The β-Secretase Enzyme BACE in Health and Alzheimer's Disease: Regulation, Cell Biology, Function, and Therapeutic Potential

Journal of Neuroscience - Tập 29 Số 41 - Trang 12787-12794 - 2009
Robert Vassar1, Dora M. Kovacs2, Riqiang Yan3, Philip C. Wong4
1Department of Cell and Molecular Biology, Northwestern University, Chicago, Illinois 60611
2MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Department of Neurology, Harvard Medical School, Charlestown, Massachusetts 02129,
3Department of Neuroscience, Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio 44195, and
4Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231

Tóm tắt

The β-amyloid (Aβ) peptide is the major constituent of amyloid plaques in Alzheimer's disease (AD) brain and is likely to play a central role in the pathogenesis of this devastating neurodegenerative disorder. The β-secretase, β-site amyloid precursor protein cleaving enzyme (BACE1; also called Asp2, memapsin 2), is the enzyme responsible for initiating Aβ generation. Thus, BACE is a prime drug target for the therapeutic inhibition of Aβ production in AD. Since its discovery 10 years ago, much has been learned about BACE. This review summarizes BACE properties, describes BACE translation dysregulation in AD, and discusses BACE physiological functions in sodium current, synaptic transmission, myelination, and schizophrenia. The therapeutic potential of BACE will also be considered. This is a summary of topics covered at a symposium held at the 39th annual meeting of the Society for Neuroscience and is not meant to be a comprehensive review of BACE.

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Journal of Neuroscience

Tập 29 Số 41

12787-12794

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