Research Roundup: January 18, 2019

Probing microtubules' part in ALS, and investigating a herbicide's inflammatory properties.

Erik Jacobs
Credit: Erik Jacobs

Welcome to the January 18, 2019 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

Microtubule mediator might mend motor neurons

The role of RNA metabolism and the RNA-binding TDP-43 protein in amyotrophic lateral sclerosis (ALS) is a little clearer after a new study led by institute member Kevin Eggan of Harvard and the Stanley Center for Psychiatric Research, Joseph Klim, and Luis Williams. They found that TDP-43 depletion in human motor neurons alters RNA transcript levels of some proteins, notably, the microtubule regulator STMN2. The researchers showed that STMN2 is necessary for normal growth and regeneration of axons, and that stabilizing it post-translationally restored the deficits due to TDP-43 depletion. Reporting in Nature Neuroscience, the scientists suggest that boosting STMN2 expression could be a potential strategy for treating ALS.

Herbicide linked to neurological disease risk

Both genes and environment cause disease risk, but most comprehensive methods have focused on studying the effects of genes rather than those of the environment. Associate member Francisco Quintana and colleagues investigated the effects of environmental factors on neurological diseases. Using bioinformatic and zebrafish models, the researchers screened 976 chemicals to identify compounds that affect signaling pathways linked to multiple sclerosis. They further studied the effects of five shortlisted compounds on neurological inflammation, confirming in mouse cells that the herbicide linuron can increase inflammation. The findings provide insights about a novel neurodegeneration pathway and therapeutic targets, and may also guide future epidemiological studies to identify disease-related environmental factors. Read more in Cell and in a Brigham and Women's Hospital press release.

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