4.7 Article

Thoracic trauma promotes alpha-Synuclein oligomerization in murine Parkinson's disease

期刊

NEUROBIOLOGY OF DISEASE
卷 174, 期 -, 页码 -

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2022.105877

关键词

Alpha synuclein; Trauma; Inflammation; Parkinson ?s disease; Peripheral lesion

资金

  1. Deutsche Forschungsgemeinschaft (DFG) Emmy Noether Research Group [DA 1657/2-1, GRK 1789]
  2. Deutsche Forschungsgemeinschaft as part of the Collaborative Research Center 1149 Danger Response, Disturbance Factors and Regenerative Potential after Acute Trauma (DFG) [251293561]

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This study provides evidence that physical trauma is associated with increased asyn oligomerization in a PD mouse model, highlighting the relevance of PD pathogenesis under traumatic settings.
Background: Systemic and neuroinflammatory processes play key roles in neurodegenerative diseases such as Parkinson's disease (PD). Physical trauma which induces considerable systemic inflammatory responses, rep-resents an evident environmental factor in aging. However, little is known about the impact of physical trauma, on the immuno-pathophysiology of PD. Especially blunt chest trauma which is associated with a high morbidity and mortality rate in the elderly population, can induce a strong pulmonary and systemic inflammatory reaction. Hence, we sought out to combine a well-established thoracic trauma mouse model with a well-established PD mouse model to characterize the influence of physical trauma to neurodegenerative processes in PD. Methods: To study the influence of peripheral trauma in a PD mouse model we performed a highly standardized blunt thorax trauma in a well-established PD mouse model and determined the subsequent local and systemic response. Results: We could show that blunt chest trauma leads to a systemic inflammatory response which is quantifiable with increased inflammatory markers in bronchoalveolar fluids (BALF) and plasma regardless of the presence of a PD phenotype. A difference of the local inflammatory response in the brain between the PD group and non-PD group could be detected, as well as an increase in the formation of oligomeric pathological alpha-Synuclein (asyn) suggesting an interplay between peripheral thoracic trauma and asyn pathology in PD. Conclusion: Taken together this study provides evidence that physical trauma is associated with increased asyn oligomerization in a PD mouse model underlining the relevance of PD pathogenesis under traumatic settings.

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