German and UK-based researchers have recently affirmed that a protein, well established for the role it plays in the development of Alzheimer’s disease also, controls muscle development and leads to incapacitated movement in mice when the protein was treated with inhibitors or absent. Published in The EMBO Journal, the results suggest that medication, currently in development, that targets the beta-secretase-1 protein, may produce side effects that may impede movement.
Scientists have known for a while that the protein beta-secretase-1 (Bace 1 for short) is involved in the development of Alzheimer’s disease by generating Abeta peptides that form a plaque in the brain. Now, researchers have a better idea as to how Bace 1 works.
"Our results show that mice that lack Bace1 proteins or are treated with inhibitors of the enzyme have difficulties in coordination and walking and also show reduced muscle strength," commented Dr. Carmen Birchmeier, one of the authors of the paper. "In addition, we were able to show that the combined activities of Bace1 and another protein, neuregulin-1 or Nrg1, are needed to sustain the muscle spindles in mice and to maintain motor coordination."
Muscle spindles are found throughout the muscles of vertebrates and detect muscle strength and help the brain designate body position. The research team have utilized genetic analysis, various biochemical studies, Alzheimer's support group feedback, and interference with artificial inhibitors in order to better understand how Bace 1 functions in mice.
"If the signal strength of a specific form of neuregulin-1 known as IgNrg1 is gradually reduced, increasingly severe defects in the formation and maturation of muscle spindles are observed in mice. Furthermore, it appears that Bace1 is required for full IgNrg1 activity. The graded loss of IgNrg1 activity results in the animals having increasing difficulties with movement and coordination," stated Cyril Cheret, the report’s primary author.
Many parties are interested in completely stopping Bace1 because it seems like a simple solution to prevent and treat Alzheimer’s. "Our data indicate that one unwanted side effect of the long-term inhibition of Bace1 might be the disruption of muscle spindle formation and impairment of movement. This finding is relevant to scientists looking for ways to develop drugs that target the Bace1 protein and should be considered," says Dr. Birchmeier.