BACE: Therapeutic target and potential biomarker for Alzheimer's disease |
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| Authors: | Geneviève Evin Adel Barakat Colin L Masters |
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| Institution: | 1. VIB Center for the Biology of Disease, 3000 Leuven, Belgium;2. Center for Human Genetics, Universitaire Ziekenhuizen and LIND, KU Leuven, 3000 Leuven, Belgium;3. Neuroscience Department, Johnson & Johnson Pharmaceutical Research and Development, Janssen Pharmaceutica, Turnhoutseweg 30, 2340 Beerse, Belgium;4. German Center for Neurodegenerative Diseases (DZNE) and Munich Cluster for Systems Neurology (SyNergy), Feodor-Lynen-Straße 17, 81377 München, Germany;5. Neuroproteomics, Klinikum Rechts der Isar, and Institute for Advanced Study, Technische Universität München, 81675 München, Germany;6. Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK;1. Department of Psychiatry and Neurochemistry, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden;2. PerkinElmer Biosignal, Inc., 1744 William Street, Suite 600, Montreal, Que., Canada H3J 1R4;3. Department of Clinical Sciences, Lund University, Sweden;4. Neurology Clinic, Skåne University Hospital, Sweden;5. Memory Clinic, Skåne University Hospital, Sweden;6. Janssen Research and Development, Pharmaceutical Companies of Johnson & Johnson, Beerse, Belgium;7. UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK;1. Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA;2. Department of Cell and Molecular Biology, The Feinberg School of Medicine, Northwestern University, Chicago, IL, USA;1. Department of Neuroscience and Physiology, Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, University of Gothenburg, Mölndal, Sweden;2. Institute for Memory and Alzheimer''s Disease, Institute of Neurology, Pitié-Salpêtrière Hospital Group, Pierre and Marie Curie University, Paris, France;3. Department of Neurology, Washington University School of Medicine, St Louis, MO, USA;4. Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany;5. Department of Psychiatry, New York University School of Medicine, New York, NY, USA;6. Centre for Brain Health, New York University School of Medicine, New York, NY, USA;1. Center for Advanced Therapeutic Strategies for Brain Disorders, Roskamp Institute, Sarasota, FL 34203, USA;2. Center for Hormone Advanced Science and Education, Roskamp Institute, Sarasota, FL 34203, USA |
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| Abstract: | β-Site APP-cleaving enzyme (BACE) is a membrane-bound aspartyl protease involved in the production of Alzheimer's disease (AD) Aβ amyloid peptides. This enzyme is ubiquitously expressed, with highest levels in the brain and pancreas. Its cellular trafficking is tightly controlled as it recycles between endosomes and trans-Golgi network. BACE expression increases in response to aging and various stress stimuli. It is elevated in the brain cortex of AD sufferers, and increased levels of BACE in the cerebrospinal fluid of patients with mild cognitive impairment may provide an early biomarker of AD. BACE is considered as a rational drug target for AD therapy, and inhibitors are under development. Anomalies in the behaviour and biochemistry of BACE?/? mice have pointed to the role this enzyme plays in the processing of neuregulin and of voltage-gated sodium channel β-subunit. A full understanding of BACE biology in health and disease is needed to establish a safe AD therapy based on BACE inhibitors. |
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