Neuronal endoplasmic reticulum stress in axon injury and neurodegeneration

Li, Shaohua; Liu, Yang; Selzer, Michael E.; Hu, Yang

doi:10.1002/ana.24005

Cited by 52 publications

(46 citation statements)

References 97 publications

(239 reference statements)

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“…Neuronal damage induced by peripheral or central axonal injury comprises unfolded protein response and ER stress that can promote a regenerative response or apoptotic cell death (45,46). Salubrinal provides neuroprotection by inhibition of phosphorylated-eukaryotic initiation factor 2 dephosphorylation and ER stress (47) and salubrinal treatment results in attenuation of microgliosis and neurodegeneration in mice with superoxide dismutase (SOD1) mutated with substitution of glycine to alanine at position 93 (48).…”

Section: Glial Reactivity and C-bouton Plasticity After Reversible Anmentioning

confidence: 99%

Localization and dynamic changes of neuregulin‐1 at C‐type synaptic boutons in association with motor neuron injury and repair

et al. 2019

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C‐type synaptic boutons (C‐boutons) provide cholinergic afferent input to spinal cord motor neurons (MNs), which display an endoplasmic reticulum (ER)–related subsurface cistern (SSC) adjacent to their postsynaptic membrane. A constellation of postsynaptic proteins is clustered at C‐boutons, including M2 muscarinic receptors, potassium channels, and σ‐1 receptors. In addition, we previously found that neuregulin (NRG)1 is associated with C‐boutons at postsynaptic SSCs, whereas its ErbB receptors are located in the presynaptic compartment. C‐bouton–mediated regulation of MN excitability has been implicated in MN disease, but NRG1‐mediated functions and the impact of various pathologic conditions on C‐bouton integrity have not been studied in detail. Here, we investigated changes in C‐boutons after electrical stimulation, pharmacological treatment, and peripheral nerve axotomy. SSC‐linked NRG1 clusters were severely disrupted in acutely stressed MNs and after tunicamycin‐induced ER stress. In axotomized MNs, C‐bouton loss occurred in concomitance with microglial recruitment and was prevented by the ER stress inhibitor salubrinal. Activated microglia displayed a positive chemotaxis to C‐boutons. Analysis of transgenic mice overexpressing NRG1 type I and type III isoforms in MNs indicated that NRG1 type III acts as an organizer of SSC‐like structures, whereas NRG1 type I promotes synaptogenesis of presynaptic cholinergic terminals. Moreover, MN‐derived NRG1 signals may regulate the activity of perineuronal microglial cells. Together, these data provide new insights into the molecular and cellular pathology of C‐boutons in MN injury and suggest that distinct NRG1 isoform–mediated signaling functions regulate the complex matching between pre‐ and postsynaptic C‐bouton elements.—Salvany, S., Casanovas, A., Tarabal, O., Piedrafita, L., Hernández, S., Santafé, M., Soto‐Bernardini, M. C., Calderó, J., Schwab, M. H., Esquerda, J. E. Localization and dynamic changes of neuregulin‐1 at C‐type synaptic boutons in association with motor neuron injury and repair. FASEB J. 33, 7833–7851 (2019). http://www.fasebj.org

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Section: Glial Reactivity and C-bouton Plasticity After Reversible Anmentioning

confidence: 99%

Localization and dynamic changes of neuregulin‐1 at C‐type synaptic boutons in association with motor neuron injury and repair

et al. 2019

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“…when mis-folded proteins accumulate continuously, they overload the ER, and apoptotic cell death often ensues [4]. The ER stress response is characterized by changes in specific proteins (GRP78, ATF6, XBP-1 and apoptosis protein CHOP and caspase-12), which cause translational attenuation, induction of ER chaperones, and degradation of mis-folded proteins [5,6].…”

mentioning

confidence: 99%

Inhibition of Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of bFGF in the 6-OHDA-Induced Parkinson’s Disease Model

Cai¹,

Ye²,

Zhu³

et al. 2016

Aging and disease

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Parkinson's disease (PD) is a progressive neurodegenerative disorder with complicated pathophysiologic mechanisms. Endoplasmic reticulum (ER) stress appears to play a critical role in the progression of PD. We demonstrated that basic fibroblast growth factor (bFGF), as a neurotropic factor, inhibited ER stress-induced neuronal cell apoptosis and that 6-hydroxydopamine (6-OHDA)-induced ER stress was involved in the progression of PD in rats. bFGF administration improved motor function recovery, increased tyrosine hydroxylase (TH)-positive neuron survival, and upregulated the levels of neurotransmitters in PD rats. The 6-OHDA-induced ER stress response proteins were inhibited by bFGF treatment. Meanwhile, bFGF also increased expression of TH. The administration of bFGF activated the downstream signals PI3K/Akt and Erk1/2 in vivo and in vitro. Inhibition of the PI3K/Akt and Erk1/2 pathways by specific inhibitors partially reduced the protective effect of bFGF. This study provides new insight towards bFGF translational drug development for PD involving the regulation of ER stress.

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“…The rotational and acceleration/deceleration components of blast-induced TBI, commonly tears axons apart leading to a robust gliosis response and axonal degeneration (34, 56, 95). Axonal swelling and bulb formation are common morphological hallmarks observed following TBI and contribute to decreased action potential firing (44, 45).…”

Section: Traumatic Brain Injury Effects On Neuronsmentioning

confidence: 99%

Role of Microvascular Disruption in Brain Damage from Traumatic Brain Injury

Logsdon

Lucke‐Wold

Turner

et al. 2015

Comprehensive Physiology

125

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Traumatic brain injury (TBI) is acquired from an external force, which can inflict devastating effects to the brain vasculature and neighboring neuronal cells. Disruption of vasculature is a primary effect that can lead to a host of secondary injury cascades. The primary effects of TBI are rapidly occurring while secondary effects can be activated at later time points and may be more amenable to targeting. Primary effects of TBI include diffuse axonal shearing, changes in blood brain barrier (BBB) permeability, and brain contusions. These mechanical events, especially changes to the BBB, can induce calcium perturbations within brain cells producing secondary effects, which include cellular stress, inflammation, and apoptosis. These secondary effects can be potentially targeted to preserve the tissue surviving the initial impact of TBI. In the past, TBI research had focused on neurons without any regard for glial cells and the cerebrovasculature. Now a greater emphasis is being placed on the vasculature and the neurovascular unit following TBI. A paradigm shift in the importance of the vascular response to injury has opened new avenues of drug treatment strategies for TBI. However, a connection between the vascular response to TBI and the development of chronic disease has yet to be elucidated. Long-term cognitive deficits are common amongst those sustaining severe or multiple mild TBIs. Understanding the mechanisms of cellular responses following TBI is important to prevent the development of neuropsychiatric symptoms. With appropriate intervention following TBI, the vascular network can perhaps be maintained and the cellular repair process possibly improved to aid in the recovery of cellular homeostasis.

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Neuronal endoplasmic reticulum stress in axon injury and neurodegeneration

Cited by 52 publications

References 97 publications

Localization and dynamic changes of neuregulin‐1 at C‐type synaptic boutons in association with motor neuron injury and repair

Localization and dynamic changes of neuregulin‐1 at C‐type synaptic boutons in association with motor neuron injury and repair

Inhibition of Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of bFGF in the 6-OHDA-Induced Parkinson’s Disease Model

Role of Microvascular Disruption in Brain Damage from Traumatic Brain Injury

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