EMBO J: New research could help treat Huntington's disease.

7, 2020 /--- -- In a recent study, scientists discovered that an enzyme called TBK1 plays a central role in regulating the degradation and removal of Huntington's protein.
is an ongoing brain disease that causes loss of movement, psychological problems and cognition.
it is a genetic mutation that encodes the protein Huntington's protein, which in turn prevents the huntingtin protein from folding properly, causing it to gather inside neurons in the brain and eventually leading to the death of neuron cells.
(Photo source: www.pixabay.com) Huntington's disease affects thousands of people around the world, and as an "autosomal-explicit genetic" disease, a person needs only one copy of the Huntington's mutation gene to develop the disease.
academic and industrial scientists are exploring solutions to the disease.
most popular strategy is to lower levels of huntingtin protein or inhibit its aggregation.
now, scientists at EPFL's Professor Hilal Lashuel laboratory have discovered a new enzyme that acts on both.
the enzyme, called TBK1, plays a central role in regulating the degradation and removal of Huntington's protein and has found chemical modifications that prevent it from aggregating.
in cells, kinases are enzymes that add phosphate groups to various biological molecules.
previous studies have shown that artificial addition of phosphate groups to huntingtin proteins can prevent them from aggregating and cause Huntington's disease.
researchers found that TBK1 inhibits its ability to aggregate when it is added anywhere in the first 17 amino acids of the Huntington's protein.
the normal and mutated forms of Huntington's protein.
addition, elevated TBK1 levels in cells can lead to excessive phosphorylation of certain amino acids (serine) in huntingtin proteins.
this stabilizes the protein and prevents it from aggregation.
, the authors also found that TBK1 sends signals that cells degrade and remove Huntington's protein before it gathers.
this reduces overall Huntington's protein levels, thereby reducing the formation of intracular aggregates.
inspired by their discovery, scientists later applied it to animal models of Huntington's disease.
they confirmed previous data: TBK1 kinase over-expression protects the mutant Huntington's protein toxicity in the worm and prevents the development of Huntington's disease.
researchers got similar results in cultured neurons.
(bioon.com) Source: Discovery Shows promise for Huntington's Disease Source: Ramanath Narayana Hegde, Anass Chiki, Lara Petricca, Paola Martufi, Nicolas Arbez, Laurent Mouchiroud, Johan Auwerx, Christian Landles, Gillian P Bates, Malvindar K Singh-Bains, Mike Dragunow, Maurice A Curtis, Richard LM Faul, Christopher A Ross, Andrea Caricasole, Hilal Lashuel. TBK1 1 1 thyylates mutant Huntingtin and suppresses its aggregation and toxicity in Huntington's disease models. The EMBO Journal, 2020; DOI: 10.15252/embj.2020104671.