naa a22 4500 510746489 CHVBK 20180411083048.0 cr unu---uuuuu 180411e20130301xx s 000 0 eng 10.1007/s12192-012-0364-0 doi (NATIONALLICENCE)springer-10.1007/s12192-012-0364-0 Induction of heat shock proteins in cerebral cortical cultures by celastrol [Elektronische Daten] [Ari Chow, Derek Tang, Asad Hanif, Ian Brown] 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. Cell Stress Society International, 2012 Hsp70 nationallicence Hsp32 nationallicence Hsp27 nationallicence Alzheimer's disease nationallicence Celastrol nationallicence ALS : Amyotrophic lateral sclerosis nationallicence DIV : Days in vitro nationallicence Chow Ari Centre for the Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, M1C 1A4, Toronto, ON, Canada aut Tang Derek Centre for the Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, M1C 1A4, Toronto, ON, Canada aut Hanif Asad Centre for the Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, M1C 1A4, Toronto, ON, Canada aut Brown Ian Centre for the Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, M1C 1A4, Toronto, ON, Canada aut Cell Stress and Chaperones Springer Netherlands 18/2(2013-03-01), 155-160 1355-8145 18:2<155 2013 18 12192 https://doi.org/10.1007/s12192-012-0364-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12192-012-0364-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chow Ari Centre for the Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, M1C 1A4, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Tang Derek Centre for the Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, M1C 1A4, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Hanif Asad Centre for the Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, M1C 1A4, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Brown Ian Centre for the Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, M1C 1A4, Toronto, ON, Canada aut NATIONALLICENCE 773 0- Cell Stress and Chaperones Springer Netherlands 18/2(2013-03-01), 155-160 1355-8145 18:2<155 2013 18 12192 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer