中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (5): 994-995.doi: 10.4103/1673-5374.297076

• 观点:退行性病与再生 • 上一篇    下一篇

遗传学为帕金森病提供了新的个性化治疗靶标

  

  • 出版日期:2021-05-15 发布日期:2020-12-29

Genetics provides new individualized therapeutic targets for Parkinson’s disease

Eric Joshua Garcia, Ellen Sidransky*   

  1. Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
  • Online:2021-05-15 Published:2020-12-29
  • Contact: Ellen Sidransky, MD, idranse@mail.nih.gov.

Abstract: The identification of genes increasing one’s risk of developing common, complex disorders like Parkinson’s disease (PD) can provide novel therapeutic opportunities. A prime example of this are the consequences of mutations in GBA1, the gene responsible for the lysosomal storage disorder Gaucher disease (GD). GD is a multi-system disorder, primarily affecting tissues of the reticuloendothelial system. A subset of patients with GD also have neuronopathic manifestations (types 2 and 3 GD). In addition, there is an established association between GD and seemingly-unrelated movement disorders. First identified through clinical studies in patients and families with GD, mutations in GBA1 are the most significant genetic risk factor for PD and associated neurodegenerative disorders, including dementia with Lewy bodies and rapid eye movements sleep behavior disorders (Sidransky et al., 2009; Sidransky and Lopez, 2012; Honeycutt et al., 2019). This discovery has directed increased attention to lysosomal dysfunction in PD pathogenesis, rendering glucocerebrosidase (GCase), the enzyme encoded by GBA1, an attractive target for therapeutic development, as recently reviewed by Chen et al. (2020).