title: Accelerating the clearance of mutant huntingtin protein aggregates through autophagy induction by europium hydroxide nanorods.
abstract: Autophagy is one of the well-known pathways to accelerate the clearance of protein aggregates, which contributes to the therapy of neurodegenerative diseases. Although there are numerous reports that demonstrate the induction of autophagy with small molecules including rapamycin, trehalose and lithium, however, there are few reports mentioning the clearance of aggregate-prone proteins through autophagy induction by nanoparticles. In the present article, we have demonstrated that europium hydroxide [Eu(III)(OH)3] nanorods can reduce huntingtin protein aggregation (EGFP-tagged huntingtin protein with 74 polyQ repeats), responsible for neurodegenerative diseases. Again, we have found that these nanorods induce authentic autophagy flux in different cell lines (Neuro 2a, PC12 and HeLa cells) through the expression of higher levels of characteristic autophagy marker protein LC3-II and degradation of selective autophagy substrate/cargo receptor p62/SQSTM1. Furthermore, depression of protein aggregation clearance through the autophagy blockade has also been observed by using specific inhibitors (wortmannin and chloroquine), indicating that autophagy is involved in the degradation of huntingtin protein aggregation. Since [Eu(III)(OH)3] nanorods can enhance the degradation of huntingtin protein aggregation via autophagy induction, we strongly believe that these nanorods would be useful for the development of therapeutic treatment strategies for various neurodegenerative diseases in near future using nanomedicine approach.
authors.affiliation: Hefei National Laboratory for Physical Sciences at The Microscale, School of Life Sciences, University of Science and Technology of China, 230027 Hefei, PR China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Susheel Kumar
authors.initials: SK
authors.lastname: Nethi
authors.forename: Ayan Kumar
authors.initials: AK
authors.lastname: Barui
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.forename: Na
authors.initials: N
authors.lastname: Man
authors.forename: Yun-Jiao
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Chitta Ranjan
authors.initials: CR
authors.lastname: Patra
authors.forename: Long-Ping
authors.initials: LP
authors.lastname: Wen
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D005063:Europium / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D000071058:Huntingtin Protein; D006878:Hydroxides / Q000737:chemistry / Q000494:pharmacology*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D006878:Hydroxides; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D005063:Europium; C031356:hydroxide ion
keywords: Autophagy; Chloroquine (CQ); Europium hydroxide [Eu(III)(OH)(3)] nanorods; Huntingtin aggregation; Nanomedicine