The heat shock response in neurons and astroglia and its role in neurodegenerative diseases
Abstract Protein inclusions are a predominant molecular pathology found in numerous neurodegenerative diseases, including amyotrophic lateral sclerosis and Huntington’s disease. Protein inclusions form in discrete areas of the brain characteristic to the type of neurodegenerative disease, and coinci...
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| Format: | Article |
| Language: | English |
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BMC
2017-09-01
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| Series: | Molecular Neurodegeneration |
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| Online Access: | http://link.springer.com/article/10.1186/s13024-017-0208-6 |
| _version_ | 1828771860884488192 |
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| author | Rebecca San Gil Lezanne Ooi Justin J. Yerbury Heath Ecroyd |
| author_facet | Rebecca San Gil Lezanne Ooi Justin J. Yerbury Heath Ecroyd |
| author_sort | Rebecca San Gil |
| collection | DOAJ |
| description | Abstract Protein inclusions are a predominant molecular pathology found in numerous neurodegenerative diseases, including amyotrophic lateral sclerosis and Huntington’s disease. Protein inclusions form in discrete areas of the brain characteristic to the type of neurodegenerative disease, and coincide with the death of neurons in that region (e.g. spinal cord motor neurons in amyotrophic lateral sclerosis). This suggests that the process of protein misfolding leading to inclusion formation is neurotoxic, and that cell-autonomous and non-cell autonomous mechanisms that maintain protein homeostasis (proteostasis) can, at times, be insufficient to prevent protein inclusion formation in the central nervous system. The heat shock response is a pro-survival pathway induced under conditions of cellular stress that acts to maintain proteostasis through the up-regulation of heat shock proteins, a superfamily of molecular chaperones, other co-chaperones and mitotic regulators. The kinetics and magnitude of the heat shock response varies in a stress- and cell-type dependent manner. It remains to be determined if and/or how the heat shock response is activated in the different cell-types that comprise the central nervous system (e.g. neurons and astroglia) in response to protein misfolding events that precede cellular dysfunctions in neurodegenerative diseases. This is particularly relevant considering emerging evidence demonstrating the non-cell autonomous nature of amyotrophic lateral sclerosis and Huntington’s disease (and other neurodegenerative diseases) and the destructive role of astroglia in disease progression. This review highlights the complexity of heat shock response activation and addresses whether neurons and glia sense and respond to protein misfolding and aggregation associated with neurodegenerative diseases, in particular Huntington’s disease and amyotrophic lateral sclerosis, by inducing a pro-survival heat shock response. |
| first_indexed | 2024-12-11T14:33:12Z |
| format | Article |
| id | doaj.art-3adad782d0ec4501958d8d56abb7d0f0 |
| institution | Directory Open Access Journal |
| issn | 1750-1326 |
| language | English |
| last_indexed | 2024-12-11T14:33:12Z |
| publishDate | 2017-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj.art-3adad782d0ec4501958d8d56abb7d0f02022-12-22T01:02:18ZengBMCMolecular Neurodegeneration1750-13262017-09-0112112010.1186/s13024-017-0208-6The heat shock response in neurons and astroglia and its role in neurodegenerative diseasesRebecca San Gil0Lezanne Ooi1Justin J. Yerbury2Heath Ecroyd3Illawarra Health and Medical Research Institute and School of Biological Sciences, University of WollongongIllawarra Health and Medical Research Institute and School of Biological Sciences, University of WollongongIllawarra Health and Medical Research Institute and School of Biological Sciences, University of WollongongIllawarra Health and Medical Research Institute and School of Biological Sciences, University of WollongongAbstract Protein inclusions are a predominant molecular pathology found in numerous neurodegenerative diseases, including amyotrophic lateral sclerosis and Huntington’s disease. Protein inclusions form in discrete areas of the brain characteristic to the type of neurodegenerative disease, and coincide with the death of neurons in that region (e.g. spinal cord motor neurons in amyotrophic lateral sclerosis). This suggests that the process of protein misfolding leading to inclusion formation is neurotoxic, and that cell-autonomous and non-cell autonomous mechanisms that maintain protein homeostasis (proteostasis) can, at times, be insufficient to prevent protein inclusion formation in the central nervous system. The heat shock response is a pro-survival pathway induced under conditions of cellular stress that acts to maintain proteostasis through the up-regulation of heat shock proteins, a superfamily of molecular chaperones, other co-chaperones and mitotic regulators. The kinetics and magnitude of the heat shock response varies in a stress- and cell-type dependent manner. It remains to be determined if and/or how the heat shock response is activated in the different cell-types that comprise the central nervous system (e.g. neurons and astroglia) in response to protein misfolding events that precede cellular dysfunctions in neurodegenerative diseases. This is particularly relevant considering emerging evidence demonstrating the non-cell autonomous nature of amyotrophic lateral sclerosis and Huntington’s disease (and other neurodegenerative diseases) and the destructive role of astroglia in disease progression. This review highlights the complexity of heat shock response activation and addresses whether neurons and glia sense and respond to protein misfolding and aggregation associated with neurodegenerative diseases, in particular Huntington’s disease and amyotrophic lateral sclerosis, by inducing a pro-survival heat shock response.http://link.springer.com/article/10.1186/s13024-017-0208-6NeurodegenerationAmyotrophic lateral sclerosisHuntington’s diseaseProteostasisHeat shock responseHeat shock factor 1 |
| spellingShingle | Rebecca San Gil Lezanne Ooi Justin J. Yerbury Heath Ecroyd The heat shock response in neurons and astroglia and its role in neurodegenerative diseases Molecular Neurodegeneration Neurodegeneration Amyotrophic lateral sclerosis Huntington’s disease Proteostasis Heat shock response Heat shock factor 1 |
| title | The heat shock response in neurons and astroglia and its role in neurodegenerative diseases |
| title_full | The heat shock response in neurons and astroglia and its role in neurodegenerative diseases |
| title_fullStr | The heat shock response in neurons and astroglia and its role in neurodegenerative diseases |
| title_full_unstemmed | The heat shock response in neurons and astroglia and its role in neurodegenerative diseases |
| title_short | The heat shock response in neurons and astroglia and its role in neurodegenerative diseases |
| title_sort | heat shock response in neurons and astroglia and its role in neurodegenerative diseases |
| topic | Neurodegeneration Amyotrophic lateral sclerosis Huntington’s disease Proteostasis Heat shock response Heat shock factor 1 |
| url | http://link.springer.com/article/10.1186/s13024-017-0208-6 |
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