The association between mutations in the lysosomal protein glucocerebrosidase and parkinsonism
| Autor: | DePaolo, J., Goker-Alpan, O., Samaddar, T., Lopez, G., Sidransky, E. |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Adult
Lewy Body Disease Male Gaucher Disease DNA Mutational Analysis Genetic Counseling Middle Aged Hippocampus Article nervous system diseases Substantia Nigra Parkinsonian Disorders Risk Factors Mutation Ethnicity alpha-Synuclein Glucosylceramidase Humans Enzyme Replacement Therapy Female Genetic Predisposition to Disease Child Lysosomes Aged |
| Popis: | A body of work has emerged over the past decade demonstrating a relationship between mutations in glucocerebrosidase (GBA), the gene implicated in Gaucher disease, and the development of parkinsonism. Several different lines of research support this relationship. First, patients with Gaucher disease who are homozygous for mutations in GBA have a higher than expected propensity to develop Parkinson disease (PD). Furthermore, carriers of GBA mutations, particularly family members of patients with Gaucher disease have displayed an increased rate of parkinsonism. Subsequently, investigators from centers around the world screened cohorts of patients with parkinsonism for GBA mutations and found that overall, subjects with Parkinson disease as well as other Lewy body disorders have at least a five–fold increase in the number of carriers of GBA mutations as compared to age matched controls. In addition, neuropathologic studies of subjects with parkinsonism carrying GBA mutations demonstrate Lewy bodies, depletion of neurons of the substantia nigra and involvement of hippocampal layers CA2−4. While the basis for this association has yet to be elucidated, evidence continues to support the role of GBA as a Parkinson risk factor across different centers, synucleinopathies and ethnicities. Further studies of the association between Gaucher disease and parkinsonism will stimulate new insights into the pathophysisology of the two disorders, and will prove crucial for both genetic counseling of patients and family members and the design of relevant therapeutic strategies for specific patients with parkinsonism. |
| Databáze: | OpenAIRE |
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