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Secreted Chaperones in Neurodegeneration
Kriti Chaplot1, Timothy S Jarvela1, Iris Lindberg1
1Department of Anatomy and Neurobiology, University of Maryland School of Medicine, University of Maryland, Baltimore, Baltimore, MD, United States.
Frontiers in Aging Neuroscience
|November 16, 2020
Summary
Secreted chaperones are crucial for maintaining protein homeostasis and preventing neurodegeneration. This review highlights key extracellular proteins like clusterin and progranulin that show therapeutic potential for diseases such as Alzheimer's and Parkinson's.
Area of Science:
- Neuroscience
- Molecular Biology
- Cellular Biology
Background:
- Protein homeostasis (proteostasis) is vital for cellular function, involving protein synthesis, folding, processing, and degradation.
- Disruptions in proteostasis lead to protein misfolding and aggregation, implicated in neurodegenerative diseases.
- While cytoplasmic chaperones are well-studied, extracellular chaperones secreted by brain cells are increasingly recognized for their role in neuronal proteostasis.
Purpose of the Study:
- To review the literature on secreted chaperones involved in neurodegenerative diseases.
- To identify common mechanisms and differences among these extracellular chaperones.
- To highlight their potential as biomarkers and therapeutic targets.
Main Methods:
- Literature review focusing on secreted chaperones including clusterin, progranulin, BRICHOS domain-containing proteins, 7B2/proSAAS, and small heat shock proteins (sHsps).
- Analysis of studies on their identification in protein aggregates, genetic associations, therapeutic efficacy in disease models, and secretion mechanisms.
- Synthesis of findings to compare and contrast the roles and mechanisms of different extracellular chaperones.
Main Results:
- Clusterin is found in protein aggregates and elevated CSF levels suggest biomarker and therapeutic potential.
- Progranulin, a genetic risk factor for frontotemporal lobar degeneration, shows promise in reducing neurodegenerative phenotypes in mouse models.
- BRICHOS proteins exhibit potent anti-amyloidogenic activity, and sHsps contribute to extracellular proteostasis and neuroprotection.
Conclusions:
- Extracellular chaperones play significant roles in neuronal proteostasis and neuroprotection.
- Specific secreted chaperones like clusterin and progranulin offer potential as therapeutic agents for neurodegenerative diseases.
- Further research into the mechanisms and therapeutic applications of these extracellular proteins is warranted.
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