Faculty
Anatomy and Cell Biology
Supervisor Name
Shawn Whitehead & Stephen Pasternak
Keywords
Ambroxol, Alzheimers Disease, Neurodegredation, Autophagy, Lysosome.
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Description
Alzheimer's Disease (AD) is a disease that sees pathological protein deposits in the form of Beta-Amyloid plaques and Tau neurofibrillary tangles that has been correlated with cognitive impairment and neurodegeneration. Microglia (MG) are considered the phagocytes of the brain, and evidence shows that under normal physiological conditions are responsible for the clearance and degradation of proteins in the brain. However, in AD and other neurodegenerative diseases, impaired MG functions are observed indicating issues with the autophagy/lysosomal system. Ambroxol is primarily used as a treatment for respiratory issues, however recent evidence supports its ability to stabilize glucocerebrosidase in Parkinson’s Disease (PD) patients, which results in increased clearance of alpha synuclein from the brain. This pilot study also demonstrated some cognitive improvements. Evidence has shown that Ambroxolupregulates TFEB in human fibroblasts, and controls cleavage enzymes that likely degrade beta-amyloid including lysosomal enzyme Cathepsin D (CatD) and LAMP1. Due to ambroxol’s ability to stabilize and seemingly increase clearance of proteins from the brain, further observations of ambroxol’s ability clear pathological proteins could also be of help in AD.
Acknowledgements
I would like to thank the Undergraduate Student Research Internship Scholarship, Dr. Shawn Whitehead, Dr. Steven Pasternak, Dr. Lin Zhao and the Schulich School of Medicine & Dentistry Faculty for their support.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Document Type
Video
Interrogating the effects of Ambroxol on lysosome enzymes in microglia
Alzheimer's Disease (AD) is a disease that sees pathological protein deposits in the form of Beta-Amyloid plaques and Tau neurofibrillary tangles that has been correlated with cognitive impairment and neurodegeneration. Microglia (MG) are considered the phagocytes of the brain, and evidence shows that under normal physiological conditions are responsible for the clearance and degradation of proteins in the brain. However, in AD and other neurodegenerative diseases, impaired MG functions are observed indicating issues with the autophagy/lysosomal system. Ambroxol is primarily used as a treatment for respiratory issues, however recent evidence supports its ability to stabilize glucocerebrosidase in Parkinson’s Disease (PD) patients, which results in increased clearance of alpha synuclein from the brain. This pilot study also demonstrated some cognitive improvements. Evidence has shown that Ambroxolupregulates TFEB in human fibroblasts, and controls cleavage enzymes that likely degrade beta-amyloid including lysosomal enzyme Cathepsin D (CatD) and LAMP1. Due to ambroxol’s ability to stabilize and seemingly increase clearance of proteins from the brain, further observations of ambroxol’s ability clear pathological proteins could also be of help in AD.