Blood pro‐inflammatory cytokines in Alzheimer's disease in relation to the use of acetylcholinesterase inhibitors

Richardson, Cassandra; Gard, Paul R.; Klugman, Anthony; Isaac, Mokhtar Gad El Kareem Nasr; Tabet, Naji

doi:10.1002/gps.3966

Cited by 17 publications

(12 citation statements)

References 37 publications

(52 reference statements)

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“…However, human studies in AD patients have not yet supported these findings; AChEI treatment was found to have no effect upon blood anti-oxidant (Klugman et al 2012) or pro-inflammatory biomarker levels after one year of treatment (Richardson et al 2013). …”

Section: Effect Of Treatmentmentioning

confidence: 93%

Slowing the progression of Alzheimer’s disease; what works?

Nelson

Tabet

2015

Ageing Research Reviews

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Section: Effect Of Treatmentmentioning

confidence: 93%

Slowing the progression of Alzheimer’s disease; what works?

Nelson

Tabet

2015

Ageing Research Reviews

Self Cite

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“…The HIV-1 coat glycoprotein gp120 has been reported to induce cellular injury and apoptosis in neurons upon sustained exposure both in vitro and in vivo , and is thought to contribute to the pathogenesis of HAND [4-9]. In addition to the surface glycoprotein CD4, gp120 also binds to the chemokine receptors CCR5 and CXCR4, which are expressed by neurons, astrocytes and microglia [7,10-12].…”

Section: Introductionmentioning

confidence: 99%

Chemokine Co-Receptor CCR5/CXCR4-Dependent Modulation of Kv2.1 Channel Confers Acute Neuroprotection to HIV-1 Glycoprotein gp120 Exposure

2013

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Infection with human immunodeficiency virus-1 (HIV-1) within the brain has long been known to be associated with neurodegeneration and neurocognitive disorder (referred as HAND), a condition characterized in its early stages by declining cognitive function and behavioral disturbances. Mechanistically, the HIV-1 coat glycoprotein 120 (gp120) has been suggested to be a critical factor inducing apoptotic cell death in neurons via the activation of p38 mitogen-activated protein kinase (MAPK), upon chronic exposure to the virus. Here we show that acute exposure of neurons to HIV-1 gp120 elicits a homeostatic response, which provides protection against non-apoptotic cell death, involving the major somatodendritic voltage-gated K+ (Kv) channel Kv2.1 as the key mediator. The Kv2.1 channel has recently been shown to provide homeostatic control of neuronal excitability under conditions of seizures, ischemia and neuromodulation/neuroinflammation. Following acute exposure to gp120, cultured rat hippocampal neurons show rapid dephosphorylation of the Kv2.1 protein, which ultimately leads to changes in specific sub-cellular localization and voltage-dependent channel activation properties of Kv2.1. Such modifications in Kv2.1 are dependent on the activation of the chemokine co-receptors CCR5 and CXCR4, and subsequent activation of the protein phosphatase calcineurin. This leads to the overall suppression of neuronal excitability and provides neurons with a homeostatic protective mechanism. Specific blockade of calcineurin and Kv2.1 channel activity led to significant enhancement of non-apoptotic neuronal death upon acute gp120 treatment. These observations shed new light on the intrinsic homeostatic mechanisms of neuronal resilience during the acute stages of neuro-HIV infections.

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“…Acetylcholinesterase inhibitors and omega-3 fatty acids have not shown significant effects on IL-6 or TNF-α levels in the blood [56,57]. Conflicting data presented in studies of cytokine levels in AD may reflect different stages of disease and possible importance of CSF cytokine studies.…”

Section: Neurobehavioral Diseasementioning

confidence: 99%

Cytokine Therapies in Neurological Disease

Azodi

Jacobson

2016

Neurotherapeutics

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Cytokines are a heterogeneous group of glycoproteins that coordinate physiological functions. Cytokine deregulation is observed in many neurological diseases. This article reviews current research focused on human clinical trials of cytokine and anticytokine therapies in the treatment of several neurological disease including stroke, neuromuscular diseases, neuroinfectious diseases, demyelinating diseases, and neurobehavioral diseases. This research suggests that cytokine therapy applications may play an important role in offering new strategies for disease modulation and treatment. Further, this research provides insights into the causal link between cytokine deregulation and neurological diseases.

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Blood pro‐inflammatory cytokines in Alzheimer's disease in relation to the use of acetylcholinesterase inhibitors

Cited by 17 publications

References 37 publications

Slowing the progression of Alzheimer’s disease; what works?

Slowing the progression of Alzheimer’s disease; what works?

Chemokine Co-Receptor CCR5/CXCR4-Dependent Modulation of Kv2.1 Channel Confers Acute Neuroprotection to HIV-1 Glycoprotein gp120 Exposure

Cytokine Therapies in Neurological Disease

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