Ucl queen square institute of neurology and uk dementia research institute, Institute

ALS is a neurodegenerative disorder that severely affects voluntary movement of muscles and can lead to paralysis and death. It occurs due to changes in specific genes, which may be triggered by factors such as smoking, exposure to toxins, metals and pesticides.The results of this research has recently been published in International Journal of Biological Macromolecules.According to the Institute, there are no drugs available at present to cure ALS and treatment options are limited to two drugs only for management of the condition."One of the causes of ALS is the alterations in the genes that code for a critical protein called TDP-43. The gene alteration modifies the protein, which results in its liquid-liquid phase separation. This phase separation in turn causes the proteins to be deposited on nerve cells, resulting in neurodegeneration," said study researcher Basant Kumar Patel, Associate Professor, Department of Biotechnology, IIT Hyderabad.In 2016, Patel and his team found a small molecule called 'AIM4,' which seemed to be better than the other related molecules that have been studied all around the world, in its ability to inhibit abnormal aggregation of TDP-43 in vitro ALS disease model systems.With this knowledge, the IIT-H scientists proceeded to analyse this molecule and study its action on TDP-43, to predict how it would potentially inhibit the deposition of the protein in nerve cells."We have shown that AIM4 prevents liquid-liquid phase separation of the modified protein, TDP-43-A315T. By this, AIM4 prevents aggregation of the protein and may potentially prevent the deposition on neurons," Patel said.The research group compared the ability of AIM4 to prevent protein phase separation with that of other molecules such as Dimebon.Dimebon is an antihistamine that was studied for treatment of neurodegenerative disorders by an American pharmaceutical company but failed clinical trials.The team found that AIM4 was better than such earlier molecules in preventing protein phase separation.The research team has also discovered through computational studies that AIM4 has specific binding site on this protein and binding energy calculations have shown that the bond between AIM4 and the mutant protein is energetically favourable, which makes it a promising drug for potential treatment of ALS.( With inputs from IANS )

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