Getting cells to spit out clumped proteins

Several neurodegenerative diseases begin when toxic clumps of protein form in neurons. Scientists have yet to find a good way to clear these clumps from cells. Researchers now report that a small-molecule kinase inhibitor called apilimod can reduce neurotoxicity in cell and mouse models of amyotrophic lateral sclerosis (ALS) by forcing neurons to jettison aggregated proteins ( Cell 2023, DOI: 10.1016/j.cell.2023.01.005 ). The kinase that the molecule blocks, known as PIKFYVE , is the target of drug development efforts in at least three biotechnology companies. ALS is a rare neurodegenerative disease that currently affects an estimated 32,000 people in the US, according to the Centers for Disease Control and Prevention . The condition affects motor neurons; people with ALS lose mobility and, eventually, the ability to breathe. The impacted motor neurons often show aggregation of a protein called TDP-43. The protein plays an important role in producing and stabilizing RNA,