Apoptotic death of neurons exhibiting peripherin aggregates is mediated by the proinflammatory cytokine tumor necrosis factor-α

Peripherin, a neuronal intermediate filament protein associated with axonal spheroids in amyotrophic lateral sclerosis (ALS), induces the selective degeneration of motor neurons when overexpressed in transgenic mice. To further clarify the selectivity and mechanism of peripherin-induced neuronal death, we analyzed the effects of peripherin overexpression in primary neuronal cultures. Peripherin overexpression led to the formation of cytoplasmic protein aggregates and caused the death not only of motor neurons, but also of dorsal root ganglion (DRG) neurons that were cultured from dissociated spinal cords of peripherin transgenic embryos. Apoptosis of DRG neurons containing peripherin aggregates was dependent on the proinflammatory central nervous system environment of spinal cultures, rich in activated microglia, and required TNF-α. This synergistic proapoptotic effect may contribute to neuronal selectivity in ALS.

• Publication year

  2001

• Venue

  Journal of Cell Biology

• Publication date

  2001-10-15

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1083/jcb.200107058PMID 11604419PMCID 2198840
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• beta-Amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis.

  2001cited by this paper
• Increased chemokine gene expression during aging in the murine brain.

  2001cited by this paper
• β-Amyloid Stimulation of Microglia and Monocytes Results in TNFα-Dependent Expression of Inducible Nitric Oxide Synthase and Neuronal Apoptosis

  2001influential reference
• Glial involvement in the degeneration process of Lewy body-bearing neurons and the degradation process of Lewy bodies in brains of dementia with Lewy bodies.

  2001cited by this paper
• Inhibition of Aberrant and Constitutive Phosphorylation of the High‐Molecular‐Mass Neurofilament Subunit by CEP‐1347 (KT7515), an Inhibitor of the Stress‐Activated Protein Kinase Signaling Pathway

  2000cited by this paper
• Formation of Intermediate Filament Protein Aggregates with Disparate Effects in Two Transgenic Mouse Models Lacking the Neurofilament Light Subunit

  2000cited by this paper
• Tumor necrosis factor-alpha induces neuronal death by silencing survival signals generated by the type I insulin-like growth factor receptor.

  2000cited by this paper
• Apoptosis in neural development and disease.

  2000cited by this paper
• Circulating levels of tumour necrosis factor-alpha and its soluble receptors are increased in the blood of patients with amyotrophic lateral sclerosis.

  2000cited by this paper
• Tumor Necrosis Factor‐α Induces Neuronal Death by Silencing Survival Signals Generated by the Type I Insulin‐Like Growth Factor Receptor

  2000cited by this paper
• Interactions between peripherin and neurofilaments in cultured cells: disruption of peripherin assembly by the NF-M and NF-H subunits.

  1999influential reference
• TNF-α Induces Actin Cytoskeleton Reorganization in Glomerular Epithelial Cells Involving Tyrosine Phosphorylation of Paxillin and Focal Adhesion Kinase

  1999cited by this paper
• Extra neurofilament NF-L subunits rescue motor neuron disease caused by overexpression of the human NF-H gene in mice.

  1999cited by this paper
• The Intermediate Filament Protein Peripherin Is the Specific Interaction Partner of Mouse BPAG1-n (Dystonin) in Neurons

  1999cited by this paper
• Increased microglial activation and protein nitration in white matter of the aging monkey.

  1999cited by this paper
• Reactive microgliosis.

  1999influential reference
• Up‐Regulation of Protein Chaperones Preserves Viability of Cells Expressing Toxic Cu/Zn‐Superoxide Dismutase Mutants Associated with Amyotrophic Lateral Sclerosis

  1999influential reference
• Late Onset Death of Motor Neurons in Mice Overexpressing Wild-Type Peripherin

  1999influential reference
• Cytokine transcripts expressed by microglia in vitro are not expressed by ameboid microglia of the developing rat central nervous system

  1999cited by this paper
• Lipopolysaccharide-induced microglial activation in culture: temporal profiles of morphological change and release of cytokines and nitric oxide.

  1999cited by this paper
• Mechanisms of tumor necrosis factor alpha action on neurodegeneration: interaction with insulin-like growth factor-1.

  1999cited by this paper
• The mosaic of brain glial hyperactivity during normal ageing and its attenuation by food restriction.

  1999cited by this paper
• Neurons undergo apoptosis in animal and cell culture models of diabetes.

  1999cited by this paper
• Peripherin Is Tyrosine‐Phosphorylated at Its Carboxyl‐Terminal Tyrosine

  1998cited by this paper
• Nitration of the low molecular weight neurofilament is equivalent in sporadic amyotrophic lateral sclerosis and control cervical spinal cord.

  1998cited by this paper
• Caspases: enemies within.

  1998cited by this paper
• Glutamate Potentiates the Toxicity of Mutant Cu/Zn-Superoxide Dismutase in Motor Neurons by Postsynaptic Calcium-Dependent Mechanisms

  1998influential reference
• Circulating Antibody against Tumor Necrosis Factor–Alpha Protects Rat Brain from Reperfusion Injury

  1998cited by this paper
• Ischemic and Excitotoxic Brain Injury is Enhanced in Mice Lacking the p55 Tumor Necrosis Factor Receptor

  1998cited by this paper
• Protective effect of neurofilament heavy gene overexpression in motor neuron disease induced by mutant superoxide dismutase.

  1998cited by this paper
• Tumor necrosis factor alpha.

  1998influential reference
• Expression of Pro‐Inflammatory Cytokine and Chemokine mRNA Upon Experimental Spinal Cord Injury in Mouse: an In Situ Hybridization Study

  1997cited by this paper
• Neuritic plaque evolution in Alzheimer’s disease is accompanied by transition of activated microglia from primed to enlarged to phagocytic forms

  1997influential reference
• Elevated free nitrotyrosine levels, but not protein-bound nitrotyrosine or hydroxyl radicals, throughout amyotrophic lateral sclerosis (ALS)-like disease implicate tyrosine nitration as an aberrant in vivo property of one familial ALS-linked superoxide dismutase 1 mutant.

  1997cited by this paper
• Apoptosis in neural development and disease

  1997cited by this paper
• Aggregation of Mutant Cu/Zn Superoxide Dismutase Proteins in a Culture Model of ALS

  1997cited by this paper
• Activated microglial cells are colocalized with perivascular deposits of amyloid-beta protein in Alzheimer's disease brain.

  1997cited by this paper
• Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury.

  1997cited by this paper
• Deficient activation of microglia during optic nerve degeneration.

  1996cited by this paper
• Transgenic mice carrying a human mutant superoxide dismutase transgene develop neuronal cytoskeletal pathology resembling human amyotrophic lateral sclerosis lesions.

  1996cited by this paper
• Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors

  1996cited by this paper
• Activation of microglial cells by beta-amyloid protein and interferon-gamma.

  1995cited by this paper
• Microglia: intrinsic immuneffector cell of the brain.

  1995cited by this paper
• Interleukin-1 and tumor necrosis factor-alpha synergistically mediate neurotoxicity: involvement of nitric oxide and of N-methyl-D-aspartate receptors.

  1995cited by this paper
• The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases.

  1995influential reference
• Antibodies against microglia/brain macrophages in the cerebrospinal fluid of a patient with acute amyotrophic lateral sclerosis and presenile dementia.

  1995cited by this paper
• Apoptosis, oncosis, and necrosis. An overview of cell death.

  1995cited by this paper
• Tumor necrosis factors alpha and beta protect neurons against amyloid beta-peptide toxicity: evidence for involvement of a kappa B-binding factor and attenuation of peroxide and Ca2+ accumulation.

  1995cited by this paper
• Increasing neurofilament subunit NF-M expression reduces axonal NF-H, inhibits radial growth, and results in neurofilamentous accumulation in motor neurons

  1995cited by this paper
• Cytokines and the nervous system. I: Expression and recognition.

  1995cited by this paper
• Tumor necrosis factor-α (TNF-α) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients

  1994cited by this paper
• The role of calcium‐binding proteins in selective motoneuron vulnerability in amyotrophic lateral sclerosis

  1994cited by this paper
• Tumor necrosis factor-alpha potentiates glutamate neurotoxicity in human fetal brain cell cultures.

  1994cited by this paper
• Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson's disease.

  1994cited by this paper
• Tumor necrosis factors protect neurons against metabolic-excitotoxic insults and promote maintenance of calcium homeostasis.

  1994cited by this paper
• Cellular forms and functions of brain microglia.

  1994cited by this paper
• Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients.

  1994cited by this paper
• The significance of changes in serum tumour necrosis factor (TNF) activity in severely burned patients.

  1994cited by this paper
• Peroxynitrite versus Hydroxyl Radical: The Role of Nitric Oxide in Superoxide‐Dependent Cerebral Injury a

  1994cited by this paper
• Synthesis of nitric oxide in CNS glial cells

  1993cited by this paper
• Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease

  1993influential reference
• Peripherin immunoreactive structures in amyotrophic lateral sclerosis.

  1993cited by this paper
• Macrophages and inflammation in the central nervous system.

  1993cited by this paper
• Parvalbumin and calbindin D‐28k in the human motor system and in motor neuron disease

  1993cited by this paper
• Peripherin and Neurofilament Protein Coexist in Spinal Spheroids of Motor Neuron Disease

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• Macrophage‐induced cytotoxicity of N‐methyl‐D‐aspartate receptor positive neurons involves excitatory amino acids rather than reactive oxygen intermediates and cytokines

  1992cited by this paper
• Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation

  1992cited by this paper
• Induction of calcium-independent nitric oxide synthase activity in primary rat glial cultures.

  1992cited by this paper
• Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue.

  1992influential reference
• Tumor necrosis factor facilitates regeneration of injured central nervous system axons.

  1991cited by this paper
• Elevated circulating tumor necrosis factor levels in Alzheimer's disease.

  1991influential reference
• Tumor necrosis factor-a

  1991cited by this paper
• Differential regulation of peripherin and neurofilament gene expression in regenerating rat DRG neurons

  1990influential reference
• Differential expression of two neuronal intermediate-filament proteins, peripherin and the low-molecular-mass neurofilament protein (NF-L), during the development of the rat

  1990cited by this paper
• Regulation of peripherin and neurofilament expression in regenerating rat motor neurons.

  1990influential reference
• Selective distribution of the 57 kDa neural intermediate filament protein in the rat CNS

  1989cited by this paper
• Distribution of a novel 57 kDa intermediate filament (IF) protein in the nervous system

  1988cited by this paper
• Tumor Necrosis Factors Alpha and Beta

  1988cited by this paper
• Size‐dependent myelinated fiber loss in the corticospinal tract in Shy‐Drager syndrome and amyotrophic lateral sclerosis

  1987cited by this paper
• Morphometric Comparison of the Vulnerability of Peripheral Motor and Sensory Neurons in Amyotrophic Lateral Sclerosis

  1981cited by this paper
• Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation

  1980cited by this paper

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  2018cites this paper
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• Molecular Mechanisms of Inflammation in Stroke

  2017cites this paper
• Translational Research in Stroke

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• Chapter 19 Intermediate Filaments in Neurodegenerative Diseases

  2017cites this paper
• α-Internexin and Peripherin: Expression, Assembly, Functions, and Roles in Disease.

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• ALS mouse model SOD1G93A displays early pathology of sensory small fibers associated to accumulation of a neurotoxic splice variant of peripherin.

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• Angelica Sinensis attenuates inflammatory reaction in experimental rat models having spinal cord injury.

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• Studies of selective TNF inhibitors in the treatment of brain injury from stroke and trauma: a review of the evidence to date

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• Mechanically assisted cough in motor neurone disease

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• The effects of diabetes on sympathetic neurovascular transmission

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• Real‐time imaging reveals defects of fast axonal transport induced by disorganization of intermediate filaments

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• Chapter 4 Molecular mechanisms of motor neuron degeneration in amyotrophic lateral sclerosis.

  2007cites this paper
• Altered in-vitro and in-vivo expression of glial glutamate transporter-1 following exposure to cerebrospinal fluid of amyotrophic lateral sclerosis patients.

  2007cites this paper
• Chapter 6 Animal models of motor neuron death.

  2007influential citation
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  2007cites this paper
• Absence of Tumor Necrosis Factor-α Does Not Affect Motor Neuron Disease Caused by Superoxide Dismutase 1 Mutations

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• Transgenic mouse models of amyotrophic lateral sclerosis.

  2006cites this paper
• Neuronal intermediate filaments and ALS: a new look at an old question.

  2006influential citation
• Human coronavirus OC43 infection induces chronic encephalitis leading to disabilities in BALB/C mice

  2006cites this paper
• Genetics of familial and sporadic amyotrophic lateral sclerosis.

  2006cites this paper
• Strategies to prevent motoneuron degeneration in models of Amyotrophic Lateral Sclerosis.

  2006cites this paper
• Defective axonal transport of neurofilament proteins in neurons overexpressing peripherin

  2006cites this paper
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  2006cites this paper
• Role of neurofilament aggregation in motor neuron disease

  2006cites this paper
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  2006cites this paper
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  2005cites this paper
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  2005cites this paper
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  2005cites this paper
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  2005cites this paper
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  2005cites this paper
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