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O1‐02‐06: The Alzheimer's beta‐secretase enzyme BACE1 is required for accurate axon guidance of olfactory sensory neurons and normal glomerulus formation in the olfactory bulb
Author(s) -
Rajapaksha Tharu,
Vassar Robert
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.213
Subject(s) - axon , olfactory bulb , amyloid precursor protein , olfactory marker protein , green fluorescent protein , neuroscience , biology , glomerulus , olfactory system , microbiology and biotechnology , bace1 as , alzheimer's disease , pathology , central nervous system , gene , endocrinology , biochemistry , medicine , disease , kidney
Background The β-secretase, β-site amyloid precursor protein cleaving enzyme 1 (BACE1), is a prime therapeutic target for lowering cerebral β-amyloid (Aβ) levels in Alzheimer's disease (AD). Clinical development of BACE1 inhibitors is being intensely pursued. However, little is known about the physiological functions of BACE1, and the possibility exists that BACE1 inhibition may cause mechanism-based side effects. Indeed, BACE1-/- mice exhibit a complex neurological phenotype. Interestingly, BACE1 co-localizes with presynaptic neuronal markers, indicating a role in axons and/or terminals. Moreover, recent studies suggest axon guidance molecules are potential BACE1 substrates. Here, we used a genetic approach to investigate the function of BACE1 in axon guidance of olfactory sensory neurons (OSNs), a well-studied model of axon targeting in vivo.