Research Highlight

Molecule promise for amyotrophic lateral sclerosis 

doi:10.1038/nindia.2020.26 Published online 12 February 2020

A newly identified molecule ‘AIM4’ holds potential in stopping the degeneration of nerves in the neurological disease amyotrophic lateral sclerosis (ALS)1.

Researchers from the Indian Institute of Technology in Hyderabad, who worked on a computer model system that mimics the development of ALS, say the molecule could offer a promising treatment for the disease.

ALS mainly destroys nerve cells involved in controlling the movement of voluntary muscles that help in chewing, walking and talking. The disease occurs because of mutations in a gene that encodes a DNA-binding protein called TDP-43. Such mutations cause this protein to misfold and form nerve-cell-destroying protein clumps. Currently, there are no drugs to halt or reverse such process in ALS.

The scientists, led by Basant Kumar Patel and Ganesan Prabushankar, found that AIM4 inhibited the aggregation of TDP-43 in nerve cells. They detected that the molecule halted a specific process known as protein-phase separation, which sets off the formation of protein clumps in nerve cells.

AIM4, they report, was better than other molecules previously studied for the treatment of nerve disorders. With the help of computer models, they demonstrated that AIM4 bound to a specific site on TDP-43, eventually blocking its deposition in nerve cells.

AIM4 could also be promising in the treatment of other neurodegenerative diseases, they say.  



1. Girdhar, A. et al. Computational insights into mechanism of AIM4-mediated inhibition of aggregation of TDP-43 protein implicated in ALS and evidence for in vitro inhibition of liquid-liquid phase separation (LLPS) of TDP-432C-A315T by AIM4. Int. J. Biol. Macromol. 147,117-130 (2020)