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Accelerating the clearance of mutant huntingtin protein aggregates through autophagy induction by europium hydroxide nanorods
- Wei, Peng-Fei, Zhang, Li, Nethi, Susheel Kumar, Barui, Ayan Kumar, Lin, Jun, Zhou, Wei, Shen, Yi, Man, Na, Zhang, Yun-Jiao, Xu, Jing, Patra, Chitta Ranjan, Wen, Long-Ping
- Biomaterials 2014 v.35 no.3 pp. 899-907
- autophagy, chloroquine, europium, human cell lines, lithium, mutants, nanomedicine, nanoparticles, nanorods, neurodegenerative diseases, protein aggregates, rapamycin, therapeutics, trehalose
- 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 [Euᴵᴵᴵ(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 [Euᴵᴵᴵ(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.