Cathepsin B in neurodegeneration of Alzheimer's disease, traumatic brain injury, and related brain disorders.

Abstract

Investigations of Alzheimer's disease (AD), traumatic brain injury (TBI), and related brain disorders have provided extensive evidence for involvement of cathepsin B, a lysosomal cysteine protease, in mediating the behavioral deficits and neuropathology of these neurodegenerative diseases. This review integrates findings of cathepsin B regulation in clinical biomarker studies, animal model genetic and inhibitor evaluations, structural studies, and lysosomal cell biological mechanisms in AD, TBI, and related brain disorders. The results together indicate the role of cathepsin B in the behavioral deficits and neuropathology of these disorders. Lysosomal leakage occurs in AD and TBI, and related neurodegeneration, which leads to the hypothesis that cathepsin B is redistributed from the lysosome to the cytosol where it initiates cell death and inflammation processes associated with neurodegeneration. These results together implicate cathepsin B as a major contributor to these neuropathological changes and behavioral deficits. These findings support the investigation of cathepsin B as a potential drug target for therapeutic discovery and treatment of AD, TBI, and TBI-related brain disorders.

• Authors: Vivian Hook, Michael Yoon, Charles Mosier, Gen Ito, Sonia Podvin, Brian P Head, Robert Rissman, Anthony J O'Donoghue, Gregory Hook
• Journal: Biochimica et biophysica acta. Proteins and proteomics (Biochim Biophys Acta Proteins Proteom) Vol. 1868 Issue 8 Pg. 140428 (08 2020) ISSN: 1878-1454 [Electronic] Netherlands
• PMID: 32305689 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Neuroprotective Agents
• CTSB protein, human
• Cathepsin B

Topics

• Adult
• Alzheimer Disease (drug therapy, enzymology, genetics, pathology)
• Animals
• Brain (drug effects, enzymology, pathology)
• Brain Injuries, Traumatic (drug therapy, enzymology, genetics, pathology)
• Cathepsin B (antagonists & inhibitors, genetics, metabolism)
• Cell Death (drug effects, genetics)
• Child
• Cytosol (drug effects, enzymology)
• Disease Models, Animal
• Fetus
• Gene Expression Regulation
• Humans
• Infant
• Lysosomes (drug effects, enzymology)
• Molecular Targeted Therapy
• Neurocognitive Disorders (drug therapy, enzymology, genetics, pathology)
• Neurons (drug effects, enzymology, pathology)
• Neuroprotective Agents (therapeutic use)
• Signal Transduction