Trends in Neurosciences
Abstract
Calpains are evolutionally conserved and widely expressed cysteine proteases that act at neutral pH. Unlike all other proteases, calpains are activated by Ca2+.
Under physiological conditions, cytoplasmic Ca2+ levels are typically in the μM range, which is much lower than the mM Ca2+ levels required for calpain activation in in vitro assays. Accordingly, how calpain is activated under physiological conditions has been a critical and long-standing question in the field.
A critical player in the activation of calpain appears to be Ttm50. Ttm50, a subunit of the TIM23 complex involved in the transport of proteins across the mitochondrial inner membrane, anchors calpain to Golgi/endoplasmic reticulum Ca2+ stores, while simultaneously increases the calcium sensitivity of calpain by directly interacting with calpain via its C-terminal FCP1 domain.
Calpains are activated by calcium transients in neuronal remodeling during development and by calcium overload in Wallerian degeneration and neurodegenerative diseases.
Given that axon loss is often an early sign of neurodegeneration, its prevention by inhibiting calpain activity may lead to treatments for neurodegenerative diseases.
| 论文编号: | DOI:10.1016/j.tins.2021.07.003 |
| 论文题目: | The Calcium-Dependent Protease Calpain in Neuronal Remodeling and Neurodegeneration |
| 英文论文题目: | The Calcium-Dependent Protease Calpain in Neuronal Remodeling and Neurodegeneration |
| 第一作者: | Elsayed Metwally, Guoli Zhao, Yong Q. Zhang |
| 英文第一作者: | Elsayed Metwally, Guoli Zhao, Yong Q. Zhang |
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| 发表年度: | 2021-08-20 |
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| 摘要: | Calpains are evolutionally conserved and widely expressed cysteine proteases that act at neutral pH. Unlike all other proteases, calpains are activated by Ca2+. Under physiological conditions, cytoplasmic Ca2+ levels are typically in the μM range, which is much lower than the mM Ca2+ levels required for calpain activation in in vitro assays. Accordingly, how calpain is activated under physiological conditions has been a critical and long-standing question in the field. A critical player in the activation of calpain appears to be Ttm50. Ttm50, a subunit of the TIM23 complex involved in the transport of proteins across the mitochondrial inner membrane, anchors calpain to Golgi/endoplasmic reticulum Ca2+ stores, while simultaneously increases the calcium sensitivity of calpain by directly interacting with calpain via its C-terminal FCP1 domain. Calpains are activated by calcium transients in neuronal remodeling during development and by calcium overload in Wallerian degeneration and neurodegenerative diseases. Given that axon loss is often an early sign of neurodegeneration, its prevention by inhibiting calpain activity may lead to treatments for neurodegenerative diseases. |
| 英文摘要: | Calpains are evolutionally conserved and widely expressed cysteine proteases that act at neutral pH. Unlike all other proteases, calpains are activated by Ca2+. Under physiological conditions, cytoplasmic Ca2+ levels are typically in the μM range, which is much lower than the mM Ca2+ levels required for calpain activation in in vitro assays. Accordingly, how calpain is activated under physiological conditions has been a critical and long-standing question in the field. A critical player in the activation of calpain appears to be Ttm50. Ttm50, a subunit of the TIM23 complex involved in the transport of proteins across the mitochondrial inner membrane, anchors calpain to Golgi/endoplasmic reticulum Ca2+ stores, while simultaneously increases the calcium sensitivity of calpain by directly interacting with calpain via its C-terminal FCP1 domain. Calpains are activated by calcium transients in neuronal remodeling during development and by calcium overload in Wallerian degeneration and neurodegenerative diseases. Given that axon loss is often an early sign of neurodegeneration, its prevention by inhibiting calpain activity may lead to treatments for neurodegenerative diseases. |
| 刊物名称: | Trends in Neurosciences |
| 英文刊物名称: | Trends in Neurosciences |
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| 其它备注: | Elsayed Metwally, Guoli Zhao, Yong Q. Zhang. The Calcium-Dependent Protease Calpain in Neuronal Remodeling and Neurodegeneration. Trends in Neurosciences. DOI:10.1016/j.tins.2021.07.003 |
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