Quantifying immunohistochemical staining of phospho-eIF2α, heme oxygenase-2 and NADPH cytochrome P450 reductase in oligodendrocytes during experimental autoimmune encephalomyelitis

Chakrabarty, Anuradha; Fleming, Kandace; Marquis, Janet; Levine, Steven M.

doi:10.1016/j.jneumeth.2004.11.010

Cited by 7 publications

(6 citation statements)

References 48 publications

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“…Evidence of UPR activation, including increased CHOP and ATF4 mRNA, is found in demyelinating lesions of MS patients (Cunnea et al, 2011) and CHOP immunoreactivity is seen in multiple cell types, including oligodendrocytes, in active MS lesions (McMahon et al, 2012; Mháille et al, 2008). In agreement with the human MS findings, studies have detected evidence of UPR activation such as increased levels of phosphorylated eIF2α and CHOP protein in multiple cell types, including oligodendrocytes, within white matter lesions of EAE mice and rats (Chakrabarty et al, 2005, 2004; Lin et al, 2007; Ní Fhlathartaigh et al, 2013). Nevertheless, Chop gene ablation has been reported to have no effect on the EAE disease course (Deslauriers et al, 2011).…”

Section: Er Stress In Multiple Sclerosissupporting

confidence: 78%

Endoplasmic reticulum stress and the unfolded protein response in disorders of myelinating glia

Clayton

Popko

2016

Brain Research

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Myelin is vital to the proper function of the nervous system. Oligodendrocytes in the CNS and Schwann cells in the PNS are the glial cells responsible for generating the myelin sheath. Myelination requires the production of a vast amount of proteins and lipid-rich membrane, which puts a heavy load on the secretory pathway of myelinating glia and leaves them susceptible to endoplasmic reticulum (ER) stress. Cells respond to ER stress by activating the unfolded protein response (UPR). The UPR is initially protective but in situations of prolonged unresolved stress the UPR can lead to the apoptotic death of the stressed cell. There is strong evidence that ER stress and the UPR play a role in a number of disorders of myelin and myelinating glia, including multiple sclerosis, Pelizaeus-Merzbacher disease, Vanishing White Matter Disease, and Charcot-Marie-Tooth disease. In this review we discuss the role that ER stress and the UPR play in these disorders of myelin. In addition, we discuss the progress that has been made in our understanding of the effect genetic and pharmacological manipulation of the UPR has in mouse models of these disorders and the novel therapeutic potential of targeting the UPR that these studies support.

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Section: Er Stress In Multiple Sclerosissupporting

confidence: 78%

Endoplasmic reticulum stress and the unfolded protein response in disorders of myelinating glia

Clayton

Popko

2016

Brain Research

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“…Another recent report has shown elevated expression of CHOP, BIP and XBP-1 in multiple cell types within MS demyelinated lesions, including oligodendrocytes, astrocytes, T cells, and microglia 10. Moreover, elevated levels of p-eIF2α have been observed in oligodendrocytes and infiltrating T cells in the CNS during the course of EAE 70, 71.…”

Section: Er Stress Has Beneficial and Detrimental Effects On Oligodenmentioning

confidence: 99%

Endoplasmic reticulum stress in disorders of myelinating cells

2009

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Myelinating cells, oligodendrocytes in the CNS and Schwann cells in the PNS, produce an enormous amount of plasma membrane during the myelination process, making them particularly susceptible to disruptions to the secretory pathway. ER stress, initiated by the accumulation of unfolded or misfolded proteins, activates the unfolded protein response (UPR), which adapts cells to the stress. If this adaptive response is insufficient, the UPR activates an apoptotic program to eliminate the affected cells. Recent observations suggest that ER stress in myelinating cells plays an important role in the pathogenesis of various disorders of myelin, including Charcot-Marie-Tooth disease (CMT), Pelizaeus-Merzbacher disease (PMD), Vanishing White Matter Disease (VWMD), as well as in the most common disorder of myelin, multiples sclerosis (MS). A better understanding of ER stress in myelinating cells has laid the groundwork for the design of novel therapeutic strategies to promote myelinating cell survival in these disorders.

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“…Using biopsy specimens and post-mortem samples, immunohistochemistry analysis demonstrated increased expression of the UPR markers CHOP and BiP in oligodendrocytes, astrocytes, T cells and macrophages/microglia in MS lesions (Mháille et al, 2008 ; Cunnea et al, 2011 ; McMahon et al, 2012 ; Ní Fhlathartaigh et al, 2013 ). Moreover, elevated levels of several UPR markers, including p-PERK, p-eIF2α, BiP, and CHOP, have been demonstrated in oligodendrocytes, T cells, astrocytes, and macrophages/microglia during the course of EAE (Chakrabarty et al, 2004 , 2005 ; Lin et al, 2007 ; Deslauriers et al, 2011 ; Ní Fhlathartaigh et al, 2013 ; Meares et al, 2014 ).…”

Section: Activation Of the Upr In Ms And Eae Lesionsmentioning

confidence: 99%

The unfolded protein response in multiple sclerosis

Stone

Lin

2015

Front. Neurosci.

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The unfolded protein response (UPR) occurs in response to endoplasmic reticulum (ER) stress caused by the accumulation of unfolded or misfolded proteins in the ER. The UPR is comprised of three signaling pathways that promote cytoprotective functions to correct ER stress; however, if ER stress cannot be resolved the UPR results in apoptosis of affected cells. The UPR is an important feature of various human diseases, including multiple sclerosis (MS). Recent studies have shown several components of the UPR are upregulated in the multiple cell types in MS lesions, including oligodendrocytes, T cells, microglia/macrophages, and astrocytes. Data from animal model studies, particularly studies of experimental autoimmune encephalomyelitis (EAE) and the cuprizone model, imply an important role of the UPR activation in oligodendrocytes in the development of MS. In this review we will cover current literature on the UPR and the evidence for its role in the development of MS.

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Quantifying immunohistochemical staining of phospho-eIF2α, heme oxygenase-2 and NADPH cytochrome P450 reductase in oligodendrocytes during experimental autoimmune encephalomyelitis

Cited by 7 publications

References 48 publications

Endoplasmic reticulum stress and the unfolded protein response in disorders of myelinating glia

Endoplasmic reticulum stress and the unfolded protein response in disorders of myelinating glia

Endoplasmic reticulum stress in disorders of myelinating cells

The unfolded protein response in multiple sclerosis

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