Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387564325> ?p ?o ?g. }
- W4387564325 endingPage "114069" @default.
- W4387564325 startingPage "114069" @default.
- W4387564325 abstract "Parkinson's disease (PD) is characterized by motor impairments and progressive dopaminergic neuronal death in the substantia nigra (SN). Recently, the involvement of other regulated cell death (RCD) machineries has been highlighted in PD. Necroptosis is controlled by p-RIPK1, p-RIPK3, and p-MLKL and negatively regulated by caspase-8. Ferroptosis is characterized by iron overload and accumulation of reactive oxygen species. Interestingly, the molecular chaperone complex HSP90/CDC37 has been reported to directly regulate necroptosis, ferroptosis, and some PD-associated proteins. We investigated the potential anti-necroptotic and anti-ferroptotic effects of the anti-cancer drug pazopanib, uncovering the HSP90/CDC37 complex as a master RCD modulator in rotenone-induced Parkinsonism in rats. Oral administration of 15 mg/kg pazopanib to rotenone-intoxicated rats for three weeks improved motor deficits, debilitated histopathological changes, and increased striatal dopaminergic levels. Pazopanib suppressed LRRK2 and c-Abl. Pazopanib displayed an anti-necroptotic effect through inhibition of the p-RIPK1/p-RIPK3/p-MLKL pathway and activation of caspase-8. Moreover, pazopanib inhibited the ferroptotic p-VEGFR2-PKCβII-PLC-γ-ACSL-4 pathway, iron, 4-HNE, and PTGS2 while increasing GPX-4 and GSH levels. Taken together, the current research sheds light on the repositioning of pazopanib targeting HSP90/CDC37 and its multiple RCD mechanisms, which would offer a new perspective for therapeutic strategies in PD." @default.
- W4387564325 created "2023-10-13" @default.
- W4387564325 creator A5050111038 @default.
- W4387564325 creator A5060731354 @default.
- W4387564325 creator A5073244900 @default.
- W4387564325 creator A5083261947 @default.
- W4387564325 date "2023-11-01" @default.
- W4387564325 modified "2023-10-18" @default.
- W4387564325 title "Pazopanib ameliorates rotenone-induced Parkinsonism in rats by suppressing multiple regulated cell death mechanisms" @default.
- W4387564325 cites W1567934634 @default.
- W4387564325 cites W1612435886 @default.
- W4387564325 cites W1964717422 @default.
- W4387564325 cites W1966977448 @default.
- W4387564325 cites W1978793506 @default.
- W4387564325 cites W1979032223 @default.
- W4387564325 cites W1997183854 @default.
- W4387564325 cites W2003945664 @default.
- W4387564325 cites W2004585452 @default.
- W4387564325 cites W2009294443 @default.
- W4387564325 cites W2020259214 @default.
- W4387564325 cites W2021861995 @default.
- W4387564325 cites W2021899761 @default.
- W4387564325 cites W2021935429 @default.
- W4387564325 cites W2021976306 @default.
- W4387564325 cites W2045497115 @default.
- W4387564325 cites W2046525214 @default.
- W4387564325 cites W2052098570 @default.
- W4387564325 cites W2059577301 @default.
- W4387564325 cites W2069884615 @default.
- W4387564325 cites W2085945766 @default.
- W4387564325 cites W2086435172 @default.
- W4387564325 cites W2110796758 @default.
- W4387564325 cites W2117692326 @default.
- W4387564325 cites W2119028277 @default.
- W4387564325 cites W2127447993 @default.
- W4387564325 cites W2128247060 @default.
- W4387564325 cites W2129375925 @default.
- W4387564325 cites W2130356495 @default.
- W4387564325 cites W2130407823 @default.
- W4387564325 cites W2133079836 @default.
- W4387564325 cites W2158662692 @default.
- W4387564325 cites W2189205651 @default.
- W4387564325 cites W2281483133 @default.
- W4387564325 cites W2291832556 @default.
- W4387564325 cites W2297563545 @default.
- W4387564325 cites W231086871 @default.
- W4387564325 cites W2313426974 @default.
- W4387564325 cites W2331898099 @default.
- W4387564325 cites W2374069442 @default.
- W4387564325 cites W2418456889 @default.
- W4387564325 cites W2511018985 @default.
- W4387564325 cites W2513656923 @default.
- W4387564325 cites W2522646258 @default.
- W4387564325 cites W2537961007 @default.
- W4387564325 cites W2549188196 @default.
- W4387564325 cites W2556383989 @default.
- W4387564325 cites W2584580415 @default.
- W4387564325 cites W2753051298 @default.
- W4387564325 cites W2768455179 @default.
- W4387564325 cites W2793585691 @default.
- W4387564325 cites W2806157958 @default.
- W4387564325 cites W2851271116 @default.
- W4387564325 cites W2896065796 @default.
- W4387564325 cites W2904244708 @default.
- W4387564325 cites W2912822929 @default.
- W4387564325 cites W2912997981 @default.
- W4387564325 cites W2938325670 @default.
- W4387564325 cites W2981900312 @default.
- W4387564325 cites W2990759755 @default.
- W4387564325 cites W3010750273 @default.
- W4387564325 cites W3016093449 @default.
- W4387564325 cites W3127978442 @default.
- W4387564325 cites W3135042121 @default.
- W4387564325 cites W3158344187 @default.
- W4387564325 cites W3167562979 @default.
- W4387564325 cites W3170954603 @default.
- W4387564325 cites W4200163540 @default.
- W4387564325 cites W4205704013 @default.
- W4387564325 cites W4282593751 @default.
- W4387564325 cites W4282946416 @default.
- W4387564325 cites W4293860078 @default.
- W4387564325 cites W4313594841 @default.
- W4387564325 cites W4382404999 @default.
- W4387564325 doi "https://doi.org/10.1016/j.fct.2023.114069" @default.
- W4387564325 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37820786" @default.
- W4387564325 hasPublicationYear "2023" @default.
- W4387564325 type Work @default.
- W4387564325 citedByCount "0" @default.
- W4387564325 crossrefType "journal-article" @default.
- W4387564325 hasAuthorship W4387564325A5050111038 @default.
- W4387564325 hasAuthorship W4387564325A5060731354 @default.
- W4387564325 hasAuthorship W4387564325A5073244900 @default.
- W4387564325 hasAuthorship W4387564325A5083261947 @default.
- W4387564325 hasConcept C121608353 @default.
- W4387564325 hasConcept C126322002 @default.
- W4387564325 hasConcept C137183658 @default.
- W4387564325 hasConcept C169760540 @default.
- W4387564325 hasConcept C185592680 @default.