The role of TDP-43 propagation in neurodegenerative diseases: integrating insights from clinical and experimental studies

• Main Authors: Myungjin Jo, Shinrye Lee, Yu-Mi Jeon, Seyeon Kim, Younghwi Kwon, Hyung-Jun Kim
• Format: Article
• Language: English
• Published: Nature Publishing Group 2020-10-01
• Series: Experimental and Molecular Medicine
• Online Access: https://doi.org/10.1038/s12276-020-00513-7
• ISSN: 1226-3613; 2092-6413

Neurodegenerative disorders: Spread of misfolded protein aggregates Further research is needed to determine how an aggregate-forming protein common to several neurodegenerative disorders propagates throughout the brain. Many neurodegenerative conditions involve aggregates created by ‘prion-like’ proteins, misfolded proteins that can confer their abnormal structure on neighboring healthy proteins, resulting in aggregates which spread rather like an infection. Hyung-Jun Kim at the Korea Brain Research Institute in Daegu, South Korea, and co-workers reviewed current understanding of the transactive response DNA-binding protein 43 (TDP-43), an aggregate-forming protein implicated in disorders such as Alzheimer’s disease and frontotemporal dementia. Growing evidence suggests that TDP-43 may spread in a prion-like fashion. TDP-43 is implicated in the onset of Alzheimer’s, and the spread of misfolded TDP-43 aggregates is closely tied to disease severity. More research is needed into how TDP-43 propagates in different tissues and central nervous system cells.