期刊
NEUROBIOLOGY OF DISEASE
卷 159, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2021.105511
关键词
Dystonia; Second hit; Pathophysiology; Gene-environment interaction
资金
- Interdisciplinary Center for Clinical Research (IZKF) at the University of Wurzburg [Z2-CSP3]
- Dystonia Medical Research Foundation in Illinois, USA (Postdoctoral Research Fellowship Award)
- Federal ministry of Education and Research in Germany (BMBF DYSTRACT)
- German Research Foundation (DFG) [424778381-TRR 295]
- VERUM Foundation
- German Research Foundation (DFG)
- European Joint Programme on Rare Diseases
- Italian Ministry of Health
- European Joint Programme on Rare Diseases [EJP RD-135 2019]
- European Union [825575]
- NINDS Intramural Program
- Open Access Publication Fund of the University of Wuerzburg
The role of environmental factors in dystonia onset and development, especially in monogenic and adult-onset dystonia, remains a mystery in dystonia pathophysiology. Evidence suggests a gene-environment interaction, but the specific mechanisms are still unclear.
One of the great mysteries in dystonia pathophysiology is the role of environmental factors in disease onset and development. Progress has been made in defining the genetic components of dystonic syndromes, still the mechanisms behind the discrepant relationship between dystonic genotype and phenotype remain largely unclear. Within this review, the preclinical and clinical evidence for environmental stressors as disease modifiers in dystonia pathogenesis are summarized and critically evaluated. The potential role of extragenetic factors is discussed in monogenic as well as adult-onset isolated dystonia. The available clinical evidence for a second hit is analyzed in light of the reduced penetrance of monogenic dystonic syndromes and put into context with evidence from animal and cellular models. The contradictory studies on adult-onset dystonia are discussed in detail and backed up by evidence from animal models. Taken together, there is clear evidence of a gene-environment interaction in dystonia, which should be considered in the continued quest to unravel dystonia pathophysiology.
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