Articles by Kelley Bromley-Brits in JoVE
Morris Water Maze Test for Learning and Memory Deficits in Alzheimer's Disease Model Mice Kelley Bromley-Brits*1, Yu Deng*1, Weihong Song1 1Department of Psychiatry, Brain Research Center, University of British Columbia The Morris Water Maze is a behavioral task to test hippocampal-dependent learning and memory. It has been widely used in the study of neurobiology, neuropharmacology and neurocognitive disorders in rodent models.
Other articles by Kelley Bromley-Brits on PubMed
TMP21 Degradation is Mediated by the Ubiquitin-proteasome Pathway The European Journal of Neuroscience. Nov, 2008 | Pubmed ID: 19046380 The presenilin-associated complex regulates two independent intramembranous cleavage activities, i.e. gamma-secretase and epsilon-secretase activity. The gamma-secretase complex requires four critical components for its activity: presenilin 1, anterior pharynx-defective 1, nicastrin 1 and presenilin enhancer 2, all of which are degraded through the ubiquitin-proteasome pathway. Recently, TMP21, a type I transmembrane protein involved in endoplasmic reticulum/Golgi transport, was identified as a member of the presenilin complex. Knockdown of TMP21 selectively regulated pathogenic gamma-secretase activity, resulting in increased amyloid beta protein 40 and 42, without affecting the epsilon-cleavage of Notch. A further understanding of TMP21 degradation is required to examine the biological consequences of TMP21 protein level aberrations and their potential role in the pathogenesis of Alzheimer's disease and drug development. Here we show that human TMP21 has a short half-life of approximately 3 h. Treatment with proteasomal inhibitors can increase TMP21 protein levels in both a time- and dose-dependent manner, and both co-immunoprecipitation and immunofluorescent staining show that TMP21 is ubiquitinated. Inhibition of the lysosomal pathway failed to show a dose-dependent increase in TMP21 protein levels. Taken together, these results indicate that the degradation of TMP21, as with the other presenilin-associated gamma-secretase complex members, is mediated by the ubiquitin-proteasome pathway.
Transcriptional Regulation of TMP21 by NFAT Molecular Neurodegeneration. 2011 | Pubmed ID: 21375783 TMP21 is a member of the p24 cargo protein family, which is involved in protein transport between the Golgi apparatus and ER. Alzheimer's Disease (AD) is the most common neurodegenerative disorder leading to dementia and deposition of amyloid Î² protein (AÎ²) is the pathological feature of AD pathogenesis. Knockdown of TMP21 expression by siRNA causes a sharp increase in AÎ² production; however the underlying mechanism by which TMP21 regulates AÎ² generation is unknown, and human TMP21 gene expression regulation has not yet been studied.
Regulation of Î²-site APP-cleaving Enzyme 1 Gene Expression and Its Role in Alzheimer's Disease Journal of Neurochemistry. Jan, 2012 | Pubmed ID: 22122349 Alzheimer's disease (AD) is the most common neurodegenerative disorder leading to dementia. Neuritic plaques are the hallmark neuropathology in AD brains. Proteolytic processing of amyloid-Î² precursor protein at the Î² site by beta-site amyloid-Î² precursor protein-cleaving enzyme 1 (BACE1) is essential to generate AÎ², a central component of the neuritic plaques. BACE1 is increased in some sporadic AD brains, and dysregulation of BACE1 gene expression plays an important role in AD pathogenesis. This review will focus on the regulation of BACE1 gene expression at the transcriptional, post-transcriptional, translation initiation, translational and post-translational levels, and its role in AD pathogenesis. Further studies on BACE1 gene expression regulation will greatly contribute to our understanding of AD pathogenesis and reveal potential novel approaches for AD prevention and drug development.