Blog – Page 9

Though protein clumps associated with Alzheimer’s and Parkinson’s were discovered more than a century ago, researchers remain largely unable to prevent them from forming or eliminate them from the brain. And though a variety of therapies have taken aim at tau tangles, beta-amyloid plaques and Lewy bodies, among other notorious aggregates, none have been very effective at stopping disease progression.

Rockefeller’s Hermann Steller and his team in the Strang Laboratory of Apoptosis and Cancer Biology have long been focused on understanding how the cell’s protein-degrading machines, called proteasomes, are regulated. His lab discovered that a transporter protein termed PI31 shuttles proteasomes over long distances from the nerve cell body to synapses. When this system fails, synapses become depleted of degradative capacity, and proteins that should have been eliminated accumulate. As a result, synaptic communication breaks down, protein clumps form and neuronal health deteriorates.

Now a new study in Nature Communications, led by researchers from University College London and contributed to by Steller’s lab, has identified mutations in PSMF1, the gene that produces PI31, that cause the protein to malfunction. Moreover, the scientists demonstrated that these mutations cause a spectrum of severe, very early-onset neurological disorders.