol Ther 138:155–175. https://doi.org/10.1016/j.pharmthera.2013.01.004
doi: 10.1016/j.pharmthera.2013.01.004
pubmed: 23348013
Arendt T, Stieler JT, Holzer M (2016) Tau and tauopathies. Brain Res Bull 126:238–292. https://doi.org/10.1016/j.brainresbull.2016.08.018
doi: 10.1016/j.brainresbull.2016.08.018
pubmed: 27615390
Aydin D, Weyer SW, Müller UC (2012) Functions of the APP gene family in the nervous system: insights from mouse models. Exp Brain Res 217:423–434. https://doi.org/10.1007/s00221-011-2861-2
doi: 10.1007/s00221-011-2861-2
pubmed: 21931985
Bindea G, Mlecnik B, Hackl H et al (2009) ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 25:1091–1093. https://doi.org/10.1093/bioinformatics/btp101
doi: 10.1093/bioinformatics/btp101
pubmed: 19237447
pmcid: 2666812
Booth HDE, Hirst WD, Wade-Martins R (2017) The role of astrocyte dysfunction in Parkinson’s Disease Pathogenesis. Trends Neurosci 40:358–370. https://doi.org/10.1016/j.tins.2017.04.001
doi: 10.1016/j.tins.2017.04.001
pubmed: 28527591
pmcid: 5462417
Bras J, Guerreiro R, Darwent L et al (2014) Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies. Hum Mol Genet 23:6139–6146. https://doi.org/10.1093/hmg/ddu334
doi: 10.1093/hmg/ddu334
pubmed: 24973356
pmcid: 4222357
Brown RC, Lockwood AH, Sonawane BR (2005) Neurodegenerative diseases: an overview of environmental risk factors. Environ Health Perspect 113:1250–1256. https://doi.org/10.1289/ehp.7567
doi: 10.1289/ehp.7567
pubmed: 16140637
pmcid: 1280411
Caillet-Boudin ML, Buée L, Sergeant N, Lefebvre B (2015) Regulation of human MAPT gene expression. Mol Neurodegener 10:1–14. https://doi.org/10.1186/s13024-015-0025-8
doi: 10.1186/s13024-015-0025-8
Chen Y, Cao B, Yang J et al (2015) Analysis and meta-analysis of five polymorphisms of the LINGO1 and LINGO2 genes in Parkinson’s disease and multiple system atrophy in a Chinese population. J Neurol 262:2478–2483. https://doi.org/10.1007/s00415-015-7870-9
doi: 10.1007/s00415-015-7870-9
pubmed: 26254004
Chia R, Sabir MS, Bandres-Ciga S et al (2021) Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture. Nat Genet 53:294–303. https://doi.org/10.1038/s41588-021-00785-3
doi: 10.1038/s41588-021-00785-3
pubmed: 33589841
pmcid: 7946812
Dai L, Zou L, Meng L et al (2021) Cholesterol metabolism in neurodegenerative diseases: Molecular mechanisms and therapeutic targets. Mol Neurobiol 58:2183–2201. https://doi.org/10.1007/s12035-020-02232-6
doi: 10.1007/s12035-020-02232-6
pubmed: 33411241
Deutschländer AB, Ross OA, Dickson DW, Wszolek ZK (2018) Atypical parkinsonian syndromes: a general neurologist’s perspective. Eur J Neurol
Devi G (2023) The tauopathies. Handb Clin Neurol 196:251–265. https://doi.org/10.1016/B978-0-323-98817-9.00015-6
doi: 10.1016/B978-0-323-98817-9.00015-6
pubmed: 37620072
Dickson DW, Bergeron C, Chin SS et al (2002) Office of rare diseases neuropathologic criteria for corticobasal degeneration. J Neuropathol Exp Neurol 61. https://doi.org/10.1093/jnen/61.11.935
Dietschy JM, Turley SD (2004) Cholesterol metabolism in the central nervous system during early development and in the mature animal. J Lipid Res
Diez-Fairen M, Alvarez Jerez P, Berghausen J, Bandres-Ciga S (2021) The Genetic Landscape of parkinsonism-related Dystonias and atypical parkinsonism-related syndromes. Int J Mol Sci 22. https://doi.org/10.3390/ijms22158100
Don AS, Hsiao J-HT, Bleasel JM et al (2014) Altered lipid levels provide evidence for myelin dysfunction in multiple system atrophy. Acta Neuropathol Commun 2:150. https://doi.org/10.1186/s40478-014-0150-6
doi: 10.1186/s40478-014-0150-6
pubmed: 25358962
pmcid: 4228091
Fabbrini G, Fabbrini A, Suppa A (2019) Progressive supranuclear palsy, multiple system atrophy and corticobasal degeneration. Handb Clin Neurol 165:155–177. https://doi.org/10.1016/B978-0-444-64012-3.00009-5
doi: 10.1016/B978-0-444-64012-3.00009-5
pubmed: 31727210
Fellner L, Stefanova N (2013) The role of glia in α-synucleinopathies. Mol Neurobiol 47:575–586. https://doi.org/10.1007/s12035-012-8340-3
doi: 10.1007/s12035-012-8340-3
pubmed: 22941028
Foguem C, Manckoundia P (2018) Lewy Body Disease: clinical and pathological overlap syndrome between synucleinopathies (Parkinson Disease) and tauopathies (Alzheimer Disease). Curr Neurol Neurosci Rep 18
Giagkou N, Stamelou M (2018) Therapeutic management of the overlapping syndromes of atypical parkinsonism. CNS Drugs
Harris MA, Clark JI, Ireland A et al (2006) The gene ontology (GO) project in 2006. Nucleic Acids Res 34:D322–D326. https://doi.org/10.1093/nar/gkj021
doi: 10.1093/nar/gkj021
Heberle H, Meirelles VG, da Silva FR et al (2015) InteractiVenn: a web-based tool for the analysis of sets through Venn diagrams. BMC Bioinformatics 16:1–7. https://doi.org/10.1186/s12859-015-0611-3
doi: 10.1186/s12859-015-0611-3
Heckman MG, Kasanuki K, Brennan RR et al (2019) Association of MAPT H1 subhaplotypes with neuropathology of lewy body disease. Mov Disord 34:1325–1332. https://doi.org/10.1002/mds.27773
doi: 10.1002/mds.27773
pubmed: 31234228
pmcid: 7996001
Höglinger GU, Melhem NM, Dickson DW et al (2011) Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat Genet 43:699–705. https://doi.org/10.1038/ng.859
doi: 10.1038/ng.859
pubmed: 21685912
pmcid: 3125476
Höglinger GU, Respondek G, Stamelou M et al (2017) Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Mov Disord. https://doi.org/10.1002/mds.26987
doi: 10.1002/mds.26987
pubmed: 28590575
pmcid: 5543934
Holmberg B, Rosengren L, Karlsson J-E, Johnels B (1998) Increased cerebrospinal fluid levels of neurofilament protein in progressive supranuclear palsy and multiple-system atrophy compared with Parkinson’s disease. Mov Disord 13:70–77. https://doi.org/10.1002/mds.870130116
doi: 10.1002/mds.870130116
pubmed: 9452329
Jellinger KA (2018) Multiple system atrophy: an oligodendroglioneural Synucleinopathy1. J Alzheimers Dis 62:1141–1179. https://doi.org/10.3233/JAD-170397
doi: 10.3233/JAD-170397
pubmed: 28984582
pmcid: 5870010
Jellinger KA, Wenning GK (2016) Multiple system atrophy: pathogenic mechanisms and biomarkers. J Neural Transm (Vienna) 123:555–572. https://doi.org/10.1007/s00702-016-1545-2
doi: 10.1007/s00702-016-1545-2
pubmed: 27098666
Kim EK, Choi EJ (2010) Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta Mol Basis Dis 1802:396–405. https://doi.org/10.1016/j.bbadis.2009.12.009
doi: 10.1016/j.bbadis.2009.12.009
Kim SS, Moon KR, Choi HJ (2011) Interference of alpha-synuclein with cAMP/PKA-dependent CREB signaling for tyrosine hydroxylase gene expression in SK-N-BE(2)C cells. Arch Pharm Res 34:837–845. https://doi.org/10.1007/s12272-011-0518-0
doi: 10.1007/s12272-011-0518-0
pubmed: 21656370
Kouri N, Ross OA, Dombroski B et al (2015) Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy. Nat Commun 6:1–7. https://doi.org/10.1038/ncomms8247
doi: 10.1038/ncomms8247
Lill CM (2016) Genetics of Parkinson’s disease. Mol Cell Probes
Lim Y, Kehm VM, Lee EB et al (2011) Α-Syn suppression reverses synaptic and memory defects in a mouse model of Dementia with Lewy Bodies. J Neurosci 31:10076–10087. https://doi.org/10.1523/JNEUROSCI.0618-11.2011
doi: 10.1523/JNEUROSCI.0618-11.2011
pubmed: 21734300
pmcid: 3144489
Lim EW, Aarsland D, Ffytche D et al (2019) Amyloid-β and Parkinson’s disease. J Neurol 266:2605–2619. https://doi.org/10.1007/s00415-018-9100-8
doi: 10.1007/s00415-018-9100-8
pubmed: 30377818
McKeith IG, Boeve BF, Dickson DW et al (2017) Diagnosis and management of dementia with Lewy bodies. Neurology 89:88–100. https://doi.org/10.1212/WNL.0000000000004058
Melissa J, Armstrong et al (2013) Criteria for the diagnosis of corticobasal degeneration. Neurology 67:513–523. https://doi.org/10.1212/WNL.0b013e31827f0fd1 .
doi: 10.1212/WNL.0b013e31827f0fd1
Minoru Kanehisa and Susumu Goto (2000) KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28:27–30
doi: 10.1093/nar/28.1.27
Miryala SK, Anbarasu A, Ramaiah S (2018) Discerning molecular interactions: A comprehensive review on biomolecular interaction databases and network analysis tools. Gene
Mitsui J, Matsukawa T, Sasaki H et al (2015) Variants associated with gaucher disease in multiple system atrophy. Ann Clin Transl Neurol. https://doi.org/10.1002/acn3.185
doi: 10.1002/acn3.185
pubmed: 25909086
pmcid: 4402086
Pang E, Hao Y, Sun Y, Lin K (2016) Differential variation patterns between hubs and bottlenecks in human protein-protein interaction networks. BMC Evol Biol. https://doi.org/10.1186/s12862-016-0840-8
doi: 10.1186/s12862-016-0840-8
pubmed: 27903259
pmcid: 5131443
Piñero J, Bravo Á, Queralt-Rosinach N et al (2017a) DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res 45:D833–D839. https://doi.org/10.1093/nar/gkw943
doi: 10.1093/nar/gkw943
pubmed: 27924018
Piñero J, Bravo Á, Queralt-Rosinach N et al (2017b) DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res. https://doi.org/10.1093/nar/gkw943
doi: 10.1093/nar/gkw943
pubmed: 27924018
Polymeropoulos MH, Lavedan C, Leroy E et al (1997) Mutation in the α-synuclein gene identified in families with Parkinson’s disease. Sci (1979) 276:2045–2047. https://doi.org/10.1126/science.276.5321.2045
Povey S, Lovering R, Bruford E et al (2001) The HUGO Gene Nomenclature Committee (HGNC). Hum Genet 109:678–680. https://doi.org/10.1007/s00439-001-0615-0
doi: 10.1007/s00439-001-0615-0
pubmed: 11810281
Rahmati S, Abovsky M, Pastrello C, Jurisica I (2017) PathDIP: an annotated resource for known and predicted human gene-pathway associations and pathway enrichment analysis. Nucleic Acids Res 45:D419–D426. https://doi.org/10.1093/nar/gkw1082
doi: 10.1093/nar/gkw1082
pubmed: 27899558
Rösler TW, Tayaranian Marvian A, Brendel M et al (2019) Four-repeat tauopathies. Prog Neurobiol 180:101644. https://doi.org/10.1016/j.pneurobio.2019.101644
doi: 10.1016/j.pneurobio.2019.101644
pubmed: 31238088
Sabir MS, Blauwendraat C, Ahmed S et al (2019) Assessment of APOE in atypical parkinsonism syndromes. Neurobiol Dis 127:142–146. https://doi.org/10.1016/j.nbd.2019.02.016
doi: 10.1016/j.nbd.2019.02.016
pubmed: 30798004
pmcid: 6588472
Sanford AM (2018) Lewy Body Dementia. Clin Geriatr Med 34:603–615. https://doi.org/10.1016/j.cger.2018.06.007
doi: 10.1016/j.cger.2018.06.007
pubmed: 30336990
Sawa A, Amano N, Yamada N et al (1997) Apolipoprotein E in progressive supranuclear palsy in Japan. Mol Psychiatry 2:341–342. https://doi.org/10.1038/sj.mp.4000285
doi: 10.1038/sj.mp.4000285
pubmed: 9246676
Scholz SW, Bras J (2015) Genetics underlying atypical parkinsonism and related neurodegenerative disorders. Int J Mol Sci
Scholz SW, Houlden H, Schulte C et al (2009) SNCA variants are associated with increased risk for multiple system atrophy. Ann Neurol 65:610–614. https://doi.org/10.1002/ana.21685
doi: 10.1002/ana.21685
pubmed: 19475667
pmcid: 3520128
Serrano-Pozo A, Das S, Hyman BT (2021) APOE and Alzheimer’s disease: advances in genetics, pathophysiology, and therapeutic approaches. Lancet Neurol 20:68–80. https://doi.org/10.1016/S1474-4422(20)30412-9
doi: 10.1016/S1474-4422(20)30412-9
pubmed: 33340485
pmcid: 8096522
Shannon P, Markiel A, Ozier O et al (2003) Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504. https://doi.org/10.1101/gr.1239303
doi: 10.1101/gr.1239303
pubmed: 14597658
pmcid: 403769
Sidransky E, Nalls MA, Aasly JO et al (2009) Multicenter Analysis of glucocerebrosidase mutations in Parkinson’s Disease. N Engl J Med. https://doi.org/10.1056/NEJMoa0901281
doi: 10.1056/NEJMoa0901281
pubmed: 19846850
pmcid: 2856322
Stamelou M, Respondek G, Giagkou N et al (2021) Evolving concepts in progressive supranuclear palsy and other 4-repeat tauopathies. Nat Rev Neurol 17:601–620. https://doi.org/10.1038/s41582-021-00541-5
doi: 10.1038/s41582-021-00541-5
pubmed: 34426686
Stefanis L (2012) α-Synuclein in Parkinson’s disease. Cold Spring Harb Perspect Med 2:a009399. https://doi.org/10.1101/cshperspect.a009399
doi: 10.1101/cshperspect.a009399
pubmed: 22355802
pmcid: 3281589
Stefanova N, Reindl M, Neumann M et al (2007) Microglial activation mediates neurodegeneration related to oligodendroglial alpha-synucleinopathy: implications for multiple system atrophy. Mov Disord 22:2196–2203. https://doi.org/10.1002/mds.21671
doi: 10.1002/mds.21671
pubmed: 17853477
Strang KH, Golde TE, Giasson BI (2019) MAPT mutations, tauopathy, and mechanisms of neurodegeneration. Lab Invest 99:912–928. https://doi.org/10.1038/s41374-019-0197-x
doi: 10.1038/s41374-019-0197-x
pubmed: 30742061
pmcid: 7289372
Szklarczyk D, Gable AL, Lyon D et al (2019) STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 47:D607–D613. https://doi.org/10.1093/nar/gky1131
doi: 10.1093/nar/gky1131
pubmed: 30476243
Tavassoly I, Goldfarb J, Iyengar R (2018) Systems biology primer: the basic methods and approaches. Essays Biochem 62:487–500. https://doi.org/10.1042/EBC20180003
doi: 10.1042/EBC20180003
pubmed: 30287586
Ubhi K, Lee PH, Adame A et al (2009) Mitochondrial inhibitor 3-nitroproprionic acid enhances oxidative modification of alpha-synuclein in a transgenic mouse model of multiple system atrophy. J Neurosci Res 87:2728–2739. https://doi.org/10.1002/jnr.22089
doi: 10.1002/jnr.22089
pubmed: 19405128
pmcid: 2885901
Vance JE (2012) Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases. DMM Disease Models and Mechanisms
Vidal M (2009) A unifying view of 21st century systems biology. FEBS Lett
Wenning GK, Stankovic I, Vignatelli L et al (2022) The Movement Disorder Society Criteria for the diagnosis of multiple system atrophy. Mov Disord 37:1131–1148
doi: 10.1002/mds.29005
pubmed: 35445419
pmcid: 9321158
Xu W, Tan L, Yu JT (2015) The link between the SNCA gene and parkinsonism. Neurobiol Aging 36:1505–1518. https://doi.org/10.1016/j.neurobiolaging.2014.10.042
doi: 10.1016/j.neurobiolaging.2014.10.042
pubmed: 25554495
Zhao N, Liu C-C, Van Ingelgom AJ et al (2018) APOE ε2 is associated with increased tau pathology in primary tauopathy. Nat Commun 9:4388. https://doi.org/10.1038/s41467-018-06783-0
doi: 10.1038/s41467-018-06783-0
pubmed: 30348994
pmcid: 6197187