CD36‐Binding Amphiphilic Nanoparticles for Attenuation of α‐Synuclein‐Induced Microglial Activation

Neuroinflammation is one of the hallmarks contributing to Parkinson's disease (PD) pathology, where microglial activation occurs as one of the earliest events, triggered by extracellular α‐synuclein (aSYN) binding to the cluster of differentation 36 (CD36) receptor. Herein, CD36‐binding nanoparticles (NPs) containing tartaric acid–based amphiphilic macromolecules (AMs) are rationally designed to inhibit this aSYN–CD36 binding. In silico docking reveals that four AMs with varying alkyl side chain lengths present differential levels of CD36 binding affinity and that an optimal alkyl chain length promotes the strongest inhibitory activity toward aSYN–CD36 interactions. In vitro competitive binding assays indicate that the inhibitory activity of AM‐based NPs plateaus at intermediate side chain lengths of 12 and 18 carbons, supporting the in silico docking predictions. These intermediate‐length AM NPs also has significantly stronger effects on reducing aSYN internalization and inhibiting proinflammatory molecules tumor necrosis factor α (TNF‐α) and nitric oxide from aSYN‐challenged microglia. All four NPs modulate the gene expression of aSYN‐challenged microglia, downregulating proinflammatory genes TNF, interleukin 6 (IL‐6), and IL‐1β, and upregulating anti‐inflammatory genes transforming growth factor β (TGF‐β) and Arg1 expression. Herein, overall, a novel polymeric nanotechnology platform is represented that can be used to modulate aSYN‐induced microglial activation.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
CD36‐Binding Amphiphilic Nanoparticles for Attenuation of α‐Synuclein‐Induced Microglial Activation ; day:22 ; month:03 ; year:2022 ; extent:12
Advanced nanoBiomed research ; (22.03.2022) (gesamt 12)

Urheber
Zhao, Nanxia
Francis, Nicola L.
Song, Shuang
Kholodovych, Vladyslav
Calvelli, Hannah R.
Hoop, Cody L.
Pang, Zhiping P.
Baum, Jean
Uhrich, Kathryn E.
Moghe, Prabhas V.

DOI
10.1002/anbr.202100120
URN
urn:nbn:de:101:1-2022032514350668374013
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:36 MESZ

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Beteiligte

  • Zhao, Nanxia
  • Francis, Nicola L.
  • Song, Shuang
  • Kholodovych, Vladyslav
  • Calvelli, Hannah R.
  • Hoop, Cody L.
  • Pang, Zhiping P.
  • Baum, Jean
  • Uhrich, Kathryn E.
  • Moghe, Prabhas V.

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