Receptor-targeting nanomaterials alleviate binge drinking-induced neurodegeneration as artificial neurotrophins

Bundled single-walled carbon nanotubes, as artificial neurotrophins, mediate dimerization and phosphorylation of tropomyosin-related kinase B, and stimulate downstream signaling pathways for neuronal survival and differentiation. These therapeutic effects alleviate EtOH-induced neurodegeneration in a rat model.

Abstract:

The distinguished properties of nanomaterials promote us to explore whether their intrinsic activities would be beneficial to disease treatment. Furthermore, understanding the molecular mechanism is thereby crucial for biomedical applications. Here, we investigate the therapeutic effects of single-walled carbon nanotubes (SWNTs) in a rat model of binge alcohol-induced neurodegeneration. With selection from four types of SWNT structures, bundled SWNTs (bSWNTs) facilitated the recovery of learning and memory via enhancing neuroprotection and neuroregeneration. We screened the potential target for bSWNTs, and found that bSWNTs have the abilities to directly interact with neurotrophic receptors, especially tropomyosin-related kinase B (TrkB). Moreover, similar to the actions of endogenous neurotrophins, bSWNTs could trigger the dimerization and phosphorylation of TrkB, while these conformational changes resulted in activating their downstream signals involved in neuroprotection and neuroregeneration. With relatively clear mechanisms, these “artificial neurotrophins” provide a proof-of-concept example as an efficiently therapeutic strategy for the treatment of neurodegenerative diseases.

Author list:

Jingyu Yang†, Lirong Wang†, Liwen Huang, Xiaohang Che, Zhen Zhang, Chunxiao Wang, Lihuan Bai, Ping Liu, Yanan Zhao, Xiaomei Hu, Bingyang Shi, Yuequan Shen, Xing-Jie Liang, Chunfu Wu*, Xue Xue*

How to cite:

J. Yang, L. Wang, L. Huang, X. Che, Z. Zhang, C. Wang, L. Bai, P. Liu, Y. Zhao, X. Hu, B. Shi, Y. Shen, X.-J. Liang, C. Wu, X. Xue, Exploration 2021, 1, 61-74.  https://doi.org/10.1002/EXP.20210004