Kinase inhibitor makes neurons release toxic protein aggregates
Researchers, biotech companies hope to use finding to treat ALS
Several neurodegenerative diseases begin when toxic protein clumps 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 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 targets, known as PIKFYVE, is the target of drug-development efforts in at least three biotechnology companies.
ALS is a rare neurodegenerative disease that affects an estimated 32,000 people in the US according to the Centers for Disease Control. The deadly disease affects motor neurons; people with ALS lose mobility and, eventually, the ability to breathe. Those affected motor neurons often show aggregation of a protein called TDP-43. The protein plays an important role in producing and stabilizing RNA, but when it misfolds and clumps together, it can kill cells. In the same way, other proteins can aggregate and kill neurons in Parkinson’s or Alzheimer’s diseases.