Glial Contributions to Neural Function and Disease

Rasband, Matthew N.

doi:10.1074/mcp.r115.053744

Cited by 52 publications

(53 citation statements)

References 66 publications

(55 reference statements)

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“…However, apparent clinical symptoms are manifested only after extensive pathological damage, with significant neuronal and synaptic loss. Eventually, the contribution of individual insults reaches a common end state, which causes severe impairments in the function and plasticity of neuronal and glial cells (Rasband, 2016). Over the past few decades, there has been considerable effort to understand the pathogenesis of NDs.…”

Section: Introductionmentioning

confidence: 99%

TRP Channels as Emerging Therapeutic Targets for Neurodegenerative Diseases

et al. 2020

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The development of treatment for neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis is facing medical challenges due to the increasingly aging population. However, some pharmaceutical companies have ceased the development of therapeutics for NDs, and no new treatments for NDs have been established during the last decade. The relationship between ND pathogenesis and risk factors has not been completely elucidated. Herein, we review the potential involvement of transient receptor potential (TRP) channels in NDs, where oxidative stress and disrupted Ca 2+ homeostasis consequently lead to neuronal apoptosis. Reactive oxygen species (ROS) -sensitive TRP channels can be key risk factors as polymodal sensors, since progressive late onset with secondary pathological damage after initial toxic insult is one of the typical characteristics of NDs. Recent evidence indicates that the dysregulation of TRP channels is a missing link between disruption of Ca 2+ homeostasis and neuronal loss in NDs. In this review, we discuss the latest findings regarding TRP channels to provide insights into the research and quests for alternative therapeutic candidates for NDs. As the structures of TRP channels have recently been revealed by cryo-electron microscopy, it is necessary to develop new TRP channel antagonists and reevaluate existing drugs.

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Section: Introductionmentioning

confidence: 99%

TRP Channels as Emerging Therapeutic Targets for Neurodegenerative Diseases

et al. 2020

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“…Neurons and glial cells are 2 major types of cells in the central nervous system (CNS) [1]. Glioma, a type of tumor that originates from glial cells, is usually found in the brain and occasionally in the spinal cord.…”

Section: Introductionmentioning

confidence: 99%

Valproic acid-induced amphiregulin secretion confers resistance to temozolomide treatment in human glioma cells

Chen¹,

Lee²,

Huang³

et al. 2019

BMC Cancer

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Background: Glioblastoma multiforme (GBM) is the most severe type of primary brain tumor with a high mortality rate. Although extensive treatments for GBM, including resection, irradiation, chemotherapy and immunotherapy, have been tried, the prognosis is still poor. Temozolomide (TMZ), an alkylating agent, is a front-line chemotherapeutic drug for the clinical treatment of GBM; however, its effects are very limited because of the chemoresistance. Valproic acid (VPA), an antiepileptic agent with histone deacetylase inhibitor activity, has been shown to have synergistic effects with TMZ against GBM. The mechanism of action of VPA on TMZ combination therapy is still unclear. Accumulating evidence has shown that secreted proteins are responsible for the cross talking among cells in the tumor microenvironment, which may play a critical role in the regulation of drug responses. Methods: To understand the effect of VPA on secreted proteins in GBM cells, we first used the antibody array to analyze the cell culture supernatant from VPA-treated and untreated GBM cells. The results were further confirmed by lentivirus-mediated knockdown and exogenous recombinant administration. Results: Our results showed that amphiregulin (AR) was highly secreted in VPA-treated cells. Knockdown of AR can sensitize GBM cells to TMZ. Furthermore, pretreatment of exogenous recombinant AR significantly increased EGFR activation and conferred resistance to TMZ. To further verify the effect of AR on TMZ resistance, cells pre-treated with AR neutralizing antibody markedly increased sensitivity to TMZ. In addition, we also observed that the expression of AR was positively correlated with the resistance of TMZ in different GBM cell lines. Conclusions: The present study aimed to identify the secreted proteins that contribute to the modulation of drug response. Understanding the full set of secreted proteins present in glial cells might help reveal potential therapeutic opportunities. The results indicated that AR may potentially serve as biomarker and therapeutic approach for chemotherapy regimens in GBM.

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“…These cells play critical functional roles in nervous systems, including synaptic maturation and function, blood-brain-barrier integrity, and myelination. Rasband (14) highlights the diversity of glial types as well as their functions in health and role in neurological diseases in this issue. Intriguingly, interactions between subcellular domains of oligodendrocytes or Schwann cells with axons helps craft nodes of Ranvier in the CNS and PNS, subcellular domains along axons that are essential for the accelerated conduction velocities that myelin conveys to neurons.…”

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confidence: 99%

Neuroproteomics: How Many Angels can be Identified in an Extract from the Head of a Pin?

Twiss

Fainzilber

2016

Molecular & Cellular Proteomics

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Oscar Wilde once defined fox hunting as an activity of "the unspeakable in pursuit of the uneatable." This sentiment may well reflect the reaction of some mass spectrometry laboratories to neuroscience colleagues rushing in with a vial containing a hopelessly inadequate amount of sample originating from a tissue of intractable complexity, or in other words a neuroproteomics project. This issue of Molecular and Cellular Proteomics focuses on application of proteomics to current problems in neuroscience. Although some neuroscientists have ventured into proteomics, most of the neuroscience community has yet to embrace proteomics approaches. Despite increasing interest and awareness of the potential of such approaches (1, 2), many neuroscientists are still in the early stages of a learning curve on how proteomics approaches can be leveraged for new insights and knowledge in their field. Conversely, many proteomics laboratories are not aware of the daunting complexity and limited quantities of samples derived from neural tissues. The review and commentary papers presented in this issue highlight current issues in neuroscience that may now be ready for interrogation by modern proteomics approaches. The primary research papers in this issue provide examples of success in overcoming the many hurdles of neuroproteomics projects, and the exciting new insights that such achievements bring.Despite advances in sensitivity in mass spectrometry (MS), protein yield from neural tissues is often a harsh limiting factor when considering the quantities needed for proteomics. Both the central and peripheral nervous systems (CNS 1 and PNS, respectively) are composed of mixtures of different cell types with intricate architecture and connectivity, presenting major sampling and analysis challenges. These challenges typically require separation of different cell types prior to proteomics, thereby further limiting sample size, or trying to infer cell-type specific changes from tissue lysates. The cover of this issueshows an example of such cellular complexity, illustrating the composition of the mammalian retina with photoreceptors, glia, and neurons assembled into complex layers that are essential for vision. The intricate cytoplasmic extensions of the glial and neuronal cells within the retina, and the axonal extensions from the retina to the brain, add additional layers of complexity that are not depicted in the image. This juxtaposition of different cell types and subtypes, and the intertwined cytoplasmic processes of neurons and glial cells, presents a daunting challenge for proteomics of different neuronal and glial cell types. The work by Grosche et al. (3) in this issue tackled the complexity of the retina with a unique fractionation approach tailored to isolate and dissect the proteome of the Mueller glial cells, a specialized glial cell population unique to the retina. Quantitative mass spectrometry on Muller cell enriched versus depleted fractions enabled the authors to identify specific functions of this glial population in ...

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Glial Contributions to Neural Function and Disease

Cited by 52 publications

References 66 publications

TRP Channels as Emerging Therapeutic Targets for Neurodegenerative Diseases

TRP Channels as Emerging Therapeutic Targets for Neurodegenerative Diseases

Valproic acid-induced amphiregulin secretion confers resistance to temozolomide treatment in human glioma cells

Neuroproteomics: How Many Angels can be Identified in an Extract from the Head of a Pin?

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