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The neuroinflammatory role of glucocerebrosidase in Parkinson's disease.
Bo, Ru-Xue; Li, Yan-Yan; Zhou, Tian-Tian; Chen, Nai-Hong; Yuan, Yu-He.
Afiliación
  • Bo RX; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica& Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address: boruxue@imm.ac.cn.
  • Li YY; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica& Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address: liyanyan@imm.ac.cn.
  • Zhou TT; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica& Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address: tianszhou8@163.com.
  • Chen NH; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica& Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address: chennh@imm.ac.cn.
  • Yuan YH; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica& Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address: yuanyuhe@imm.ac.cn.
Neuropharmacology ; 207: 108964, 2022 04 01.
Article en En | MEDLINE | ID: mdl-35065083
The lysosomal enzyme glucocerebrosidase (GCase), encoded by the GBA1 gene, is a membrane-associated protein catalyzing the cleavage of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph). Homologous GBA1 mutations cause Gaucher disease (GD) and heterologous mutations cause Parkinson's disease (PD). Importantly, heterologous GBA1 mutations are recognized as the second risk factor of PD. The pathological features of PD are Lewy neurites (LNs) and Lewy bodies (LBs) composed of pathological α-synuclein. Oxidative stress, inflammatory response, autophagic impairment, and α-synuclein accumulation play critical roles in PD pathogenic cascades, but the pathogenesis of PD has not yet been fully elucidated. What's more, PD treatment drugs can only relieve symptoms to a certain extent, but cannot alleviate neurodegenerative progression. Therefore, it's urgent to explore new targets that can alleviate the neurodegenerative process. Deficient GCase can cause lysosomal dysfunction, obstructing the metabolism of α-synuclein. Meanwhile, GCase dysfunction causes accumulation of its substrates, leading to lipid metabolism disorders. Subsequently, astrocytes and microglia are activated, releasing amounts of pro-inflammatory mediators and causing extensive neuroinflammation. All these cascades can induce neuron damage and death, eventually promoting PD pathology. This review aims to summarize these points and the potential of GCase as an original target to provide some ideas for elucidating the pathogenesis of PD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Enfermedades Neuroinflamatorias / Glucosilceramidasa Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Neuropharmacology Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Enfermedades Neuroinflamatorias / Glucosilceramidasa Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Neuropharmacology Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido