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Chapter 5 Autophagic Clearance of Aggregate‐Prone Proteins Associated with Neurodegeneration
Abstract
Autophagy has emerged as a field of rapidly growing interest with implications in several disease conditions, such as cancer, infectious diseases, and neurodegenerative diseases. Autophagy is a major degradation pathway for aggregate-prone, intracytosolic proteins causing neurodegenerative disorders, such as Huntington's disease and forms of Parkinson's disease. Up-regulating autophagy may be a tractable therapeutic intervention for clearing these disease-causing proteins. The identification of autophagy-enhancing compounds would be beneficial not only in neurodegenerative diseases but also in other conditions where up-regulating autophagy may act as a protective pathway. Furthermore, small molecule modulators of autophagy may also be useful in dissecting pathways governing mammalian autophagy. In this chapter, we highlight assays that can be used for the identification of autophagy regulators, such as measuring the clearance of mutant aggregate-prone proteins or of autophagic flux with bafilomycin A(1). Using these methods, we recently described several mTOR-independent autophagy-enhancing compounds that have protective effects in various models of Huntington's disease.
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“This approach, however, is only valid when the knockdown of LAMP2 is directed against the mRNA region specific for the LAMP2B spliced variant, as targeting the region common to the three variants would also inhibit chaperone-mediated autophagy (CMA), which may result in the compensatory upregulation of autophagy [135,309,310].”
From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [310]
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Metadata
- Authors
- Sarkar, S., Ravikumar, B., & Rubinsztein, D. C.
- Venue
- Methods in Enzymology
- Publisher
- Elsevier
- Published
- 2009
- Pages
- 83-110
- ISSN
- 0076-6879
- Cited by
- 79
- References
- 15
- Language
- en
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