Download
s12974-023-02830-w.pdf 4,09MB
WeightNameValue
1000 Titel
  • Pharmacologic inhibition of NLRP3 reduces the levels of α-synuclein and protects dopaminergic neurons in a model of Parkinson’s disease
1000 Autor/in
  1. Amo-Aparicio, Jesus |
  2. Daly, Jonathan |
  3. Højen, Jesper Fal |
  4. Dinarello, Charles A. |
1000 Erscheinungsjahr 2023
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2023-06-22
1000 Erschienen in
1000 Quellenangabe
  • 20(1):147
1000 Copyrightjahr
  • 2023
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1186/s12974-023-02830-w |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10286423/ |
1000 Ergänzendes Material
  • https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-023-02830-w#Sec25 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • BACKGROUND: Parkinson’s disease (PD) is characterized by a progressive degeneration of dopaminergic neurons, which leads to irreversible loss of peripheral motor functions. Death of dopaminergic neurons induces an inflammatory response in microglial cells, which further exacerbates neuronal loss. Reducing inflammation is expected to ameliorate neuronal loss and arrest motor dysfunctions. Because of the contribution of the NLRP3 inflammasome to the inflammatory response in PD, we targeted NLRP3 using the specific inhibitor OLT1177®. METHODS: We evaluated the effectiveness of OLT1177® in reducing the inflammatory response in an MPTP neurotoxic model of PD. Using a combination of in vitro and in vivo studies, we analyzed the effects of NLRP3 inhibition on pro-inflammatory markers in the brain, α-synuclein aggregation, and dopaminergic neuron survival. We also determined the effects of OLT1177® on locomotor deficits associated with MPTP and brain penetrance. RESULTS: Treatment with OLT1177® prevented the loss of motor function, reduced the levels of α-synuclein, modulated pro-inflammatory markers in the nigrostriatal areas of the brain, and protected dopaminergic neurons from degeneration in the MPTP model of PD. We also demonstrated that OLT1177® crosses the blood–brain barrier and reaches therapeutic concentrations in the brain. CONCLUSIONS: These data suggest that targeting the NLRP3 inflammasome by OLT1177® may be a safe and novel therapeutic approach to arrest neuroinflammation and protect against neurological deficits of Parkinson’s disease in humans.
1000 Sacherschließung
lokal NLRP3
lokal α-synuclein
lokal OLT1177
lokal Inflammasome
lokal Parkinson's disease
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/QW1vLUFwYXJpY2lvLCBKZXN1cw==|https://frl.publisso.de/adhoc/uri/RGFseSwgSm9uYXRoYW4=|https://frl.publisso.de/adhoc/uri/SMO4amVuLCBKZXNwZXIgRmFs|https://frl.publisso.de/adhoc/uri/RGluYXJlbGxvLCBDaGFybGVzIEEu
1000 Label
1000 Förderer
  1. National Institutes of Health |
1000 Fördernummer
  1. AI-15614
1000 Förderprogramm
  1. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer National Institutes of Health |
    1000 Förderprogramm -
    1000 Fördernummer AI-15614
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6453080.rdf
1000 Erstellt am 2023-07-10T09:04:06.625+0200
1000 Erstellt von 337
1000 beschreibt frl:6453080
1000 Bearbeitet von 317
1000 Zuletzt bearbeitet 2023-08-04T10:49:15.038+0200
1000 Objekt bearb. Fri Aug 04 10:49:01 CEST 2023
1000 Vgl. frl:6453080
1000 Oai Id
  1. oai:frl.publisso.de:frl:6453080 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

View source