Matches in SemOpenAlex for { <https://semopenalex.org/work/W3036742750> ?p ?o ?g. }
Showing items 1 to 55 of
55
with 100 items per page.
- W3036742750 abstract "Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease affecting approximately 1 % of the population above 60 years of age. It affects preferentially the extrapyramidal system, causing severe deficits in motor function. So far, the progression of the disease can neither be delayed nor cured. The dyshomeostasis of trace elements, especially of iron, and the presence of alpha-synuclein (α-syn) aggregate-containing Lewy bodies (LBs) in the brain are two main pathologic events playing a crucial role in PD. The underlying pathomechanisms for spreading of α-syn through the brain are still unknown, but PD-related targets such as trace elements or the rho-associated protein kinase (ROCK) were suggested to affect its aggregation pathology. Identifying triggers that affect α-syn propagation is of fundamental importance since they could be considered as auspicious targets for new therapeutic strategies. In the present study, the elemental content of nigral neurons of PD patients and control patients without neurodegeneration was analyzed using X-ray fluorescence (XRF) and it was found that intracellular element concentrations differ substantially within and between patients. Copper was the most discriminating element between the groups. On a subcellular level, X-ray diffraction revealed the presence of β-sheet protein structures in a LB, whereas XRF measurements identified a varying distribution of trace elements such as iron, selenium or copper within two LBs. Furthermore, the relation of iron and α-syn was examined. With the objective to investigate the influence of iron on α-syn propagation through the brain, a murine α-syn fibrils injection model was combined with iron intoxication and revealed reducing and redistribution effects of iron on α-syn spreading and a reduced microglia accumulation. Both iron and α-syn fibrils treatment resulted in long-term memory dysfunction in the novel object recognition test. Moreover, the influence of iron on α-syn spreading was investigated in cortical neurons using microfluidic chambers. Spreading of α-syn seemed not to be affected by iron in vitro, arguing for a more systemic mode of action in vivo. Since the ROCK inhibitor fasudil showed multiple protective effects in PD mouse models previously, we analyzed its effects on α-syn spreading in vivo. Here, the application of fasudil did not alter α-syn propagation. Taken together, the present work investigates the influence of trace elements, particularly iron, and ROCK inhibition on α-syn spreading and thus contributes to a better understanding of PD pathophysiology and to the identification of auspicious targets for new therapeutic strategies." @default.
- W3036742750 created "2020-06-25" @default.
- W3036742750 creator A5057435795 @default.
- W3036742750 date "2022-02-21" @default.
- W3036742750 modified "2023-10-03" @default.
- W3036742750 title "Alpha-synuclein spreading pathology in Parkinson's disease: the influence of iron and the Rho-kinase inhibitor fasudil" @default.
- W3036742750 doi "https://doi.org/10.53846/goediss-8016" @default.
- W3036742750 hasPublicationYear "2022" @default.
- W3036742750 type Work @default.
- W3036742750 sameAs 3036742750 @default.
- W3036742750 citedByCount "0" @default.
- W3036742750 crossrefType "dissertation" @default.
- W3036742750 hasAuthorship W3036742750A5057435795 @default.
- W3036742750 hasBestOaLocation W30367427501 @default.
- W3036742750 hasConcept C142724271 @default.
- W3036742750 hasConcept C169760540 @default.
- W3036742750 hasConcept C185592680 @default.
- W3036742750 hasConcept C2776925932 @default.
- W3036742750 hasConcept C2779134260 @default.
- W3036742750 hasConcept C2779734285 @default.
- W3036742750 hasConcept C2781449126 @default.
- W3036742750 hasConcept C2908647359 @default.
- W3036742750 hasConcept C71924100 @default.
- W3036742750 hasConcept C86803240 @default.
- W3036742750 hasConcept C95444343 @default.
- W3036742750 hasConcept C99454951 @default.
- W3036742750 hasConceptScore W3036742750C142724271 @default.
- W3036742750 hasConceptScore W3036742750C169760540 @default.
- W3036742750 hasConceptScore W3036742750C185592680 @default.
- W3036742750 hasConceptScore W3036742750C2776925932 @default.
- W3036742750 hasConceptScore W3036742750C2779134260 @default.
- W3036742750 hasConceptScore W3036742750C2779734285 @default.
- W3036742750 hasConceptScore W3036742750C2781449126 @default.
- W3036742750 hasConceptScore W3036742750C2908647359 @default.
- W3036742750 hasConceptScore W3036742750C71924100 @default.
- W3036742750 hasConceptScore W3036742750C86803240 @default.
- W3036742750 hasConceptScore W3036742750C95444343 @default.
- W3036742750 hasConceptScore W3036742750C99454951 @default.
- W3036742750 hasLocation W30367427501 @default.
- W3036742750 hasOpenAccess W3036742750 @default.
- W3036742750 hasPrimaryLocation W30367427501 @default.
- W3036742750 hasRelatedWork W10866912 @default.
- W3036742750 hasRelatedWork W1369830 @default.
- W3036742750 hasRelatedWork W2439058 @default.
- W3036742750 hasRelatedWork W2523290 @default.
- W3036742750 hasRelatedWork W2824068 @default.
- W3036742750 hasRelatedWork W372785 @default.
- W3036742750 hasRelatedWork W386916 @default.
- W3036742750 hasRelatedWork W5285369 @default.
- W3036742750 hasRelatedWork W7129343 @default.
- W3036742750 hasRelatedWork W762776 @default.
- W3036742750 isParatext "false" @default.
- W3036742750 isRetracted "false" @default.
- W3036742750 magId "3036742750" @default.
- W3036742750 workType "dissertation" @default.