دورية أكاديمية
The Molecular Impact of Glucosylceramidase Beta 1 (Gba1) in Parkinson's Disease: a New Genetic State of the Art.
العنوان: | The Molecular Impact of Glucosylceramidase Beta 1 (Gba1) in Parkinson's Disease: a New Genetic State of the Art. |
---|---|
المؤلفون: | Dos Santos JCC; Christus University Center, UNICHRISTUS, Fortaleza, Ceara, Brazil. julio.santos@alu.ufc.br.; Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil. julio.santos@alu.ufc.br.; Postgraduate Program in Morphofunctional Sciences, Federal University of Ceará, Fortaleza, Ceara, Brazil. julio.santos@alu.ufc.br., Mano GBC; Faculty of Medical Sciences of, Santa Casa de São Paulo, São Paulo, SP, Brazil., da Cunha Barreto-Vianna AR; Federal University of Paraná, Pelotas, Parana, Brazil., Garcia TFM; Multicampi School of Medical Sciences, Federal University of Rio Grande Do Norte, Caico, Rio Grande Do Norte, Brazil., de Vasconcelos AV; Christus University Center, UNICHRISTUS, Fortaleza, Ceara, Brazil., Sá CSG; Christus University Center, UNICHRISTUS, Fortaleza, Ceara, Brazil., de Souza Santana SL; Barão de Mauá University Center, CBM, Ribeirão Preto, São Paulo, Brazil., Farias AGP; Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil., Seimaru B; Barão de Mauá University Center, CBM, Ribeirão Preto, São Paulo, Brazil., Lima MPP; Christus University Center, UNICHRISTUS, Fortaleza, Ceara, Brazil., Goes JVC; Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil.; Post-Graduate Program of Pathology, Federal University of Ceara, Fortaleza, Ceara, Brazil., Gusmão CTP; Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil., Junior HLR; Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil.; Post-Graduate Program of Pathology, Federal University of Ceara, Fortaleza, Ceara, Brazil.; Post-Graduate Program in Medical Science, Federal University of Ceara, Fortaleza, Ceara, Brazil. |
المصدر: | Molecular neurobiology [Mol Neurobiol] 2024 Sep; Vol. 61 (9), pp. 6754-6770. Date of Electronic Publication: 2024 Feb 13. |
نوع المنشور: | Journal Article; Review |
اللغة: | English |
بيانات الدورية: | Publisher: Humana Press Country of Publication: United States NLM ID: 8900963 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-1182 (Electronic) Linking ISSN: 08937648 NLM ISO Abbreviation: Mol Neurobiol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Clifton, NJ : Humana Press, c1987- |
مواضيع طبية MeSH: | Glucosylceramidase*/genetics , Parkinson Disease*/genetics , Parkinson Disease*/enzymology , Mutation*/genetics, Humans ; Animals ; Genetic Predisposition to Disease ; alpha-Synuclein/genetics ; alpha-Synuclein/metabolism |
مستخلص: | Parkinson's disease (PD) is a neurodegenerative disorder affecting 2-3% of those aged over 65, characterized by motor symptoms like slow movement, tremors, and muscle rigidity, along with non-motor symptoms such as anxiety and dementia. Lewy bodies, clumps of misfolded proteins, contribute to neuron loss in PD. Mutations in the GBA1 gene are considered the primary genetic risk factor of PD. GBA1 mutations result in decreased activity of the lysosomal enzyme glucocerebrosidase (GCase) resulting in α-synuclein accumulation. We know that α-synuclein aggregation, lysosomal dysfunction, and endoplasmic reticulum disturbance are recognized factors to PD susceptibility; however, the molecular mechanisms connecting GBA1 gene mutations to increased PD risk remain partly unknown. Thus, in this narrative review conducted according to a systematic review method, we aimed to present the main contributions arising from the molecular impact of the GBA1 gene to the pathogenesis of PD providing new insights into potential impacts for advances in the clinical care of people with PD, a neurological disorder that has contributed to the substantial increase in the global burden of disease accentuated by the aging population. In summary, this narrative review highlights the multifaceted impact of GBA1 mutations in PD, exploring their role in clinical manifestations, genetic predispositions, and molecular mechanisms. The review emphasizes the importance of GBA1 mutations in both motor and non-motor symptoms of PD, suggesting broader therapeutic and management strategies. It also discusses the potential of CRISPR/Cas9 technology in advancing PD treatment and the need for future research to integrate these diverse aspects for improved diagnostics and therapies. (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) |
References: | Pradas E, Martinez-Vicente M (2023) The consequences of GBA deficiency in the autophagy-lysosome system in PD associated with GBA. Cells 12(1):191. https://doi.org/10.3390/cells12010191. (PMID: 366119849818455) Zhang Y, Chen J, Xu C, Feng J, Li J (2020) Effects of glucocerebrosidase gene polymorphisms and mutations on the risk of PD dementia: a ambroxol meta-analysis. Neurosci Lett 1(714):134544. https://doi.org/10.1016/j.neulet.2019.134544. Fais M, Dore A, Galioto M, Galleri G, Crosio C, Iaccarino C (2021) PD-related genes and lipid alteration. Int J Mol Sci 22(14):7630. https://doi.org/10.3390/ijms22147630. (PMID: 342992488305702) Gegg ME, Menozzi E, Schapira AHV (2022) Glucocerebrosidase-associated Parkinson disease: pathogenic mechanisms and potential drug treatments. Neurobiol Dis 166:105663. https://doi.org/10.1016/j.nbd.2022.105663. (PMID: 35183702) Pang SYY, Lo RCN, Ho PWL, Liu HF, Chang EES, Leung CT et al (2022) LRRK2, GBA and their interaction in the regulation of autophagy: implications on therapeutics in PD. Transl Neurodegener 11(5):1–14. https://doi.org/10.1186/s40035-022-00281-6. Aasly JO (2020) Long-term outcomes of genetic PD. J Mov Disord 13(2):81–96. https://doi.org/10.14802/jmd.19080. (PMID: 324984947280945) Senkevich K, Rudakou U, Gan-Or Z (2022) New therapeutic approaches to Parkinson's disease targeting GBA, LRRK2 and Parkin. Neuropharmacology 202:108822. https://doi.org/10.1016/j.neuropharm.2021.108822. Kuo MC, Liu SC, Hsu YF, Wu RM (2021) The role of noncoding RNAs in PD: biomarkers and associations with pathogenic pathways. J Biomed Sci 28(1):78. https://doi.org/10.1186/s12929-021-00775-x. (PMID: 347944328603508) Kern F, Fehlmann T, Violich I, Alsop E, Hutchins E, Kahraman M et al (2021) Deep sequencing of sncRNAs reveals hallmarks and regulatory modules of the transcriptome during PD progression. Nat Aging 1(3):309–322. https://doi.org/10.1038/s43587-021-00042-6. (PMID: 37118411) Chahine LM, Qiang J, Ashbridge E, Minger J, Yearout D, Horn S et al (2013) Clinical and biochemical differences in patients having Parkinson disease with vs without GBA mutations. JAMA Neurol 70(7):852–858. https://doi.org/10.1001/jamaneurol.2013.1274. (PMID: 236997523762458) Smith L, Schapira AHV (2022) GBA variants and Parkinson disease: mechanisms and treatments. Cells 11(8):1261. https://doi.org/10.3390/cells11081261. (PMID: 354559419029385) Arias-Fuenzalida J, Jarazo J, Qing X, Walter J, Gomez-Giro G, Nickels SL et al (2017) FACS-assisted CRISPR-Cas9 genome editing facilitates PD modeling. Stem Cell Reports 9(5):1423–1431. https://doi.org/10.1016/j.stemcr.2017.08.026. (PMID: 289889855830965) Luo J, Padhi P, Jin H, Anantharam V, Zenitsky G, Wang Q, Willette AA et al (2019) Utilization of the CRISPR-Cas9 gene editing system to dissect neuroinflammatory and neuropharmacological mechanisms in PD. J Neuroimmune Pharmacol 14(4):595–607. https://doi.org/10.1007/s11481-019-09844-3. (PMID: 308792406746615) Pinjala P, Tryphena KP, Prasad R, Khatri DK, Sun W, Singh SB et al (2023) CRISPR/Cas9 assisted stem cell therapy in PD. Biomater Res 27(1):46. https://doi.org/10.1186/s40824-023-00381-y. (PMID: 3719400510190035) Li Q, Jing Y, Lun P, Liu X, Sun P (2021) Association of gender and age at onset with glucocerebrosidase associated PD: a systematic review and meta-analysis. Neurol Sci 42(6):2261–2271. https://doi.org/10.1007/s10072-021-05230-1. (PMID: 33837876) Filippi M, Balestrino R, Basaia S, Agosta F (2022) Neuroimaging in glucocerebrosidase-associated parkinsonism: a systematic review. Mov Disord 37(7):1375–1393. https://doi.org/10.1002/mds.29047. (PMID: 355218999546404) Yang SY, Gegg M, Chau D, Schapira A (2020) Glucocerebrosidase activity, cathepsin D and monomeric α-synuclein interactions in a stem cell derived neuronal model of a PD associated GBA1 mutation. Neurobiol Dis 134:104620. https://doi.org/10.1016/j.nbd.2019.104620. (PMID: 316345586983928) Galvagnion C, Marlet FR, Cerri S, Schapira AHV, Blandini F, Di Monte DA (2022) Sphingolipid changes in Parkinson L444P GBA mutation fibroblasts promote α-synuclein aggregation. Brain 145(3):1038–1051. https://doi.org/10.1093/brain/awab371. (PMID: 353620229050548) Vieira SRL, Schapira AHV (2022) Glucocerebrosidase mutations and Parkinson disease. J Neural Transm (Vienna) 129(9):1105–1117. https://doi.org/10.1007/s00702-022-02531-3. (PMID: 35932311) Toffoli M, Higgins A, Lee C, Koletsi S, Chen X, Eberle M et al (2021) Intronic haplotypes in the GBA gene do not predict age at diagnosis of PD. Mov Disord 36(6):1456–1460. https://doi.org/10.1002/mds.28616. (PMID: 340088878436748) Ortega RA, Bressman SB, Raymond D, Ozelius LJ, Katsnelson V, Leaver K et al (2022) Differences in sex-specific frequency of glucocerebrosidase variant carriers and familial parkinsonism. Mov Disord 37(11):2217–2225. https://doi.org/10.1002/mds.29197. (PMID: 360543069669136) Wallom KL, Fernández-Suárez ME, Priestman DA, Te Vruchte D, Huebecker M, Hallett PJ et al (2022) Glycosphingolipid metabolism and its role in ageing and PD. Glycoconj J 39(1):39–53. https://doi.org/10.1007/s10719-021-10023-x. (PMID: 34757540) Vieira SRL, Schapira AHV (2021) Glucocerebrosidase mutations: a paradigm for neurodegeneration pathways. Free Radic Biol Med 1(175):42–55. https://doi.org/10.1016/j.freeradbiomed.2021.08.230. Riboldi GM, Vialle RA, Navarro E, Udine E, Lopes KP, Humphrey J et al (2022) Transcriptome deregulation of peripheral monocytes and whole blood in GBA-related PD. Mol Neurodegeneration 17(52):1–17. https://doi.org/10.1186/s13024-022-00554-8. Milenkovic I, Blumenreich S, Futerman AH (2022) GBA mutations, glucosylceramide and PD. Curr Opin Neurobiol 72:148–154. https://doi.org/10.1016/j.conb.2021.11.004. (PMID: 34883387) Isonaka R, Goldstein DS, Zhu W, Yoon E, Ehrlich D, Schindler AB et al (2021) α-Synuclein deposition in sympathetic nerve fibers in genetic forms of PD. Mov Disord 36(10):2346–2357. https://doi.org/10.1002/mds.28667. (PMID: 340762989014961) Matsumoto SI, Sato S, Otake K, Kosugi Y (2022) Highly-sensitive simultaneous quantitation of glucosylsphingosine and galactosylsphingosine in human cerebrospinal fluid by liquid chromatography/tandem mass spectrometry. J Pharm Biomed Anal 217:114852. https://doi.org/10.1016/j.jpba.2022.114852. (PMID: 35636011) Gegg ME, Verona G, Schapira AHV (2020) Glucocerebrosidase deficiency promotes release of α-synuclein fibrils from cultured neurons. Hum Mol Genet 29(10):1716–1728. https://doi.org/10.1093/hmg/ddaa085. (PMID: 323918867322566) Sanyal A, DeAndrade MP, Novis HS, Lin S, Chang J, Lengacher N et al (2020) Lysosome and inflammatory defects in GBA1-mutant astrocytes are normalized by lrrk2 inhibition. Mov Disord 35(5):760–773. https://doi.org/10.1002/mds.27994. (PMID: 320347998167931) Thaler A, Omer N, Giladi N, Gurevich T, Bar-Shira A, Gana-Weisz M et al (2021) Mutations in GBA and LRRK2 are not associated with increased inflammatory markers. J Parkinsons Dis 11(3):1285–1296. https://doi.org/10.3233/JPD-212624. (PMID: 339985498461659) Biswas A, Sadhukhan D, Biswas A, Das SK, Banerjee TK, Bal PS et al (2021) Identification of GBA mutations among neurodegenerative disease patients from eastern India. Neurosci Lett 23(751):135816. https://doi.org/10.1016/j.neulet.2021.135816. Amami P, De Santis T, Invernizzi F, Garavaglia B, Albanese A (2021) Impulse control behavior in GBA-mutated parkinsonian patients. J Neurol Sci 15(421):117291. https://doi.org/10.1016/j.jns.2020.117291. Pachi I, Koros C, Simitsi AM, Papadimitriou D, Bougea A, Prentakis A et al (2021) Apathy: an underestimated feature in GBA and LRRK2 non-manifesting mutation carriers. Parkinsonism Relat Disord 91:1–8. https://doi.org/10.1016/j.parkreldis.2021.08.008. (PMID: 34425330) Maple-Grødem J, Paul KC, Dalen I, Ngo KJ, Wong D, Macleod AD et al (2021) Lack of association between GBA mutations and motor complications in European and American PD cohorts. J Parkinsons Dis 11(4):1569–1578. https://doi.org/10.3233/JPD-212657. (PMID: 342759088609705) Ghatti S, Yoon E, Lopez G, Ehrlich D, Horovitz SG (2022) Imaging and genetics in PD: assessment of the GBA1 mutation. J Neurol 269(10):5347–5355. https://doi.org/10.1007/s00415-022-11181-0. (PMID: 3560446710402751) Leocadi M, Canu E, Donzuso G, Stojkovic T, Basaia S, Kresojević N et al (2022) Longitudinal clinical, cognitive, and neuroanatomical changes over 5 years in GBA-positive PD patients. J Neurol 269(3):1485–1500. https://doi.org/10.1007/s00415-021-10713-4. (PMID: 34297177) Huh YE, Chiang MSR, Locascio JJ, Liao Z, Liu G, Choudhury K et al (2020) β-Glucocerebrosidase activity in GBA-linked Parkinson disease: the type of mutation matters. Neurology 95(6):e685–e696. https://doi.org/10.1212/WNL.0000000000009989. (PMID: 325409377455354) Stoker TB, Camacho M, Winder-Rhodes S, Liu G, Scherzer CR, Foltynie T et al (2020) Impact of GBA1 variants on long-term clinical progression and mortality in incident PD. J Neurol Neurosurg Psychiatry 91(7):695–702. https://doi.org/10.1136/jnnp-2020-322857. (PMID: 32303560) Höglinger G, Schulte C, Jost WH, Storch A, Woitalla D, Krüger R et al (2022) GBA-associated PD: chances and obstacles for targeted treatment strategies. J Neural Transm 129:1219–1233. https://doi.org/10.1007/s00702-022-02511-7. (PMID: 35639160) Macías-García D, Periñán MT, Muñoz-Delgado L, Jesús S, Jimenez-Jaraba MV, Buiza-Rueda D et al (2022) Increased stroke risk in patients with PD with LRRK2 mutations. Mov Disord 37(5):225–227. https://doi.org/10.1002/mds.28863. (PMID: 34859503) Li B, Zhao G, Zhou Q, Xie Y, Wang Z, Fang Z et al (2021) Gene4PD: a comprehensive genetic database of PD. Front Neurosci 26(15):679568. https://doi.org/10.3389/fnins.2021.679568. Shi C, Zheng Z, Wang Q, Wang C, Zhang D, Zhang M et al (2016) Exploring the effects of genetic variants on clinical profiles of PD assessed by the unified PD rating scale and the Hoehn-Yahr stage. PLoS ONE 11(6):e0155758. https://doi.org/10.1371/journal.pone.0155758. (PMID: 272995234907455) Blauwendraat C, Reed X, Krohn L, Heilbron K, Bandres-Ciga S, Tan M et al (2020) Genetic modifiers of risk and age at onset in GBA associated PD and Lewy body dementia. Brain 143(1):234–248. https://doi.org/10.1093/brain/awz350. (PMID: 31755958) Chen Y, Sam R, Sharma P, Chen L, Do J, Sidransky E (2020) Glucocerebrosidase as a therapeutic target for PD. Expert Opin Ther Targets 24(4):287–294. https://doi.org/10.1080/14728222.2020.1733970. (PMID: 321067257113099) Buniello A, MacArthur JAL, Cerezo M, Harris LW, Hayhurst J, Malangone C et al (2019) The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Res 47(D1):D1005–D1012. (PMID: 30445434) Rebbeck TR, Mahal B, Maxwell KN, Garraway IP, Yamoah K (2022) The distinct impacts of race and genetic ancestry on health. Nat Med 28(5):890–893. https://doi.org/10.1038/s41591-022-01796-1. (PMID: 35534567) Greuel A, Trezzi JP, Glaab E, Ruppert MC, Maier F, Jäger C et al (2020) GBA variants in PD: clinical, metabolomic, and multimodal neuroimaging phenotypes. Mov Disord 35(12):2201–2210. https://doi.org/10.1002/mds.28225. (PMID: 32853481) Menozzi E, Schapira AHV (2021) Exploring the genotype–phenotype correlation in GBA-Parkinson disease: clinical aspects, biomarkers, and potential modifiers. Front Neurol 12:694764. https://doi.org/10.3389/fneur.2021.694764. (PMID: 342488308264189) Ye H, Robak LA, Yu M, Cykowski M, Shulman JM (2023) Genetics and pathogenesis of Parkinson’s syndrome. Annu Rev Patho 24(18):95–121. https://doi.org/10.1146/annurev-pathmechdis-031521-034145. Kaiser S, Zhang L, Mollenhauer B, Jacob J, Longerich S, Del-Aguila J et al (2023) A proteogenomic view of PD causality and heterogeneity. NPJ Parkinsons Dis 9(1):1–18. https://doi.org/10.1038/s41531-023-00461-9. Zhang H, Yao L, Zheng Z, Koc S, Lu G (2022) The role of non-coding RNAs in the pathogenesis of PD: recent advancement. Pharmaceuticals 5(7):811. https://doi.org/10.3390/ph15070811. Zhang P, Rasheed M, Liang J, Wang C, Feng L, Chen Z (2022) Emerging potential of exosomal non-coding RNA in PD: a review. Front Aging Neurosci 2022:14. https://doi.org/10.3389/fnagi.2022.819836. Miyoshi K, Hagita H, Horiguchi T, Tanimura A, Noma T (2022) Redefining GBA gene structure unveils the ability of Cap-independent, IRES-dependent gene regulation. Commun Biolog 5(1):639. https://doi.org/10.1038/s42003-022-03577-5. Goh SY, Chao YX, Dheen ST, Tan EK, Tay SS (2019) Role of microRNAs in PD. Int J Mol Sci 20(22):5649. https://doi.org/10.3390/ijms20225649. (PMID: 317180956888719) Takeuchi S, Yamamoto M, Matsumoto S, Kenjo E, Karashima M, Ikeda Y (2022) Pinpoint modification strategy for stabilization of single guide RNA. J Chromatogr B Anal Technol Biomed Life Sci 1192:123149. https://doi.org/10.1016/j.jchromb.2022.123149. Safari F, Hatam G, Behbahani AB, Rezai V, Barekati-Mowahed M, Petramfar P et al (2020) CRISPR system: a high-throughput toolbox for research and treatment of PD. Cell Mol Neurobiol 40(4):477–493. https://doi.org/10.1007/s10571-019-00761-w. (PMID: 31773362) Jiang Z, Huang Y, Zhang P, Han C, Lu Y, Mo Z et al (2020) Characterization of a pathogenic variant in GBA for PD with mild cognitive impairment patients. Mol Brain 13(1):102. https://doi.org/10.1186/s13041-020-00637-x. (PMID: 326411467346430) Jo J, Yang L, Tran HD, Yu W, Sun AX, Chang YY et al (2021) Lewy body-like inclusions in human midbrain organoids carrying glucocerebrosidase and α-synuclein mutations. Ann Neurol 90(3):490–505. https://doi.org/10.1002/ana.26166. (PMID: 342880559543721) Kim S, Wong YC, Gao F, Krainc D (2021) Dysregulation of mitochondria-lysosome contacts by GBA1 dysfunction in dopaminergic neuronal models of PD. Nat Commun 12(1):1807. https://doi.org/10.1038/s41467-021-22113-3. (PMID: 337537437985376) Chemla A, Arena G, Saraiva C, Berenguer-Escuder C, Grossmann D, Grünewald A et al (2023) Generation of two induced pluripotent stem cell lines and the corresponding isogenic controls from PD patients carrying the heterozygous mutations c.1290A > G (p.T351A) or c.2067A > G (p.T610A) in the RHOT1 gene encoding Miro1. Stem Cell Res 69:103085. https://doi.org/10.1016/j.scr.2023.103085. (PMID: 3700318110240566) |
معلومات مُعتمدة: | UNI-0210-00007.01.00/23 Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico; #382025/2023-7 Conselho Nacional de Desenvolvimento Científico e Tecnológico |
فهرسة مساهمة: | Keywords: GBA1; Molecular mechanisms; Mutations; Parkinson’s disease |
المشرفين على المادة: | EC 3.2.1.45 (Glucosylceramidase) 0 (alpha-Synuclein) EC 3.2.1.45 (GBA protein, human) |
تواريخ الأحداث: | Date Created: 20240212 Date Completed: 20240821 Latest Revision: 20240826 |
رمز التحديث: | 20240826 |
DOI: | 10.1007/s12035-024-04008-8 |
PMID: | 38347286 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1559-1182 |
---|---|
DOI: | 10.1007/s12035-024-04008-8 |