Antioxidant Nanoparticles for Concerted Inhibition of α-Synuclein Fibrillization, and Attenuation of Microglial Intracellular Aggregation and Activation

Frontiers in Bioengineering and Biotechnology
Nanxia ZhaoPrabhas V Moghe

Abstract

Parkinson's Disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, the extracellular accumulation of toxic α-synuclein (αSYN) aggregates, and neuroinflammation. Microglia, resident macrophages of the brain, are one of the critical cell types involved in neuroinflammation. Upon sensing extracellular stimuli or experiencing oxidative stress, microglia become activated, which further exacerbates neuroinflammation. In addition, as the first line of defense in the central nervous system, microglia play a critical role in αSYN clearance and degradation. While the role of microglia in neurodegenerative pathologies is widely recognized, few therapeutic approaches have been designed to target both microglial activation and αSYN aggregation. Here, we designed nanoparticles (NPs) to deliver aggregation-inhibiting antioxidants to ameliorate αSYN aggregation and attenuate activation of a pro-inflammatory microglial phenotype. Ferulic acid diacid with an adipic acid linker (FAA) and tannic acid (TA) were used as shell and core molecules to form NPs via flash nanoprecipitation. These NPs showed a strong inhibitory effect on αSYN fibrillization, significantly diminishing αSYN fibrillization in vitro...Continue Reading

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Citations

Sep 20, 2020·Biomolecules·Loredana LeggioNunzio Iraci
Sep 15, 2020·APL Bioengineering·Nanxia ZhaoPrabhas V Moghe
May 15, 2021·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Neeraja Revi, Aravind Kumar Rengan
Sep 4, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Thuy Trang NguyenGiau Van Vo

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Methods Mentioned

BETA
nanoprecipitation
ELISA
nuclear translocation
acetylation
nuclear
confocal

Software Mentioned

NIH
GraphPad Prism
ImageJ

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Alpha-Synuclein Aggregation

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