Suppression of Glial HO-1 Activitiy as a Potential Neurotherapeutic Intervention in AD

Schipper, Hyman M.; Gupta, Ajay; Szarek, Walter A.

doi:10.2174/156720509789207985

Cited by 55 publications

(47 citation statements)

References 67 publications

(90 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The neuritic damage, aberrant DA and 5-HT levels, and behavioral disturbances observed in GFAP.HMOX1 mice constitute direct evidence that profound neurochemical and neurodystrophic effects may be evoked by a primary insult to the astroglial compartment. This formulation is consistent with recent perception of astroglia as (1) a full partner, along with presynaptic and postsynaptic neurons, in the "tripartite synapse" (Perea et al, 2009) providing essential contributions to Ca 2ϩ signaling networks, synaptogenesis, synaptic transmission, and gliotransmission (Haydon and Carmignoto, 2006); (2) a driver of neurological dysfunction as in the case of hyperammonemic encephalopathy (Brusilow et al, 2010), blood-brain barrier disruption (Krum, 1994), and chronic neuropathic pain syndromes (Hulsebosch, 2008); and (3) a legitimate target for therapeutic intervention (Schipper et al, 2009b). Involvement of ependymocytes and tanycytes in the GFAP.HMOX1 neurophenotype, albeit unlikely given the topography of the structural and biochemical lesions, cannot be entirely excluded as these cells express GFAP and the HMOX1 transgene.…”

Section: Discussionmentioning

confidence: 99%

Schizophrenia-Like Features in Transgenic Mice Overexpressing Human HO-1 in the Astrocytic Compartment

et al. 2012

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Schizophrenia-Like Features in Transgenic Mice Overexpressing Human HO-1 in the Astrocytic Compartment

et al. 2012

View full text Add to dashboard Cite

“…For example, inducible nitric oxide synthase (iNOS) is induced in astrocytes and microglia activated under brain ischemia through nuclear factor-kappaB (NF-κB) signaling pathway together with proinflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α (Nomura, 2001). Glial function is important to neuronal function and survival (Benarroch, 2005;Chadi et al, 2009;Schipper et al, 2009;Tsacopoulos et al, 1997;Varvel et al, 2009).…”

mentioning

confidence: 99%

Transglutaminase 2 expression induced by lipopolysaccharide stimulation together with NO synthase induction in cultured astrocytes

Takano

Shiraiwa

Moriyama

et al. 2010

Neurochemistry International

View full text Add to dashboard Cite

Abstract-Activation of glia has been observed in neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis and brain ischemia. Excessive production of nitric oxide (NO), as a consequence of increased inducible NO synthase (iNOS) in glia, contributes to neurodegeneration. Transglutaminase 2 (TG2) is a cross-linking enzyme, which is activated in neurodegenerative diseases such as PD, AD and Huntington's diseases. However, mechanisms contributing to the increased TG activity in neurodegenerative diseases remain to be clarified. In the present study, we examined the expression of TG2 in cultured rat hippocampal astrocytes activated with lipopolysaccharide (LPS), which is generally used for a stimulant of iNOS induction. The expressions of TG2 mRNA and protein were increased by stimulation with LPS in a dose-dependent manner. The LPS-induced TG2 expression was diminished by ammonium pyrrolidine-1-carbodithioate; an inhibitor for nuclear factor (NF)-κB activation, suggesting the factors involved. Both expressions of TG2 and iNOS induced by LPS stimulation were suppressed by an antioxidant, ethyl pyruvate, in a dose-dependent manner. Furthermore, they were also suppressed by cystamine, an inhibitor of TG activity. These results suggest that the level of TG2 expression is regulated by oxidative stress and the activity of TG itself, and that the induction of iNOS and NO production are closely associated with TG2 expression in LPS-stimulated activation of astrocytes.

show abstract

“…Moreover, the majority of hippocampal astrocytes (86%) in the AD brain express heme oxygenase (HO-1), while normal astrocytes almost do not express HO-1 at all (6-7%). This is indicative of oxidative stress occurring in the astrocytes during AD [74].…”

Section: Astrocytes In Alzheimer's Diseasementioning

confidence: 94%

Mitochondrial Function in Alzheimer’s Disease: Focus on Astrocytes

Lampinen¹,

Belaya²,

Boccuni³

et al. 2018

Astrocyte - Physiology and Pathology

View full text Add to dashboard Cite

The brain is one of the most energy-requiring organs in the human body. Mitochondria not only generate this energy, but are centrally involved critical cellular functions including maintenance of calcium homeostasis, synthesis of biomolecules, and cell signaling. Even though neurons and astrocytes preferentially use different energy substrates and metabolic pathways, these two cell types are intricately linked in their energy metabolism. Recently it has become clear that astrocytes have a key role in the regulation and support of the neuronal mitochondrial quality control, yet several questions remain unanswered to fully understand the mechanisms of mitochondrial function, transport, turnover and degradation in astrocytes. Alzheimer's disease is the most common neurodegenerative disorder, the exact mechanisms of which remain incompletely understood. The fact that astrocytic mitochondrial dysfunction is an early event in the pathogenesis of Alzheimer's disease suggests that more research on mitochondrial function and impairment is required in the hopes of disease alleviation in the future.

show abstract

Suppression of Glial HO-1 Activitiy as a Potential Neurotherapeutic Intervention in AD

Cited by 55 publications

References 67 publications

Schizophrenia-Like Features in Transgenic Mice Overexpressing Human HO-1 in the Astrocytic Compartment

Schizophrenia-Like Features in Transgenic Mice Overexpressing Human HO-1 in the Astrocytic Compartment

Transglutaminase 2 expression induced by lipopolysaccharide stimulation together with NO synthase induction in cultured astrocytes

Mitochondrial Function in Alzheimer’s Disease: Focus on Astrocytes

Contact Info

Product

Resources

About