The unfolded protein response and the role of protein disulphide isomerase in neurodegeneration.
The maintenance and regulation of proteostasis is a critical function for post-mitotic neurons and dysregulation of proteostasis is increasingly implicated in neurodegenerative diseases. Despite having different clinical manifestations, these disorders share similar pathology; an accumulation of mis...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fcell.2015.00080/full |
| _version_ | 1818058823784464384 |
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| author | Emma ePerri Colleen eThomas Sonam eParakh Damian eSpencer Julie eAtkin Julie eAtkin |
| author_facet | Emma ePerri Colleen eThomas Sonam eParakh Damian eSpencer Julie eAtkin Julie eAtkin |
| author_sort | Emma ePerri |
| collection | DOAJ |
| description | The maintenance and regulation of proteostasis is a critical function for post-mitotic neurons and dysregulation of proteostasis is increasingly implicated in neurodegenerative diseases. Despite having different clinical manifestations, these disorders share similar pathology; an accumulation of misfolded proteins in neurons and subsequent disruption to cellular proteostasis. The endoplasmic reticulum (ER) is an important component of proteostasis, and when the accumulation of misfolded proteins occurs within the ER, this disturbs ER homeostasis, giving rise to ER stress. This triggers the unfolded protein response (UPR), distinct signalling pathways that whilst initially protective, are pro-apoptotic if ER stress is prolonged. ER stress is increasingly implicated in neurodegenerative diseases, and emerging evidence highlights the complexity of the UPR in these disorders, with both protective and detrimental components being described. Protein Disulphide Isomerase (PDI) is an ER chaperone induced during ER stress that is responsible for the formation of disulphide bonds in proteins. Whilst initially considered to be protective, recent studies have revealed unconventional roles for PDI in neurodegenerative diseases, distinct from its normal function in the UPR and the ER, although these mechanisms remain poorly defined. However specific aspects of PDI function may offer the potential to be exploited therapeutically in the future. This review will focus on the evidence linking ER stress and the UPR to neurodegenerative diseases, with particular emphasis on the emerging functions ascribed to PDI in these conditions. |
| first_indexed | 2024-12-10T13:06:45Z |
| format | Article |
| id | doaj.art-090f411bf5ab4122a81a6088152b78d6 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-10T13:06:45Z |
| publishDate | 2016-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-090f411bf5ab4122a81a6088152b78d62022-12-22T01:47:50ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2016-01-01310.3389/fcell.2015.00080176116The unfolded protein response and the role of protein disulphide isomerase in neurodegeneration.Emma ePerri0Colleen eThomas1Sonam eParakh2Damian eSpencer3Julie eAtkin4Julie eAtkin5La Trobe Institute for Molecular ScienceDepartment of Physiology, Anatomy and MicrobiologyMacquarie University, SydneyLa Trobe Institute for Molecular ScienceMacquarie University, SydneyLa Trobe Institute for Molecular ScienceThe maintenance and regulation of proteostasis is a critical function for post-mitotic neurons and dysregulation of proteostasis is increasingly implicated in neurodegenerative diseases. Despite having different clinical manifestations, these disorders share similar pathology; an accumulation of misfolded proteins in neurons and subsequent disruption to cellular proteostasis. The endoplasmic reticulum (ER) is an important component of proteostasis, and when the accumulation of misfolded proteins occurs within the ER, this disturbs ER homeostasis, giving rise to ER stress. This triggers the unfolded protein response (UPR), distinct signalling pathways that whilst initially protective, are pro-apoptotic if ER stress is prolonged. ER stress is increasingly implicated in neurodegenerative diseases, and emerging evidence highlights the complexity of the UPR in these disorders, with both protective and detrimental components being described. Protein Disulphide Isomerase (PDI) is an ER chaperone induced during ER stress that is responsible for the formation of disulphide bonds in proteins. Whilst initially considered to be protective, recent studies have revealed unconventional roles for PDI in neurodegenerative diseases, distinct from its normal function in the UPR and the ER, although these mechanisms remain poorly defined. However specific aspects of PDI function may offer the potential to be exploited therapeutically in the future. This review will focus on the evidence linking ER stress and the UPR to neurodegenerative diseases, with particular emphasis on the emerging functions ascribed to PDI in these conditions.http://journal.frontiersin.org/Journal/10.3389/fcell.2015.00080/fullneurodegenerationAmyotrophic lateral sclerosis (ALS)Alzheimer’s disease (AD)unfolded protein response (UPR)Parkinson’s disease (PD)Protein disulphide isomerase (PDI) |
| spellingShingle | Emma ePerri Colleen eThomas Sonam eParakh Damian eSpencer Julie eAtkin Julie eAtkin The unfolded protein response and the role of protein disulphide isomerase in neurodegeneration. Frontiers in Cell and Developmental Biology neurodegeneration Amyotrophic lateral sclerosis (ALS) Alzheimer’s disease (AD) unfolded protein response (UPR) Parkinson’s disease (PD) Protein disulphide isomerase (PDI) |
| title | The unfolded protein response and the role of protein disulphide isomerase in neurodegeneration. |
| title_full | The unfolded protein response and the role of protein disulphide isomerase in neurodegeneration. |
| title_fullStr | The unfolded protein response and the role of protein disulphide isomerase in neurodegeneration. |
| title_full_unstemmed | The unfolded protein response and the role of protein disulphide isomerase in neurodegeneration. |
| title_short | The unfolded protein response and the role of protein disulphide isomerase in neurodegeneration. |
| title_sort | unfolded protein response and the role of protein disulphide isomerase in neurodegeneration |
| topic | neurodegeneration Amyotrophic lateral sclerosis (ALS) Alzheimer’s disease (AD) unfolded protein response (UPR) Parkinson’s disease (PD) Protein disulphide isomerase (PDI) |
| url | http://journal.frontiersin.org/Journal/10.3389/fcell.2015.00080/full |
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