The role of TNF and its receptors in Alzheimer's disease

Perry, Rodney T.; Collins, Julianne S.; Wiener, Howard W.; Acton, Ronald T.; Go, Rodney C.P.

doi:10.1016/s0197-4580(01)00291-3

Cited by 243 publications

(157 citation statements)

References 133 publications

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“…It is produced as a membrane-bound 26-kDa precursor molecule that is cleaved by the TNF converting enzyme to produce a 17-kDa active cytokine. 9 Because of the low levels of TNF expression in the healthy brain, it has been difficult to determine its precise role in physiological conditions. In inflammatory or disease states, TNF along with several other proinflammatory mediators and neurotoxic substances is produced predominantly by activated microglia.…”

Section: Tumor Necrosis Factor-␣mentioning

confidence: 99%

Involvement of Pro- and Anti-Inflammatory Cytokines and Chemokines in the Pathophysiology of Traumatic Brain Injury

2010

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Summary:Despite dramatic improvements in the management of traumatic brain injury (TBI), to date there is no effective treatment available to patients, and morbidity and mortality remain high. The damage to the brain occurs in two phases, the initial primary phase being the injury itself, which is irreversible and amenable only to preventive measures to minimize the extent of damage, followed by an ongoing secondary phase, which begins at the time of injury and continues in the ensuing days to weeks. This delayed phase leads to a variety of physiological, cellular, and molecular responses aimed at restoring the homeostasis of the damaged tissue, which, if not controlled, will lead to secondary insults. The development of secondary brain injury represents a window of opportunity in which pharmaceutical compounds with neuroprotective properties could be administered. To establish effective treatments for TBI victims, it is imperative that the complex molecular cascades contributing to secondary injury be fully elucidated. One pathway known to be activated in response to TBI is cellular and humoral inflammation. Neuroinflammation within the injured brain has long been considered to intensify the damage sustained following TBI. However, the accumulated findings from years of clinical and experimental research support the notion that the action of inflammation may differ in the acute and delayed phase after TBI, and that maintaining limited inflammation is essential for repair. This review addresses the role of several cytokines and chemokines following focal and diffuse TBI, as well as the controversies around the use of therapeutic anti-inflammatory treatments versus genetic deletion of cytokine expression.

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Section: Tumor Necrosis Factor-␣mentioning

confidence: 99%

Involvement of Pro- and Anti-Inflammatory Cytokines and Chemokines in the Pathophysiology of Traumatic Brain Injury

2010

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“…For example, it has been hypothesized that proinflammatory cytokines, such as interleukin-1 and tumour necrosis factor-a (TNF-a), could partly promote neurodegenerative processes depending upon bAP. 7,8 TNF-related apoptosis-inducing ligand (TRAIL) is a novel peptide molecule belonging to the TNF family whose main role is to induce programmed cell death in tumour cell lines from various tissue origins. 9 TRAIL binds to five specific receptors of the TNF/NGF family.…”

Section: Introductionmentioning

confidence: 99%

Neutralization of TRAIL death pathway protects human neuronal cell line from β-amyloid toxicity

et al. 2003

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Here we report that a novel member of the TNF-a family, TNF-related apoptosis-inducing ligand (TRAIL), contributes substantially to amyloid-induced neurotoxicity in human SH-SY5Y neuronal cell line. Involvement of TRAIL in the amyloidinduced cell death is supported by cDNA array, Northern blot, and Western blot data, demonstrating increased TRAIL expression after treatment of the cells with a neurotoxic fragment of amyloid protein (bAP). TRAIL was also found to be released in the culture media after bAP treatment with a time-course overlapping to contents of the intracellular protein. Contribution of TRAIL to bAP neurotoxicity is demonstrated by data showing that TRAIL-neutralizing monoclonal antibody protects neuronal SH-SY5Y cells from bAP neurotoxicity. Moreover, exposure of neuronal SH-SY5Y cells to TRAIL leads to cell death, indicating that this substance per se is endowed with neurotoxic properties. We also found that, similarly to bAP and TRAIL, activation of the death-domain adaptor protein FADD results in neuronal cell death. Lack of FADD function, by overexpression of its dominant negative, rescued cells from either TRAIL-or bAP-induced neurotoxicity, supporting the hypothesis that these three molecules share common intracellular pathways. Finally, we found that bAP strongly activated caspase-8, and the cell-permeable, selective caspase-8 inhibitor z-IETD-FMK prevents both bAP-and TRAIL-induced neurotoxicity. In view of TRAIL's potency in inducing neuronal death, and its role as mediator of bAP, it is plausible to hypothesize that TRAIL can be regarded as a molecule that provides substantial contribution to bAP-dependent cell death, which takes part in the progression of the neurodegenerative process and related chronic inflammatory response.

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“…Tumor necrosis factor (TNF)-␣ is a prominent proinflammatory cytokine that has been associated with various neurodegenerative diseases (Tyor et al, 1995;Clark and Lutsep, 2001;Lou et al, 2001;Perry et al, 2001;Probert and Akassoglou, 2001;Shinoda et al, 2003). Its function in the pathogenesis of neural injury remains unclear, however, because both neurotoxic and neuroprotective effects after injury have been described (Bruce et al, 1996;Nawashiro et al, 1997;Kim et al, 2001;Martin-Villalba et al, 2001;Yang et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Tumor Necrosis Factor Receptor 1 and Its Signaling Intermediates Are Recruited to Lipid Rafts in the Traumatized Brain

Lotocki¹,

Alonso

Dietrich³

et al. 2004

J. Neurosci.

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The tumor necrosis factor (TNF) ligand-receptor system plays an essential role in apoptosis that contributes to secondary damage after traumatic brain injury (TBI). TNF also stimulates inflammation by activation of gene transcription through the IB kinase (IKK)/NF-B and JNK (c-Jun N-terminal protein kinase)/AP-1 signaling cascades. The mechanism by which TNF signals between cell death and survival and the role of receptor localization in the activation of downstream signaling events are not fully understood. Here, TNF receptor 1 (TNFR1) signaling complexes in lipid rafts were investigated in the cerebral cortex of adult male Sprague Dawley rats subjected to moderate (1.8 -2.2 atmospheres) fluid-percussion TBI and naive controls. In the normal rat cortex, a portion of TNFR1 was present in lipid raft microdomains, where it associated with the adaptor proteins TRADD (TNF receptor-associated death domain), TNF receptorassociated factor-2 (TRAF-2), the Ser/Thr kinase RIP (receptor-interacting protein), TRAF1, and cIAP-1 (cellular inhibitor of apoptosis protein-1), forming a survival signaling complex. Moderate TBI resulted in rapid recruitment of TNFR1, but not TNFR2 or Fas, to lipid rafts and induced alterations in the composition of signaling intermediates. TNFR1 and TRAF1 were polyubiquitinated in lipid rafts after TBI. Subsequently, the signaling complex contained activated caspase-8, thus initiating apoptosis. In addition, TBI caused a transient activation of NF-B, but receptor signaling interacting proteins IKK␣ and IKK␤ were not detected in raft-containing fractions. Thus, redistribution of TNFR1 in lipid rafts and nonraft regions of the plasma membrane may regulate the diversity of signaling responses initiated by these receptors in the normal brain and after TBI.

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The role of TNF and its receptors in Alzheimer's disease

Cited by 243 publications

References 133 publications

Involvement of Pro- and Anti-Inflammatory Cytokines and Chemokines in the Pathophysiology of Traumatic Brain Injury

Involvement of Pro- and Anti-Inflammatory Cytokines and Chemokines in the Pathophysiology of Traumatic Brain Injury

Neutralization of TRAIL death pathway protects human neuronal cell line from β-amyloid toxicity

Tumor Necrosis Factor Receptor 1 and Its Signaling Intermediates Are Recruited to Lipid Rafts in the Traumatized Brain

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