The enzyme beta-secretase generates amyloid-beta peptides, the constituents of the damaging amyloid plaques in Alzheimer’s disease. In order to halt the disease, researchers are developing drugs aiming to block the enzyme. However, Bace1, as the enzyme is abbreviated, is full of surprises. Together with the growth factor Neuregulin-1, Bace1 is essential for the formation and maintenance of the function of muscle spindles, which ensure a constant muscle tone and protect muscles from overstretching. As the developmental biologist Dr. Cyril Cheret from the research group of Professor Carmen Birchmeier at the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch demonstrated on mice, the muscle spindles do not form properly when Bace1 is lacking during development. Moreover, inhibition of Bace1 activity in adult suffices to severely impair muscle spindle function (EMBO Journal, doi:10.1038/emboj.2013.146)*.
The young researcher’s findings are of particular importance with regard to the development of Bace1 inhibitors for the treatment of Alzheimer’s disease. Cyril Cheret, Carmen Birchmeier and their colleagues are concerned that Bace1 inhibitors may even impair the function of muscle spindles in patients and may lead to difficulties in movement coordination.
In recent years, the research team in the laboratory of Carmen Birchmeier, in collaboration with Dr. Alistair Garratt (Institute of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin) and the group of Professor Christian Haass (Ludwig-Maximilians-Universität Munich) has deciphered various functions of Bace1. These studies demonstrated that inactivation of Bace1 could be a double-edged sword.
*Bace1 and Neuregulin-1 cooperate to control formation and maintenance of muscle spindles
Cyril Cheret1, Michael Willem2, Florence R Fricker3, Hagen Wende1, Annika Wulf-Goldenberg4, Sabina Tahirovic5, Klaus-Armin Nave6, Paul Saftig7, Christian Haass2,5,8, Alistair N Garratt9, David L Bennett3 and Carmen Birchmeier1,*
1Entwicklungsbiologie/Signaltransduktion, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany, 2Adolf-Butenandt-Institute - Biochemistry, Ludwig-Maximilians-University Munich, Munich, Germany, 3Wolfson Centre for Age-Related Diseases, King’s College London, London, UK, 4Experimental Pharmacology & Oncology Berlin-Buch GmbH, Berlin, Germany, 5German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany, 6Max Planck Institute of Experimental Medicine, Göttingen, Germany, 7Biochemical Institute, Christian-Albrechts University Kiel, Kiel, Germany, 8Munich Cluster for Systems Neurology (SyNergy), Munich, Germany and 9Center for Anatomy, Institute of Cell Biology and Neurobiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
in the Helmholtz Association
Robert-Rössle-Straße 10; 13125 Berlin, Germany
Phone: +49 (0) 30 94 06 - 38 96; Fax: +49 (0) 30 94 06 - 38 33