Polymer brain-nanotherapeutics for multipronged inhibition of microglial α-synuclein aggregation, activation, and neurotoxicity.

ABSTRACT: Neuroinflammation, a common neuropathologic feature of neurodegenerative disorders including Parkinson disease (PD), is frequently exacerbated by microglial activation. The extracellular protein α-synuclein (ASYN), whose aggregation is characteristic of PD, remains a key therapeutic target, but the control of synuclein trafficking and aggregation within microglia has been challenging. First, we established that microglial internalization of monomeric ASYN was mediated by scavenger receptors (SR), CD36 and SRA1, and was rapidly accompanied by the formation of ASYN oligomers. Next, we designed a nanotechnology approach to regulate SR-mediated intracellular ASYN trafficking within microglia. We synthesized mucic acid-derivatized sugar-based amphiphilic molecules (AM) with optimal stereochemis

SUBMITTER: Bennett NK 

PROVIDER: S-EPMC5262519 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature