Prospects of Directly Reprogrammed Adult Human Neurons for Neurodegenerative Disease Modeling and Drug Discovery: iN vs. iPSCs Models

Ying Zhang; Xinyang Xie; Jiangnan Hu; Kazi Sabrina Afreen; Chun-Li Zhang; Qichuan Zhuge; Jianjing Yang

doi:10.3389/fnins.2020.546484

Prospects of Directly Reprogrammed Adult Human Neurons for Neurodegenerative Disease Modeling and Drug Discovery: iN vs. iPSCs Models

Front Neurosci. 2020 Nov 19:14:546484. doi: 10.3389/fnins.2020.546484. eCollection 2020.

Authors

Ying Zhang^{1

2}, Xinyang Xie^{1

2

3}, Jiangnan Hu⁴, Kazi Sabrina Afreen⁵, Chun-Li Zhang⁶, Qichuan Zhuge^{1

2}, Jianjing Yang^{1

2}

Affiliations

¹ Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
³ International Department of The Affiliated High School of South China Normal University (HFI), Guangzhou, China.
⁴ Department of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, TX, United States.
⁵ Department of Microbiology & Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United States.
⁶ Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, United States.

Abstract

A reliable disease model is critical to the study of specific disease mechanisms as well as for the discovery and development of new drugs. Despite providing crucial insights into the mechanisms of neurodegenerative diseases, translation of this information to develop therapeutics in clinical trials have been unsuccessful. Reprogramming technology to convert adult somatic cells to induced Pluripotent Stem Cells (iPSCs) or directly reprogramming adult somatic cells to induced Neurons (iN), has allowed for the creation of better models to understand the molecular mechanisms and design of new drugs. In recent times, iPSC technology has been commonly used for modeling neurodegenerative diseases and drug discovery. However, several technological challenges have limited the application of iN. As evidence suggests, iN for the modeling of neurodegenerative disorders is advantageous compared to those derived from iPSCs. In this review, we will compare iPSCs and iN models for neurodegenerative diseases and their potential applications in the future.

Keywords: disease modeling; drug screening; iN; iPSCs; neurodegenerative disease.

Publication types

Review