NDLI: Induction of heat shock proteins in cerebral cortical cultures by celastrol

Content Provider	PubMed Central
Author	Chow, Ari M. Tang, Derek W. F. Hanif, Asad Brown, Ian R.
Abstract	Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis (ALS) are ‘protein misfolding disorders’ of the mature nervous system that are characterized by the accumulation of protein aggregates and selective cell loss. Different brain regions are impacted, with Alzheimer’s affecting cells in the cerebral cortex, Parkinson’s targeting dopaminergic cells in the substantia nigra and ALS causing degeneration of cells in the spinal cord. These diseases differ widely in frequency in the human population. Alzheimer’s is more frequent than Parkinson’s and ALS. Heat shock proteins (Hsps) are ‘protein repair agents’ that provide a line of defense against misfolded, aggregation-prone proteins. We have suggested that differing levels of constitutively expressed Hsps (Hsc70 and Hsp27) in neural cell populations confer a variable buffering capacity against ‘protein misfolding disorders’ that correlates with the relative frequencies of these neurodegenerative diseases. The high relative frequency of Alzheimer’s may due to low levels of Hsc70 and Hsp27 in affected cell populations that results in a reduced defense capacity against protein misfolding. Here, we demonstrate that celastrol, but not classical heat shock treatment, is effective in inducing a set of neuroprotective Hsps in cultures derived from cerebral cortices, including Hsp70, Hsp27 and Hsp32. This set of Hsps is induced by celastrol at ‘days in vitro’ (DIV) 13 when cultured cortical cells reached maturity. The inducibility of a set of neuroprotective Hsps in mature cortical cultures at DIV13 suggests that celastrol is a potential agent to counter Alzheimer’s disease, a neurodegenerative ‘protein misfolding disorder’ of the adult brain that targets cells in the cerebral cortex.
Related Links	http://dx.doi.org/10.1007/s12192-012-0364-0
Ending Page	160
Page Count	6
Starting Page	155
File Format	PDF
ISSN	13558145
e-ISSN	14661268
Journal	Cell Stress & Chaperones
Issue Number	2
Volume Number	18
Language	English
Publisher	Springer Netherlands
Publisher Date	2013-03-01
Access Restriction	Open
Rights Holder	Springer Netherlands
Subject Keyword	Cell Biology Biochemistry Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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