Abstract
Over the past decades, the paradigm that lysosomal enzymes participate only in non-specific protein degradation during cell death has changed. Studies conducted both in cell cultures and in animals defined the role of these enzymes that includes cathepsin D (CD). Knockout mice revealed the role of CD in postnatal tissue homeostasis and remodeling. Mutations that abolish the CD enzymatic activity have been implicated in neural ceroid lipofuscinosis. Recent studies suggested a differential role of CD in regulation of apoptosis. The zymogen of CD, procathepsin D (pCD), is secreted by various cancer cells. Extensive studies showed that it acts as a mitogen on both cancer and stromal cells by stimulating their invasive and metastatic properties. Additional studies suggested that procathepsin D/CD is an independent prognostic factor in various cancers, leading to the investigations of pCD/CD as a potential target for designing anti-cancer therapy. In this review, we described the various forms of CD and their implications in numerous physiological as well as pathological conditions.
Keywords: Alzheimer's disease, apoptosis, cancer, cathepsin D, knockout mice, procathepsin D
Endocrine, Metabolic & Immune Disorders - Drug Targets
Title: Pleiotropic Effects of Cathepsin D
Volume: 9 Issue: 4
Author(s): Aruna Vashishta, Sujata Saraswat Ohri and Vaclav Vetvicka
Affiliation:
Keywords: Alzheimer's disease, apoptosis, cancer, cathepsin D, knockout mice, procathepsin D
Abstract: Over the past decades, the paradigm that lysosomal enzymes participate only in non-specific protein degradation during cell death has changed. Studies conducted both in cell cultures and in animals defined the role of these enzymes that includes cathepsin D (CD). Knockout mice revealed the role of CD in postnatal tissue homeostasis and remodeling. Mutations that abolish the CD enzymatic activity have been implicated in neural ceroid lipofuscinosis. Recent studies suggested a differential role of CD in regulation of apoptosis. The zymogen of CD, procathepsin D (pCD), is secreted by various cancer cells. Extensive studies showed that it acts as a mitogen on both cancer and stromal cells by stimulating their invasive and metastatic properties. Additional studies suggested that procathepsin D/CD is an independent prognostic factor in various cancers, leading to the investigations of pCD/CD as a potential target for designing anti-cancer therapy. In this review, we described the various forms of CD and their implications in numerous physiological as well as pathological conditions.
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Cite this article as:
Vashishta Aruna, Ohri Saraswat Sujata and Vetvicka Vaclav, Pleiotropic Effects of Cathepsin D, Endocrine, Metabolic & Immune Disorders - Drug Targets 2009; 9 (4) . https://dx.doi.org/10.2174/187153009789839174
DOI https://dx.doi.org/10.2174/187153009789839174 |
Print ISSN 1871-5303 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3873 |
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