Antioxidant Nanoparticles for Concerted Inhibition of α-Synuclein Fibrillization, and Attenuation of Microglial Intracellular Aggregation and Activation
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
References
Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs
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Alpha-Synuclein Aggregation (MDS)
Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.
Alpha-Synuclein Aggregation
Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.