Brie E Paddock

Publications (2)7.84 Total impact

• Article: Invertebrate Models of Alzheimer's Disease.

  Siddhita D Mhatre, Brie E Paddock, Aleister J Saunders, Daniel R Marenda
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  ABSTRACT: A majority of the genes linked to human disease belong to evolutionarily conserved pathways found in simpler organisms, such as Caenorhabditis elegans and Drosophila melanogaster. The genes and pathways of these simple organisms can be genetically and pharmacologically manipulated to better understand the function of their orthologs in vivo, and how these genes are involved in the pathogenesis of different diseases. Often these manipulations can be performed much more rapidly in flies and worms than in mammals, and can generate high quality in vivo data that is translatable to mammalian systems. Other qualities also make these organisms particularly well suited to the study of human disease. For example, developing in vivo disease models can help illuminate the basic mechanisms underlying disease, as in vitro studies do not always provide the natural physiological complexity associated with many diseases. Invertebrate models are relatively inexpensive, easy to work with, have short lifespans, and often have very well characterized and stereotypical development and behavior. This is particularly true for the two invertebrate model organisms that this review will focus on: Caenorhabditis elegans and Drosophila melanogaster. In this review, we will first describe an overview of modeling Alzheimer's disease in flies and worms, and will then highlight some of the more recent advances that these "simple" animals have contributed to our understanding of Alzheimer's disease in recent years.
  Journal of Alzheimer's disease: JAD 08/2012; · 3.74 Impact Factor
• Source

  Available from: Sara Ansaloni

  Article: Characterization of a Drosophila Alzheimer's disease model: pharmacological rescue of cognitive defects.

  Ranjita Chakraborty, Vidya Vepuri, Siddhita D Mhatre, Brie E Paddock, Sean Miller, Sarah J Michelson, Radha Delvadia, Arkit Desai, Marianna Vinokur, David J Melicharek, Suruchi Utreja, Preeti Khandelwal, Sara Ansaloni, Lee E Goldstein, Robert D Moir, Jeremy C Lee, Loni P Tabb, Aleister J Saunders, Daniel R Marenda
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  ABSTRACT: Transgenic models of Alzheimer's disease (AD) have made significant contributions to our understanding of AD pathogenesis, and are useful tools in the development of potential therapeutics. The fruit fly, Drosophila melanogaster, provides a genetically tractable, powerful system to study the biochemical, genetic, environmental, and behavioral aspects of complex human diseases, including AD. In an effort to model AD, we over-expressed human APP and BACE genes in the Drosophila central nervous system. Biochemical, neuroanatomical, and behavioral analyses indicate that these flies exhibit aspects of clinical AD neuropathology and symptomology. These include the generation of Aβ(40) and Aβ(42), the presence of amyloid aggregates, dramatic neuroanatomical changes, defects in motor reflex behavior, and defects in memory. In addition, these flies exhibit external morphological abnormalities. Treatment with a γ-secretase inhibitor suppressed these phenotypes. Further, all of these phenotypes are present within the first few days of adult fly life. Taken together these data demonstrate that this transgenic AD model can serve as a powerful tool for the identification of AD therapeutic interventions.
  PLoS ONE 01/2011; 6(6):e20799. · 4.09 Impact Factor