The Molecular Impact of Glucosylceramidase Beta 1 (Gba1) in Parkinson's Disease: a New Genetic State of the Art.

التفاصيل البيبلوغرافية
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 Feb 13. Date of Electronic Publication: 2024 Feb 13.
Publication Model:	Ahead of Print
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-
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.)
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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
تواريخ الأحداث:	Date Created: 20240212 Latest Revision: 20240212
رمز التحديث:	20240213
DOI:	10.1007/s12035-024-04008-8
PMID:	38347286
قاعدة البيانات:	MEDLINE

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تدمد:	1559-1182
DOI:	10.1007/s12035-024-04008-8