Dexamethasone Inhibits TNF-α Synthesis More Effectively in Alzheimer’s Disease Patients than in Healthy Individuals

Dziedzic, Tomasz; Wybrańska, Iwona; Dembińska-Kieć, A.; Klimkowicz, Aleksandra; Słowik, Agnieszka; Pankiewicz, Joanna; Zdzienicka, Anna; Szczudlik, Andrzej

doi:10.1159/000072814

Cited by 11 publications

(7 citation statements)

References 19 publications

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“…Inflammation and glial activation in neurodegenerative diseases: AD Age is the major risk factor for AD (Katzman 1986). Epidemiological evidence (Dziedzic et al 2003;Sala et al 2003) as well as that obtained using experimental models of AD (Griffin and Mrak 2002;Melton et al 2003) show that pro-inflammatory conditions promote the development and progression of AD (Akiyama et al 2000;Lim et al 2000;Neuroinflammation Working Group 2000). Non-steroidal anti-inflammatory drugs decrease the risk of AD or delay its onset (Stewart et al 1997;Broe et al 2000;Etminan et al 2003).…”

Section: Microglial Cell Reactivity and Diseasementioning

confidence: 98%

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Aging‐dependent changes of microglial cells and their relevance for neurodegenerative disorders

Bernhardi

Tichauer

Eugenı́n

2010

Journal of Neurochemistry

214

176

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J. Neurochem. (2010) 112, 1099–1114. Abstract Among multiple structural and functional brain changes, aging is accompanied by an increase of inflammatory signaling in the nervous system as well as a dysfunction of the immune system elsewhere. Although the long‐held view that aging involves neurocognitive impairment is now dismissed, aging is a major risk factor for neurodegenerative diseases such as Alzheimer`s disease, Parkinson`s disease and Huntington’s disease, among others. There are many age‐related changes affecting the brain, contributing both to certain declining in function and increased frailty, which could singly and collectively affect neuronal viability and vulnerability. Among those changes, both inflammatory responses in aged brains and the altered regulation of toll like receptors, which appears to be relevant for understanding susceptibility to neurodegenerative processes, are linked to pathogenic mechanisms of several diseases. Here, we review how aging and pro‐inflammatory environment could modulate microglial phenotype and its reactivity and contribute to the genesis of neurodegenerative processes. Data support our idea that age‐related microglial cell changes, by inducing cytotoxicity in contrast to neuroprotection, could contribute to the onset of neurodegenerative changes. This view can have important implications for the development of new therapeutic approaches.

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Section: Microglial Cell Reactivity and Diseasementioning

confidence: 98%

“…Age is the major risk factor for AD (Katzman 1986). Epidemiological evidence (Dziedzic et al. 2003; Sala et al.…”

Section: Microglial Cell Reactivity and Diseasementioning

confidence: 99%

Aging‐dependent changes of microglial cells and their relevance for neurodegenerative disorders

Bernhardi

Tichauer

Eugenı́n

2010

Journal of Neurochemistry

214

176

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“…Pilot experiments were conducted with dexamethasone (10 µM) on LPS-challenged whole blood samples from AD patients and healthy subjects. The authors reported that dexamethasone was more efficient on AD samples vs. controls [168]. Interestingly, dexamethasone is commonly co-administered with thalidomide analogs in cancer treatment (see section 5.8 below) because a cumulative effect on inflammation reduction was noted during clinical trials.…”

Section: Strategies and Challenges Involving Central Tnf-α Signalimentioning

confidence: 99%

“…Interestingly, dexamethasone is commonly co-administered with thalidomide analogs in cancer treatment (see section 5.8 below) because a cumulative effect on inflammation reduction was noted during clinical trials. However, long term administration of corticoids often results in adverse events such as increased risks of infection, osteoporosis, and mental depression via alteration of the hypothalamic-pituitaryadrenal (HPA) axis [168, 169], limiting their potential to treat chronic disorders like AD.…”

Section: Strategies and Challenges Involving Central Tnf-α Signalimentioning

confidence: 99%

Targeting Tumor Necrosis Factor Alpha for Alzheimer’s Disease

Decourt¹,

Lahiri

Sabbagh

2017

CAR

311

212

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Alzheimer’s disease (AD) affects an estimated 44 million individuals worldwide, yet no therapeutic intervention is available to stop the progression of the dementia. Neuropathological hallmarks of AD are extracellular deposits of amyloid beta (Aβ) peptides into plaques, intraneuronal accumulation of hyperphosphorylated tau protein forming tangles, and chronic inflammation. A pivotal molecule in inflammation is the pro-inflammatory cytokine TNF-α. Several lines of evidence using genetic and pharmacological manipulations indicate that TNF-α signaling exacerbates both Aβ and tau pathologies in vivo. Interestingly, preventive and intervention anti-inflammatory strategies demonstrated a reduction in brain pathology and an amelioration of cognitive function in rodent models of AD. Phase I and IIa clinical trials suggest that TNF-α inhibitors might slow down cognitive decline and improve daily activities in AD patients. In the present review, we summarize the evidence pointing towards a beneficial role of anti-TNF-α therapies to prevent or slow the progression of AD. We also present possible physical and pharmacological interventions to modulate TNF-α signaling in AD subjects along with their limitations.

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“…It has been proposed that the inflammatory response to A causes the neuronal damage in AD. Epidemiological evidence (Dziedzic et al, 2003;Sala et al, 2003) as well as experimental models of AD (Griffin and Mrak, 2002;Melton et al, 2003) show that pro-inflammatory conditions promote the development of AD. On the contrary, evidence from multiple casecontrol and population-based studies supported a roughly 50% reduction in AD risk after long-term use of non-steroidal anti-inflammatory drugs (NSAID) (Stewart et al, 1997;Broe et al, 2000;Etminan et al, 2003).…”

Section: Role Of Inflammation In Admentioning

confidence: 99%

Glial cell dysregulation: a new perspective on Alzheimer disease

2007

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Alzheimer disease (AD) is a major cause of dementia. Several mechanisms have been postulated to explain its pathogenesis, beta-amyloid (A beta toxicity, cholinergic dysfunction, Tau hyper-phosphorylation, oxidative damage, synaptic dysfunction and inflammation secondary to senile plaques, among others. Glial cells are the major producers of inflammatory mediators, and cytotoxic activation of glial cells is linked to several neurodegenerative diseases; however, whether inflammation is a consequence or the cause of neurodegeneration is still unclear. I propose that inflammation and cellular stress associated with aging are key events in the development of AD through the induction of glial dysfunction. Dysregulated inflammatory response can elicit glial cell activation by compounds which are normally poorly reactive. Inflammation can also be the major cause of defective handling of A beta and the amyloid precursor protein (APP). Here I review evidence that support the proposal that dysfunctional glia and the resulting neuroinflammation can explain many features of AD. Evidence supports the notion that damage caused by inflammation is not only a primary cause of neurodegeneration but also an inducer for the accumulation of A beta in AD. Dysfunctional glia can result in impaired neuronal function in AD, as well as in many progressive neurodegenerative disorders. We show that microglial cell activation is enhanced under pro-inflammatory conditions, indicating that glial cell responses to A beta related proteins can be critically dependent on the priming of glial cells by pro-inflammatory factors.

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Dexamethasone Inhibits TNF-α Synthesis More Effectively in Alzheimer’s Disease Patients than in Healthy Individuals

Cited by 11 publications

References 19 publications

Aging‐dependent changes of microglial cells and their relevance for neurodegenerative disorders

Aging‐dependent changes of microglial cells and their relevance for neurodegenerative disorders

Targeting Tumor Necrosis Factor Alpha for Alzheimer’s Disease

Glial cell dysregulation: a new perspective on Alzheimer disease

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