Abstract
Endolysosomal proteases such as cysteinyl and aspartyl cathepsins play diverse roles in inflammatory autoimmune diseases, cancers, and neurodegenerative diseases. Cysteinyl cathepsin B and aspartyl cathepsin D levels are markedly elevated in a variety of neurological disorders including Alzheimers disease (AD), a leading cause of dementia in the elderly. Studies have also shown an increased cathepsin activity in AD patients where senile plaques and neuronal loss are marked features of the disease. Senile plaques contain amyloid-beta (Aβ) peptide, which is produced by proteolytic cleavage of the amyloid precursor protein (APP) by the proteases. In this article, we present the current knowledge of cysteinyl and aspartyl cathepsins in cellular and molecular events that lead to formation of senile plaques in AD. This article also focused on the role of cathepsin inhibitors as disease-modifying treatment strategies that could halt, or even prevent, this devastating neurological disorder.
Keywords: Cathepsins, amyloid-beta (Aβ) peptide, immune responses, autophagy, neurodegeneration, apoptosis, Alzheimer's disease (AD), cathepsin inhibitors
CNS & Neurological Disorders - Drug Targets
Title: New Insights into the Roles of Endolysosomal Cathepsins in the Pathogenesis of Alzheimers Disease: Cathepsin Inhibitors as Potential Therapeutics
Volume: 7 Issue: 3
Author(s): Azizul Haque, Naren L. Banik and Swapan K. Ray
Affiliation:
Keywords: Cathepsins, amyloid-beta (Aβ) peptide, immune responses, autophagy, neurodegeneration, apoptosis, Alzheimer's disease (AD), cathepsin inhibitors
Abstract: Endolysosomal proteases such as cysteinyl and aspartyl cathepsins play diverse roles in inflammatory autoimmune diseases, cancers, and neurodegenerative diseases. Cysteinyl cathepsin B and aspartyl cathepsin D levels are markedly elevated in a variety of neurological disorders including Alzheimers disease (AD), a leading cause of dementia in the elderly. Studies have also shown an increased cathepsin activity in AD patients where senile plaques and neuronal loss are marked features of the disease. Senile plaques contain amyloid-beta (Aβ) peptide, which is produced by proteolytic cleavage of the amyloid precursor protein (APP) by the proteases. In this article, we present the current knowledge of cysteinyl and aspartyl cathepsins in cellular and molecular events that lead to formation of senile plaques in AD. This article also focused on the role of cathepsin inhibitors as disease-modifying treatment strategies that could halt, or even prevent, this devastating neurological disorder.
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Cite this article as:
Haque Azizul, Banik L. Naren and Ray K. Swapan, New Insights into the Roles of Endolysosomal Cathepsins in the Pathogenesis of Alzheimers Disease: Cathepsin Inhibitors as Potential Therapeutics, CNS & Neurological Disorders - Drug Targets 2008; 7 (3) . https://dx.doi.org/10.2174/187152708784936653
DOI https://dx.doi.org/10.2174/187152708784936653 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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