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Cathepsin B - a lysosomal protease with potential of an important drug target in neurological diseases and cancer

Mon, 10/12/2015 - 14:56


Cathepsins are a family of lysosomal proteases (serine, aspartic and cysteine proteases) that acts in conjunction with lipases and nucleases to degrade biological macromolecules in the lysosomes (1). While most cathepsins are ubiquitously expressed to support normal lysosomal degradation, cathepsin B is unique for its role in various pathologies and malignancies (2). Cathepsin B is often overexpressed and alternatively spliced in cancer cells (2). Increased levels of cathepsin B lead to its secretion where it contributes to metastasis through the degradation of extracellular matrix proteins. Cathepsin B also has neuroprotective effects in neurological disorders such as Alzheimer’s and Huntington’s diseases. In these disorders, cathepsin B contributes to the degradation of toxic protein aggregates through autophagy (2).

The role of cathepsin B in diverse cellular processes makes it an important target and cathepsin B antibodies are great research tools in biomedical research. Researchers from Memorial Sloan Kettering Cancer Center investigated the role of cathepsin B in tumorigenesis and by using cathepsin B antibody for immunohistochemistry, they demonstrated an increased cathepsin B expression in pancreatic cancer tissues. Additionally, this study identified E-cadherin, a cell adhesion protein, as a substrate of cathepsin B (3). A separate study sought to identify additional secreted proteins that serve as biomarkers for pancreatic cancer. This study used a cathepsin B antibody for western blotting to validate and compare biomarker candidates (4). Cathepsin B degradation of extracellular matrix proteins can alter the tumor microenvironment and affect tumor growth. Shree et al. published research showing inhibition of cathepsin B can enhance chemotherapeutic response (5). This study used a cathepsin B antibody to show that an increased cathepsin B levels following drug treatment can protect cells from taxol-induced cell death (5). Inhibition of cathepsin B restored drug sensitivity and demonstrates the importance of integrated therapeutic strategies (5). A study by Halle et al. examined the role of cathepsin B in degradation of Alzheimer’s disease (6). Using a cathepsin B antibody for immunostaining, the study showed cathepsin B is released from the lysosome following amyloid- beta induced damage (6). Cathepsin B release then leads to the activation of the inflammasome and innate immune response (6).

Novus Biologicals offers Cathepsin B reagents for your research needs including:

PMIDs

  1. 22024571
  2. 23293836
  3. 16481467
  4. 16215274
  5. 22156207
  6. 18604209

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