Gene Expression Analysis of Laser-Captured Purkinje Cells in the Essential Tremor Cerebellum.
Essential tremor
Laser capture microdissection
Purkinje cell
RNA-sequencing
Journal
Cerebellum (London, England)
ISSN: 1473-4230
Titre abrégé: Cerebellum
Pays: United States
ID NLM: 101089443
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
accepted:
28
09
2022
pmc-release:
15
04
2024
medline:
20
11
2023
pubmed:
16
10
2022
entrez:
15
10
2022
Statut:
ppublish
Résumé
Essential tremor (ET) is a common, progressive neurological disease characterized by an 8-12-Hz kinetic tremor. Despite its high prevalence, the patho-mechanisms of tremor in ET are not fully known. Through comprehensive studies in postmortem brains, we identified major morphological changes in the ET cerebellum that reflect cellular damage in Purkinje cells (PCs), suggesting that PC damage is central to ET pathogenesis. We previously performed a transcriptome analysis in ET cerebellar cortex, identifying candidate genes and several dysregulated pathways. To directly target PCs, we purified RNA from PCs isolated by laser capture microdissection and performed the first ever PC-specific RNA-sequencing analysis in ET versus controls. Frozen postmortem cerebellar cortex from 24 ETs and 16 controls underwent laser capture microdissection, obtaining ≥2000 PCs per sample. RNA transcriptome was analyzed via differential gene expression, principal component analysis (PCA), and gene set enrichment analyses (GSEA). We identified 36 differentially expressed genes, encompassing multiple cellular processes. Some ET (13/24) had greater dysregulation of these genes and segregated from most controls and remaining ETs in PCA. Characterization of genes/pathways enriched in this PCA and GSEA identified multiple pathway dysregulations in ET, including RNA processing/splicing, synapse organization/ion transport, and oxidative stress/inflammation. Furthermore, a different set of pathways characterized marked heterogeneity among ET patients. Our data indicate a range of possible mechanisms for the pathogenesis of ET. Significant heterogeneity among ET combined with dysregulation of multiple cellular processes supports the notion that ET is a family of disorders rather than one disease entity.
Identifiants
pubmed: 36242761
doi: 10.1007/s12311-022-01483-4
pii: 10.1007/s12311-022-01483-4
pmc: PMC10359949
mid: NIHMS1917221
doi:
Substances chimiques
RNA
63231-63-0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1166-1181Subventions
Organisme : NINDS NIH HHS
ID : R01 NS088257
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS117745
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS124854
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS104423
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH103517
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS088257-01A1
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS094607
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS077094
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG011641
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS118179
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS086736
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Louis ED, McCreary M. How common is essential tremor? Update on the worldwide prevalence of essential tremor. Tremor Other Hyperkinet Mov. 2021;11(28). https://doi.org/10.5334/tohm.632 .
Clark LN, Louis ED. Essential tremor. Handb Clin Neurol. 2018;147:229–39. https://doi.org/10.1016/B978-0-444-63233-3.00015-4 .
doi: 10.1016/B978-0-444-63233-3.00015-4
pubmed: 29325613
pmcid: 5898616
Odgerel Z, Hernandez N, Park J, et al. Whole genome sequencing and rare variant analysis in essential tremor families. PLoS One. 2019;14(8):e0220512. https://doi.org/10.1371/journal.pone.0220512 .
doi: 10.1371/journal.pone.0220512
pubmed: 31404076
pmcid: 6690583
Liu X, Hernandez N, Kisselev S, et al. Identification of candidate genes for familial early-onset essential tremor. Eur J Hum Genet. 2016;24(7):1009–15. https://doi.org/10.1038/ejhg.2015.228 .
doi: 10.1038/ejhg.2015.228
pubmed: 26508575
Shatunov A, Sambuughin N, Jankovic J, et al. Genomewide scans in North American families reveal genetic linkage of essential tremor to a region on chromosome 6p23. Brain. 2006;129:2318–3. https://doi.org/10.1093/brain/awl120 .
doi: 10.1093/brain/awl120
pubmed: 16702189
Diez-Fairen M, Houle G, Ortega-Cubero S, et al. Exome-wide rare variant analysis in familial essential tremor. Parkinsonism Relat Disord. 2020;82:109–16. https://doi.org/10.1016/j.parkreldis.2020.11.021 .
doi: 10.1016/j.parkreldis.2020.11.021
pubmed: 33279834
pmcid: 7856267
Muller SH, Girard SL, Hopfner F, et al. Genome-wide association study in essential tremor identifies three new loci. Brain. 2016;139(Pt 12):3163–9. https://doi.org/10.1093/brain/aww242 .
doi: 10.1093/brain/aww242
pubmed: 27797806
pmcid: 5382938
Liao C, Castonguay C-E, Heilbron K, et al. Association of essential tremor with novel risk loci a genome-wide association study and meta-analysis. JAMA. Neurology. 2022. https://doi.org/10.1001/jamaneurol.2021.4781 .
Handforth A. Linking essential tremor to the cerebellum-animal model evidence. Cerebellum. 2016;15(3):285–98. https://doi.org/10.1007/s12311-015-0750-0 .
doi: 10.1007/s12311-015-0750-0
pubmed: 26660708
Pan MK, Li YS, Wong SB, et al. Cerebellar oscillations driven by synaptic pruning deficits of cerebellar climbing fibers contribute to tremor pathophysiology. Sci Transl Med. 2020;12(526):eaay1769. https://doi.org/10.1126/scitranslmed.aay1769 .
doi: 10.1126/scitranslmed.aay1769
pubmed: 31941824
pmcid: 7339589
Pan M-K, Ni C-L, Wu Y-C, Li Y-S, Kuo S-H. Animal models of tremor: relevance to human tremor disorders. Tremor Other Hyperkinet Mov. 2018;8(587):1–13. https://doi.org/10.7916/D89S37MV .
doi: 10.7916/D89S37MV
Louis ED, Jurewicz EC, Parides MK. Case-control study of nutritional antioxidant intake in essential tremor. Neuroepidemiology. 2005;24(4):203–8. https://doi.org/10.1159/000084713 .
doi: 10.1159/000084713
pubmed: 15802925
Miura S, Kamada T, Fujioka R, Yamanishi Y. Plasma amino acids in patients with essential tremor. Clin Case Rep. 2021;9(8):e04580. https://doi.org/10.1002/ccr3.4580 .
doi: 10.1002/ccr3.4580
pubmed: 34429988
pmcid: 8365401
Wong S-B, Wang Y-M, Lin C-C, et al. Cerebellar oscillations in familial and sporadic essential tremor. Cerebellum. 2021. https://doi.org/10.1007/s12311-021-01309-9 .
Kuo SH, Wang J, Tate WJ, et al. Cerebellar pathology in early onset and late onset essential tremor. Cerebellum. 2017;16(2):473–82. https://doi.org/10.1007/s12311-016-0826-5 .
doi: 10.1007/s12311-016-0826-5
pubmed: 27726094
pmcid: 5336493
Louis ED, Kuo S-H, Wang J, et al. Cerebellar pathology in familial vs. sporadic essential tremor. Cerebellum. 2017;16(4):786–91. https://doi.org/10.1007/s12311-017-0853-x .
doi: 10.1007/s12311-017-0853-x
pubmed: 28364185
pmcid: 6089244
Louis ED, Kerridge CA, Chatterjee D, et al. Contextualizing the pathology in the essential tremor cerebellar cortex: a patholog-omics approach. Acta Neuropathol. 2019;138(5):859–76. https://doi.org/10.1007/s00401-019-02043-7 .
doi: 10.1007/s00401-019-02043-7
pubmed: 31317229
pmcid: 7285399
Filip P, Lungu OV, Manto MU, Bares M. Linking essential tremor to the cerebellum: physiological evidence. Cerebellum. 2016;15(6):774–80. https://doi.org/10.1007/s12311-015-0740-2 .
doi: 10.1007/s12311-015-0740-2
pubmed: 26530223
Trujillo Diaz D, Hernandez NC, Cortes EP, et al. Banking brains: a pre-mortem “how to” guide to successful donation. Cell Tissue Bank. 2018;19(4):473–88. https://doi.org/10.1007/s10561-018-9720-3 .
doi: 10.1007/s10561-018-9720-3
pubmed: 30220002
Louis ED, Kuo SH, Vonsattel JP, Faust PL. Torpedo formation and Purkinje cell loss: modeling their relationship in cerebellar disease. Cerebellum. 2014;13(4):433–9. https://doi.org/10.1007/s12311-014-0556-5 .
doi: 10.1007/s12311-014-0556-5
pubmed: 24590661
pmcid: 4077970
Louis ED, Faust PL, Vonsattel JP, et al. Torpedoes in Parkinson's disease, Alzheimer's disease, essential tremor, and control brains. Mov Disord. 2009;24(11):1600–5. https://doi.org/10.1002/mds.22567 .
doi: 10.1002/mds.22567
pubmed: 19526585
pmcid: 2736313
Louis ED, Yi H, Erickson-Davis C, Vonsattel JP, Faust PL. Structural study of Purkinje cell axonal torpedoes in essential tremor. Neurosci Lett. 2009;450(3):287–91. https://doi.org/10.1016/j.neulet.2008.11.043 .
doi: 10.1016/j.neulet.2008.11.043
pubmed: 19047012
Babij R, Lee M, Cortes E, et al. Purkinje cell axonal anatomy: quantifying morphometric changes in essential tremor versus control brains. Brain. 2013;136(Pt 10):3051–61. https://doi.org/10.1093/brain/awt238 .
doi: 10.1093/brain/awt238
pubmed: 24030953
pmcid: 3784286
Yu M, Ma K, Faust PL, et al. Increased number of Purkinje cell dendritic swellings in essential tremor. Eur J Neurol. 2012;19(4):625–30. https://doi.org/10.1111/j.1468-1331.2011.03598.x .
doi: 10.1111/j.1468-1331.2011.03598.x
pubmed: 22136494
Louis ED, Lee M, Babij R, et al. Reduced Purkinje cell dendritic arborization and loss of dendritic spines in essential tremor. Brain. 2014;137(Pt 12):3142–8. https://doi.org/10.1093/brain/awu314 .
doi: 10.1093/brain/awu314
pubmed: 25367027
pmcid: 4240305
Choe M, Cortes E, Vonsattel JP, et al. Purkinje cell loss in essential tremor: random sampling quantification and nearest neighbor analysis. Mov Disord. 2016;31(3):393–401. https://doi.org/10.1002/mds.26490 .
doi: 10.1002/mds.26490
pubmed: 26861543
pmcid: 4783222
Louis ED, Kuo SH, Tate WJ, et al. Heterotopic Purkinje cells: a comparative postmortem study of essential tremor and spinocerebellar ataxias 1, 2, 3, and 6. Cerebellum. 2018;17(2):104–10. https://doi.org/10.1007/s12311-017-0876-3 .
doi: 10.1007/s12311-017-0876-3
pubmed: 28791574
pmcid: 5803474
Lee PJ, Kerridge CA, Chatterjee D, et al. A quantitative study of empty baskets in essential tremor and other motor neurodegenerative diseases. J Neuropathol Exp Neurol. 2018. https://doi.org/10.1093/jnen/nly114 .
Erickson-Davis CR, Faust PL, Vonsattel J-PG, et al. “Hairy baskets” associated with degenerative Purkinje cell changes in essential tremor. Neuropathol. Exp Neurol. 2010;69(3):262–71. https://doi.org/10.1097/NEN.0b013e3181d1ad04 .
doi: 10.1097/NEN.0b013e3181d1ad04
Lee D, Gan SR, Faust PL, Louis ED, Kuo SH. Climbing fiber-Purkinje cell synaptic pathology across essential tremor subtypes. Parkinsonism Relat Disord. 2018;51:24–9. https://doi.org/10.1016/j.parkreldis.2018.02.032 .
doi: 10.1016/j.parkreldis.2018.02.032
pubmed: 29482925
pmcid: 6089250
Lin C-Y, Louis ED, Faust PL, et al. Abnormal climbing fibre-Purkinje cell synaptic connections in the essential tremor cerebellum. Brain. 2014;137:3149–59. https://doi.org/10.1093/brain/awu281 .
doi: 10.1093/brain/awu281
pubmed: 25273997
pmcid: 4240294
Louis ED, Faust PL. Essential tremor pathology: neurodegeneration and reorganization of neuronal connections. Nat Rev Neurol. 2020;16(2):69–83. https://doi.org/10.1038/s41582-019-0302-1 .
doi: 10.1038/s41582-019-0302-1
pubmed: 31959938
Martuscello RT, Kerridge CA, Chatterjee D, et al. Gene expression analysis of the cerebellar cortex in essential tremor. Neurosci Lett. 2020;721:134540. https://doi.org/10.1016/j.neulet.2019.134540 .
doi: 10.1016/j.neulet.2019.134540
pubmed: 31707044
Martuscello RT, Louis ED, Faust PL. A stainless protocol for high quality RNA isolation from laser capture microdissected Purkinje cells in the human post-mortem cerebellum. J Vis Exp. 2019;143. https://doi.org/10.3791/58953 .
Gionco JT, Hartstone WG, Martuscello RT, et al. Essential tremor versus “ET-plus”: a detailed postmortem study of cerebellar pathology. Cerebellum. 2021;20(6):904–12. https://doi.org/10.1007/s12311-021-01263-6 .
doi: 10.1007/s12311-021-01263-6
pubmed: 33768479
pmcid: 8972074
Dowd H, Zdrodowska MA, Radler KH, et al. Prospective longitudinal study of gait and balance in a cohort of elderly essential tremor patients. Front Neurol. 2020;11:1–14. https://doi.org/10.3389/fneur.2020.581703 .
doi: 10.3389/fneur.2020.581703
Consensus recommendations for the postmortem diagnosis of Alzheimer’s disease. The National Institute on Aging, and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer’s Disease. Neurobiol Aging. 1997;18:S1–2. https://doi.org/10.1016/S0197-4580(97)00057-2 .
Barton AJL, Pearson RCA, Najlerahim A, Harrison PJ. Pre- and postmortem influences on brain RNA. J Neurochem. 1993;61(1):1–11. https://doi.org/10.1111/j.1471-4159.1993.tb03532.x .
doi: 10.1111/j.1471-4159.1993.tb03532.x
pubmed: 7685811
Popova T, Mennerich D, Weith A, Quast K. Effect of RNA quality on transcript intensity levels in microarray analysis of human post-mortem brain tissues. BMC Genomics. 2008;9(91). https://doi.org/10.1186/1471-2164-9-91 .
Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 2006;112(4):389–404. https://doi.org/10.1007/s00401-006-0127-z .
doi: 10.1007/s00401-006-0127-z
pubmed: 16906426
pmcid: 3906709
Braak H, Braak E. Diagnostic criteria for neuropathologic assessment of Alzheimer’s disease. Neurobiol Aging. 1997;18:S85–8. https://doi.org/10.1016/s0197-4580(97)00062-6 .
doi: 10.1016/s0197-4580(97)00062-6
pubmed: 9330992
Mirra S. The CERAD neuropathology protocol and consensus recommendations for the postmortem diagnosis of Alzheimer's disease: a commentary. Neurobiol Aging. 1997;18:S91–4. https://doi.org/10.1016/s0197-4580(97)00058-4 .
doi: 10.1016/s0197-4580(97)00058-4
pubmed: 9330994
Kim D, Langmead B, Salzberg SL. HISAT: a fast spliced aligner with low memory requirements. Nat Methods. 2015;12(4):357–60. https://doi.org/10.1038/nmeth.3317 .
doi: 10.1038/nmeth.3317
pubmed: 25751142
pmcid: 4655817
Anders S, Pyl PT, Huber W. HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics. 2015;31(2):166–9. https://doi.org/10.1093/bioinformatics/btu638 .
doi: 10.1093/bioinformatics/btu638
pubmed: 25260700
Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. https://doi.org/10.1186/s13059-014-0550-8 .
doi: 10.1186/s13059-014-0550-8
pubmed: 25516281
pmcid: 4302049
Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545–50. https://doi.org/10.1073/pnas.0506580102 .
doi: 10.1073/pnas.0506580102
pubmed: 16199517
pmcid: 1239896
Mootha VK, Lindgren CM, Eriksson K-F, et al. PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34(3):267–73. https://doi.org/10.1038/ng1180 .
doi: 10.1038/ng1180
pubmed: 12808457
Szklarczyk D, Morris JH, Cook H, et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 2017;45(D1):D362–D8. https://doi.org/10.1093/nar/gkw937 .
doi: 10.1093/nar/gkw937
pubmed: 27924014
Tio M, Tan EK. Genetics of essential tremor. Parkinsonism Relat Disord. 2016;22(Suppl 1):S176–8. https://doi.org/10.1016/j.parkreldis.2015.09.022 .
doi: 10.1016/j.parkreldis.2015.09.022
pubmed: 26411503
Louis ED. ‘Essential tremor’ or ‘the essential tremors’: is this one disease or a family of diseases? Neuroepidemiology. 2014;42(2):81–9. https://doi.org/10.1159/000356351 .
doi: 10.1159/000356351
pubmed: 24335621
Jimenez-Jimenez FJ, Alonso-Navarro H, Garcia-Martin E, et al. Genomic markers for essential tremor. Pharmaceuticals (Basel). 2021;14(6). https://doi.org/10.3390/ph14060516 .
Louis ED, Bares M, Benito-Leon J, et al. Essential tremor-plus: a controversial new concept. Lancet Neurol. 2019;19(3):266–70. https://doi.org/10.1016/S1474-4422(19)30398-9 .
doi: 10.1016/S1474-4422(19)30398-9
pubmed: 31767343
Bhatia KP, Bain P, Bajaj N, et al. Consensus statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society. Mov Disord. 2018;33(1):75–87. https://doi.org/10.1002/mds.27121 .
doi: 10.1002/mds.27121
pubmed: 29193359
Stefansson H, Steinberg S, Petursson H, et al. Variant in the sequence of the LINGO1 gene confers risk of essential tremor. Nat Genet. 2009;41:277–9. https://doi.org/10.1038/ng.299 .
doi: 10.1038/ng.299
pubmed: 19182806
pmcid: 3740956
Clark LN, Park N, Kisselev S, et al. Replication of the LINGO1 gene association with essential tremor in a North American population. Eur J Hum Genet. 2010;18:838–43. https://doi.org/10.1038/ejhg.2010.27 .
doi: 10.1038/ejhg.2010.27
pubmed: 20372186
pmcid: 2987362
Thier S, Lorenz D, Nothnagel M, et al. Polymorphisms in the glial glutamate transporter SLC1A2 are associated with essential tremor. Neurology. 2012;79(3). https://doi.org/10.1212/WNL.0b013e31825fdeed .
Lee M, Cheng MM, Lin C-Y, et al. Decreased EAAT2 protein expression in the essential tremor cerebellar cortex. Acta Neuropathol Commun. 2014;2(157):1–11. https://doi.org/10.1186/s40478-014-0157-z .
doi: 10.1186/s40478-014-0157-z
Xiao B, Deng X, Ng EY, et al. GWAS-linked PPARGC1A variant in Asian patients with essential tremor. Brain. 2017;140(4):e24. https://doi.org/10.1093/brain/awx027 .
doi: 10.1093/brain/awx027
pubmed: 28334983
Merner ND, Girard SL, Catoire H, et al. Exome sequencing identifies FUS mutations as a cause of essential tremor. Am J Hum Genet. 2012;91:313–9. https://doi.org/10.1016/j.ajhg.2012.07.002 .
doi: 10.1016/j.ajhg.2012.07.002
pubmed: 22863194
pmcid: 3415547
Parmalee N, Mirzozoda K, Kisselev S, et al. Genetic analysis of the FUS/TLS gene in essential tremor. Eur J Neurol. 2013;20(3):534–9. https://doi.org/10.1111/ene.12023 .
doi: 10.1111/ene.12023
pubmed: 23114103
Hor H, Francescatto L, Bartesaghi L, et al. Missense mutations in TENM4, a regulator of axon guidance and central myelination, cause essential tremor. Hum Mol Genet. 2015;24(20):5677–86. https://doi.org/10.1093/hmg/ddv281 .
doi: 10.1093/hmg/ddv281
pubmed: 26188006
pmcid: 4692992
Sánchez E, Bergareche A, Krebs CE, et al. SORT1 mutation resulting in sortilin deficiency and p75NTR upregulation in a family with essential tremor. ASN Neuro. 2015;7(4):1–13. https://doi.org/10.1177/1759091415598290 .
doi: 10.1177/1759091415598290
Gulsuner HU, Gulsuner S, Mercan FN, et al. Mitochondrial serine protease HTRA2 p.G399S in a kindred with essential tremor and Parkinson disease. PNAS. 2014;111(51):18285–90. https://doi.org/10.1073/pnas.1419581111 .
doi: 10.1073/pnas.1419581111
pubmed: 25422467
pmcid: 4280582
Sun Q-Y, Xu Q, Tian Y, et al. Expansion of GGC repeat in the human-specific NOTCH2NLC gene is associated with essential tremor. Brain. 2020;143(1):222–33. https://doi.org/10.1093/brain/awz372 .
doi: 10.1093/brain/awz372
pubmed: 31819945
Leng X-R, Qi X-H, Zhou Y-T, Wang Y-P. Gain-of-function mutation p.Arg225Cys in SCN11A causes familial episodic pain and contributes to essential tremor. J Hum Genet. 2017;62:641–6. https://doi.org/10.1038/jhg.2017.21 .
doi: 10.1038/jhg.2017.21
pubmed: 28298626
Liao C, Sarayloo F, Rochefort D, et al. Multiomics analyses identify genes and pathways relevant to essential tremor. Mov Disord. 2020;35(7):1153–62. https://doi.org/10.1002/mds.28031 .
doi: 10.1002/mds.28031
pubmed: 32249994
Neueder A. RNA-mediated disease mechanisms in neurodegenerative disorders. J Mol Biol. 2019;431(9):1780–91. https://doi.org/10.1016/j.jmb.2018.12.012 .
doi: 10.1016/j.jmb.2018.12.012
pubmed: 30597161
Montes M, Sanford BL, Comiskey DF, Chandler DS. RNA splicing and disease: animal models to therapies. Trends Genet. 2019;35(1):68–87. https://doi.org/10.1016/j.tig.2018.10.002 .
doi: 10.1016/j.tig.2018.10.002
pubmed: 30466729
Hopfner F, Stevanin G, Müller SH, et al. The impact of rare variants in FUS in essential tremor. Mov Disord. 2015;30(5):721–4. https://doi.org/10.1002/mds.26145 .
doi: 10.1002/mds.26145
pubmed: 25631824
Ortega-Cubero S, Lorenzo-Betancor O, Lorenzo E, et al. Fused in sarcoma (FUS) gene mutations are not a frequent cause of essential tremor in Europeans. Neurobiol Aging. 2013;34:2441.e9–e11. https://doi.org/10.1016/j.neurobiolaging.2013.04.024 .
doi: 10.1016/j.neurobiolaging.2013.04.024
pubmed: 23731953
Kino Y, Washizu C, Kurosawa M, et al. FUS/TLS deficiency causes behavioral and pathological abnormalities distinct from amyotrophic lateral sclerosis. Acta Neuropathol Commun. 2015;3(24). https://doi.org/10.1186/s40478-015-0202-6 .
Uhlén M, Fagerberg L, Hallström BM, et al. Proteomics. Tissue-based map of the human proteome. Science. 2015;347(6220). https://doi.org/10.1126/science.1260419 .
Santulli G, Marks A. Essential roles of intracellular calcium release channels in muscle, brain, metabolism, and aging. Curr Mol Pharmacol. 2015;8:1–17. https://doi.org/10.2174/1874467208666150507105105 .
doi: 10.2174/1874467208666150507105105
Khodakhah K, Armstrong CM. Inositol trisphosphate and ryanodine receptors share a common functional Ca2+ pool in cerebellar Purkinje neurons. Biophys J. 1997;73:3349–57. https://doi.org/10.1016/S0006-3495(97)78359-0 .
doi: 10.1016/S0006-3495(97)78359-0
pubmed: 9414245
pmcid: 1181236
Gomez LC, Kawaguchi S-Y, Collin T, et al. Influence of spatially segregated IP 3-producing pathways on spike generation and transmitter release in Purkinje cell axons. Proc Natl Acad Sci U S A. 2020;117(20):11097–108. https://doi.org/10.1073/pnas.2000148117 .
doi: 10.1073/pnas.2000148117
pubmed: 32358199
pmcid: 7245073
Martinez Leo E, Secura Campos M. Systemic oxidative stress: a key point in neurodegeneration - a review. J Nutr Health Aging. 2019;23(8):694–9. https://doi.org/10.1007/s12603-019-1240-8 .
doi: 10.1007/s12603-019-1240-8
pubmed: 31560025
Singh A, Kukreti R, Saso L, Kukreti S. Oxidative stress: a Key modulator in neurodegenerative diseases. Molecules. 2019;24:1–20. https://doi.org/10.3390/molecules24081583 .
doi: 10.3390/molecules24081583
Dogu O, Louis ED, Tamer LT, et al. Elevated blood lead concentrations in essential tremor: a case–control study in Mersin, Turkey. Environ Health Perspect. 2007;115(11):1564–8. https://doi.org/10.1289/ehp.10352 .
doi: 10.1289/ehp.10352
pubmed: 18007985
pmcid: 2072853
Louis ED, Jurewicz EC, Applegate L, et al. Association between essential tremor and blood lead concentration. Environ Health Perspect. 2003;111(14):1707–11. https://doi.org/10.1289/ehp.6404 .
doi: 10.1289/ehp.6404
pubmed: 14594619
pmcid: 1241711
Louis ED, Factor-Litvak P, Gerbin M, et al. Blood harmane, blood lead, and severity of hand tremor: evidence of additive effects. Neurotoxicology. 2011;32:227–32. https://doi.org/10.1016/j.neuro.2010.12.002 .
doi: 10.1016/j.neuro.2010.12.002
pubmed: 21145352
Almeida Lopes ACB, Peixe TS, Mesas AE, Paoliello MMB. Lead exposure and oxidative stress: a systematic review. Rev Environ Contam Toxicol. 2016;236:193-238. Springer.
Sammi SR, Agim ZS, Cannon JR. Harmane-induced selective dopaminergic neurotoxicity in Caenorhabditis elegans. Toxicol Sci. 2018;161(2):335–48. https://doi.org/10.1093/toxsci/kfx223 .
doi: 10.1093/toxsci/kfx223
pubmed: 29069497
Wilkins HM, Kirchhof D, Manning E, Joseph JW, Linseman DA. Mitochondrial glutathione transport is a key determinant of neuronal susceptibility to oxidative and nitrosative stress. J Biol Chem. 2013;288(7):5091–101. https://doi.org/10.1074/jbc.M112.405738 .
doi: 10.1074/jbc.M112.405738
pubmed: 23283974
pmcid: 3576114
Gu F, Chauhan V, Chauhan A. Glutathione redox imbalance in brain disorders. Curr Opin Clin Nutr Metab Care. 2015;19(1):89–95. https://doi.org/10.1097/MCO.0000000000000134 .
doi: 10.1097/MCO.0000000000000134
Chen WW, Zhang X, Huang WJ. Role of neuroinflammation in neurodegenerative diseases (Review). Mol Med Rep. 2016;13(4):3391–6. https://doi.org/10.3892/mmr.2016.4948 .
doi: 10.3892/mmr.2016.4948
pubmed: 26935478
pmcid: 4805095
Louis ED, Faust PL. Essential tremor: the most common form of cerebellar degeneration? Cereb Ataxias. 2020;7(12):1–10. https://doi.org/10.1186/s40673-020-00121-1 .
doi: 10.1186/s40673-020-00121-1
Muruzheva ZM, Ivleva IS, Traktirov DS, Zubov AS, Karpenko MN. The relationship between serum interleukin-1beta, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha levels and clinical features in essential tremor. Int J Neurosci. 2021;1-10. https://doi.org/10.1080/00207454.2020.1865952 .
Louis ED. The essential tremors: evolving concepts of a family of diseases. Front Neurol. 2021;12. https://doi.org/10.3389/fneur.2021.650601 .