Calcium‐activated Proteolysis of Intermediate Filaments<sup>a</sup>

Schlaepfer, William W.; Zimmerman, Un‐Jin P.

doi:10.1111/j.1749-6632.1985.tb50435.x

Cited by 36 publications

(21 citation statements)

References 30 publications

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“…Ca 2+ elevation is the earliest sign of axonal dysfunction, potentially leading to neuronal damage (Nitsch et al, 2004;McKinney et al, 1999), and involves the same pathways under a variety of pathophysiologic conditions, e.g., stroke, traumatic CNS injury or inflammatory CNS disease. A sustained influx of Ca 2+ is sufficient to induce Wallerian degeneration most likely by means of Ca 2+ -activated proteases, which causes cytoskeletal and neurofilamental degradation (Schlaepfer and Zimmerman, 1985). In line with these findings, in EAE, a therapeutic blockade of excitotoxic receptors has been proven to be effective (Pitt et al, 2000;Basso et al, 2008;Smith et al, 2000).…”

Section: Discussionmentioning

confidence: 92%

In Vivo Imaging of Partially Reversible Th17 Cell-Induced Neuronal Dysfunction in the Course of Encephalomyelitis

et al. 2010

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Neuronal damage in autoimmune neuroinflammation is the correlate for long-term disability in multiple sclerosis (MS) patients. Here, we investigated the role of immune cells in neuronal damage processes in animal models of MS by monitoring experimental autoimmune encephalomyelitis (EAE) by using twophoton microscopy of living anaesthetized mice. In the brainstem, we detected sustained interaction between immune and neuronal cells, particularly during disease peak. Direct interaction of myelin oligodendrocyte glycoprotein (MOG)-specific Th17 and neuronal cells in demyelinating lesions was associated with extensive axonal damage. By combining confocal, electron, and intravital microscopy, we showed that these contacts remarkably resembled immune synapses or kinapses, albeit with the absence of potential T cell receptor engagement. Th17 cells induced severe, localized, and partially reversible fluctuation in neuronal intracellular Ca 2+ concentration as an early sign of neuronal damage. These results highlight the central role of the Th17 cell effector phenotype for neuronal dysfunction in chronic neuroinflammation.

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Section: Discussionmentioning

confidence: 92%

In Vivo Imaging of Partially Reversible Th17 Cell-Induced Neuronal Dysfunction in the Course of Encephalomyelitis

et al. 2010

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“…In this case, it is evident that the increased neuronal calcium over the limit of 1 µM appears only at the inflammation sites. Electrophysiological measurements in primary neuronal cultures identified a sustained 1 µM intracellular calcium concentration to lead to cell death [32]. …”

Section: Resultsmentioning

confidence: 99%

Intravital FRET: Probing Cellular and Tissue Function in Vivo

Radbruch

Bremer

Mothes

et al. 2015

IJMS

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The development of intravital Förster Resonance Energy Transfer (FRET) is required to probe cellular and tissue function in the natural context: the living organism. Only in this way can biomedicine truly comprehend pathogenesis and develop effective therapeutic strategies. Here we demonstrate and discuss the advantages and pitfalls of two strategies to quantify FRET in vivo—ratiometrically and time-resolved by fluorescence lifetime imaging—and show their concrete application in the context of neuroinflammation in adult mice.

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“…Indeed, several lines of evidence indicate that cytoskeletal disassembly (Schlaepfer and Bunge, 1973;Meiri er al., 1983;Xie and Barret, 1991) and slow axonal transport impairment (Oblinger and Lasek, 1988;McKerracher et al, 1990) occur following nerve injury. In addition, the cytoskeletal disruption which follows axotomy has been attributed to increased calcium influx (Schlaepfer and Bunge, 1973;Schlaepfer and Zimmerman, 1985; Xie and Barret, 1991). Taken together, these data indicate that nerve injury induces an increase in intracellular calcium concentration which triggers a series of functional modifications of lesioned neurons, leading either to cell death or to partial recovery (Laiwand et al, 1988).…”

Section: Introductionmentioning

confidence: 93%

Exposure to Kainic Acid Mimics the Effects of Axotomy in Cerebellar Purkinje Cells of the Adult Rat

Rossi

Borsello

Strata

1994

Eur J of Neuroscience

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We have investigated the long-term structural changes which affect Purkinje cells exposed to a single dose of kainic acid. Following intraparenchymal injection of the excitotoxin in the cerebellar cortex (1 microliter of a 1 mg/ml solution), Purkinje cells which survived within the lesioned area or close to its edges showed remarkable axonal abnormalities, involving the formation of torpedoes, hypertrophy of recurrent collaterals and atrophy of the corticofugal portion of the axon. In addition, their dendritic trees were often affected by conspicuous regressive alterations. The climbing fibres contacting these Purkinje cells were characterized by thick perisomatic plexuses, whereas their peridendritic branches were atrophic. The dendrites innervated by such atrophic olivary arbours were studded with huge numbers of newly formed spines. These alterations were already present a few days after kainic acid administration and persisted for the total period of observation of 6 months after the lesion. The remarkable similarity between the abnormalities of Purkinje cells exposed to kainic acid and those observed after axotomy indicates that in these two conditions common mechanisms determine analogous long-lasting modifications in the affected neurons. It is proposed that kainic acid-induced intracellular calcium overload disrupts cytoskeletal components and impairs axonal transport, thus depriving the affected Purkinje cells of retrograde trophic influences from their target neurons. As a consequence the affected neurons undergo long-lasting regressive modifications and compensatory remodelling phenomena.

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Calcium‐activated Proteolysis of Intermediate Filaments^a

Cited by 36 publications

References 30 publications

In Vivo Imaging of Partially Reversible Th17 Cell-Induced Neuronal Dysfunction in the Course of Encephalomyelitis

In Vivo Imaging of Partially Reversible Th17 Cell-Induced Neuronal Dysfunction in the Course of Encephalomyelitis

Intravital FRET: Probing Cellular and Tissue Function in Vivo

Exposure to Kainic Acid Mimics the Effects of Axotomy in Cerebellar Purkinje Cells of the Adult Rat

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Calcium‐activated Proteolysis of Intermediate Filamentsa

Cited by 36 publications

References 30 publications

In Vivo Imaging of Partially Reversible Th17 Cell-Induced Neuronal Dysfunction in the Course of Encephalomyelitis

In Vivo Imaging of Partially Reversible Th17 Cell-Induced Neuronal Dysfunction in the Course of Encephalomyelitis

Intravital FRET: Probing Cellular and Tissue Function in Vivo

Exposure to Kainic Acid Mimics the Effects of Axotomy in Cerebellar Purkinje Cells of the Adult Rat

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Product

Resources

About

Calcium‐activated Proteolysis of Intermediate Filaments^a