Second hit hypothesis in dystonia: Dysfunctional cross talk between neuroplasticity and environment?
Please always quote using this URN: urn:nbn:de:bvb:20-opus-265028
- 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 isOne 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.…
Author: | Lisa Rauschenberger, Susanne Knorr, Antonio Pisani, Mark Hallett, Jens Volkmann, Chi Wang Ip |
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URN: | urn:nbn:de:bvb:20-opus-265028 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Neurologische Klinik und Poliklinik |
Language: | English |
Parent Title (English): | Neurobiology of Disease |
Year of Completion: | 2021 |
Volume: | 159 |
Article Number: | 105511 |
Source: | Neurobiology of Disease (2021) 159:105511. https://doi.org/10.1016/j.nbd.2021.105511 |
DOI: | https://doi.org/10.1016/j.nbd.2021.105511 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | dystonia; gene-environment interaction; pathophysiology; second hit |
Release Date: | 2022/04/28 |
EU-Project number / Contract (GA) number: | 825575 |
OpenAIRE: | OpenAIRE |
Collections: | Open-Access-Publikationsfonds / Förderzeitraum 2021 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |