Regulatory role of calpain in neuronal death

Cheng, Siying; Wang, Shu-chao; Lei, Ming; Wang, Zhen; Xiong, Kun

doi:10.4103/1673-5374.228762

Cited by 74 publications

(29 citation statements)

References 101 publications

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“…Intracellular Ca 2+ overload plays a major role in the development of cell injury (Cross et al, 2010 ). Activation of the Ca 2+ -dependent protease calpain is believed to be one mechanism by which increased [Ca 2+ ] r can cause damage (Hosfield et al, 1999 ; Cheng et al, 2018 ). Compared to young hippocampal neurons, calpain activity was significantly elevated in both middle-age (43%) and aged (113%) neurons ( Figure 3A ).…”

Section: Resultsmentioning

confidence: 99%

Memory and Learning Deficits Are Associated With Ca2+ Dyshomeostasis in Normal Aging

Uryash

Flores

Adams

et al. 2020

Front. Aging Neurosci.

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Neuronal intracellular Ca 2+ homeostasis is critical to the normal physiological functions of neurons and neuronal Ca 2+ dyshomeostasis has been associated with the age-related decline of cognitive functions. Accumulated evidence indicates that the underlying mechanism for this is that abnormal intracellular Ca 2+ levels stimulate the dysregulation of intracellular signaling, which subsequently induces neuronal cell death. We examined intracellular Ca 2+ homeostasis in cortical (in vivo) and hippocampal (in vitro) neurons from young (3-months), middle-age (12-months), and aged (24-months) wild type C57BL6J mice. We found a progressive age-related elevation of intracellular resting calcium ([Ca 2+ ] r) in cortical (in vivo) and hippocampal (in vitro) neurons associated with increased hippocampal neuronal calpain activity and reduced cell viability. In vitro, removal of extracellular Ca 2+ or treatment with SAR7334 or dantrolene reduced [Ca 2+ ] r in all age groups and dantrolene treatment lowered calpain activity and increased cell viability. In vivo, both middle-aged and aged mice showed cognitive deficits compared to young mice, which improved after dantrolene treatment. These findings support the hypothesis that intracellular Ca 2+ dyshomeostasis is a major mechanism underlying the cognitive deficits seen in both normal aging and degenerative neurologic diseases.

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Section: Resultsmentioning

confidence: 99%

Memory and Learning Deficits Are Associated With Ca2+ Dyshomeostasis in Normal Aging

Uryash

Flores

Adams

et al. 2020

Front. Aging Neurosci.

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“…It has been hypothesised that elevated cGMP leads to increased Ca 2+ influx via cyclic nucleotide-gated (CNG) channels [ 61 , 62 ], and that high intracellular Ca 2+ can trigger ER stress responses [ 63 ]. Further, raised intracellular Ca 2+ can activate a group of proteolytic enzymes known as Calpains, triggering apoptosis via the activation of AIF and caspase-7 [ 64 ] ( Figure 1 B,C). Whilst there is no direct evidence that raised intracellular calcium leads to ER stress-mediated photoreceptor death in RP, a body of work on phosphodiesterase subunit b (PDE6b)-mediated RP is suggestive of this.…”

Section: Pathways Leading To the Death Of Rod Photoreceptors In Rpmentioning

confidence: 99%

Mechanisms of Photoreceptor Death in Retinitis Pigmentosa

Newton

Megaw

2020

Genes

146

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Retinitis pigmentosa (RP) is the most common cause of inherited blindness and is characterised by the progressive loss of retinal photoreceptors. However, RP is a highly heterogeneous disease and, while much progress has been made in developing gene replacement and gene editing treatments for RP, it is also necessary to develop treatments that are applicable to all causative mutations. Further understanding of the mechanisms leading to photoreceptor death is essential for the development of these treatments. Recent work has therefore focused on the role of apoptotic and non-apoptotic cell death pathways in RP and the various mechanisms that trigger these pathways in degenerating photoreceptors. In particular, several recent studies have begun to elucidate the role of microglia and innate immune response in the progression of RP. Here, we discuss some of the recent progress in understanding mechanisms of rod and cone photoreceptor death in RP and summarise recent clinical trials targeting these pathways.

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“…Unlike apoptosis, parthanatos neither forms apoptotic bodies nor causes small DNA fragments. Unlike necrosis and authophagy, it does not trigger cell swelling or lysosomal degradation (9). As it cannot be rescued by a pan-caspase inhibitor (z-VAD-fmk), it is also a type of caspase-independent apoptosis (10).…”

Section: Introductionmentioning

confidence: 99%

Hydrogen‑rich medium alleviates high glucose‑induced oxidative stress and parthanatos in rat Schwann cells in�vitro

Jiao

et al. 2018

Mol Med Report

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Diabetic peripheral neuropathy (DPN) is considered to be the most common cause of microvascular diabetic complications, for which no effective therapies currently exist. Previous studies have identified that oxidative stress is the common pathway in all possible hypotheses for the induction of DPN, and poly(ADP-ribose) (PAR) polymerase-1 (PARP-1)-dependent cell death (parthanatos) is key in the pathogenic mechanisms of neurodegenerative disease. The aim of the present study was to investigate the protective effects and corresponding mechanisms of hydrogen-rich medium (HM) on high glucose (HG)-induced oxidative stress and parthanatos in primary rat Schwann cells (RSCs) in vitro. The RSCs were divided into groups and treated for 48 h. Cell counting kit-8 and lactate dehydrogenase assays were used to detect cell viability and cytotoxicity, respectively; intracellular OH− levels were measured using a DCFH-DA assay; concentrations of peroxynitrite (ONOO−) and 8-hydroxy deoxyguanosine (8-OHdG) were evaluated with an enzyme-linked immunosorbent assay; relative expression levels of parthanatos-related proteins [PAR, nucleus apoptosis-inducing factor (AIF) and total AIF] were analyzed using western blot analysis, and immunofluorescence was used to determine the nuclear translocation of AIF. After 48 h, HG was shown to induce severe oxidative stress and promote marked levels of parthanatos in the RSCs. Treatment with HM inhibited HG-induced oxidative stress by reducing the production of OH− and ONOO− and suppressed parthanatos by downregulating the levels of 8-OHdG, the expression of PAR and the nuclear translocation of AIF. HM improved cell viability and inhibited cytotoxicity under the HG condition. These results indicate that HM effectively reduces HG-induced oxidative stress in RSCs and protects them against parthanatos. Therefore, HM may be a novel treatment for DPN.

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Regulatory role of calpain in neuronal death

Cited by 74 publications

References 101 publications

Memory and Learning Deficits Are Associated With Ca2+ Dyshomeostasis in Normal Aging

Memory and Learning Deficits Are Associated With Ca2+ Dyshomeostasis in Normal Aging

Mechanisms of Photoreceptor Death in Retinitis Pigmentosa

Hydrogen‑rich medium alleviates high glucose‑induced oxidative stress and parthanatos in rat Schwann cells in�vitro

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