Alzheimer’s Disease, Astrocytes and Kynurenines

Dézsi, Lívia; Tuka, Bernadett; Martos, Diána; Vécsei, László

doi:10.2174/156720501205150526114000

Cited by 29 publications

(23 citation statements)

References 1 publication

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“…Astrocytes, earlier presumed to serve as supportive roles for the neuronal network, have recently been shown to play an active role in the synaptic dysfunction, impairment of homeostasis, inflammation, as well as excitotoxicity in relation to several neurological disorders (Dezsi et al, 2015). The role of astrocytes in the neuroprotective effects of agathisflavone against glutamate-induced excitotoxicity was evaluated.…”

Section: Discussionmentioning

confidence: 99%

Agathisflavone, a flavonoid derived from Poincianella pyramidalis (Tul.), enhances neuronal population and protects against glutamate excitotoxicity

et al. 2018

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Flavonoids are bioactive compounds that are known to be neuroprotective against glutamate-mediated excitotoxicity, one of the major causes of neurodegeneration. The mechanisms underlying these effects are unresolved, but recent evidence indicates flavonoids may modulate estrogen signaling, which can delay the onset and ameliorate the severity of neurodegenerative disorders. Furthermore, the roles played by glial cells in the neuroprotective effects of flavonoids are poorly understood. The aim of this study was to investigate the effects of the flavonoid agathisflavone (FAB) in primary neuron-glial co-cultures from postnatal rat cerebral cortex. Compared to controls, treatment with FAB significantly increased the number of neuronal progenitors and mature neurons, without increasing astrocytes or microglia. These pro-neuronal effects of FAB were suppressed by antagonists of estrogen receptors (ERα and ERβ). In addition, treatment with FAB significantly reduced cell death induced by glutamate and this was associated with reduced expression levels of pro-inflammatory (M1) microglial cytokines, including TNFα, IL1β and IL6, which are associated with neurotoxicity, and increased expression of IL10 and Arginase 1, which are associated with anti-inflammatory (M2) neuroprotective microglia. We also observed that FAB increased neuroprotective trophic factors, such as BDNF, NGF, NT4 and GDNF. The neuroprotective effects of FAB were also associated with increased expression of glutamate regulatory proteins in astrocytes, namely glutamine synthetase (GS) and Excitatory Amino Acid Transporter 1 (EAAT1). These findings indicate that FAB acting via estrogen signaling stimulates production of neurons in vitro and enhances the neuroprotective properties of microglia and astrocytes to significantly ameliorate glutamate-mediated neurotoxicity.

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Section: Discussionmentioning

confidence: 99%

Agathisflavone, a flavonoid derived from Poincianella pyramidalis (Tul.), enhances neuronal population and protects against glutamate excitotoxicity

et al. 2018

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“…In the pathology of different neurodegenerative disorders, the metabolism of endogenous TRY to kynurenic acid (KYNA) and/or quinolinic acid (QUIN) has received intensified attention because of its dual behavior of being neuroprotective or neurotoxic [71,72,73,74,75,76,77,78]. The steps of TRY metabolism are shown in Figure 1.…”

Section: Excitotoxicity In Multiple Sclerosismentioning

confidence: 99%

“…The fundamental and general participation of Glu in ODC death, axon damage, and BBB-dysfunction provides a promising target. Glutamate excitotoxicity is a common pathological reaction for different noxa attacking CNS cells [5], so experimental drugs hold hope for treating not only MS but other severe neurodegenerative disorders like ALS, Alzheimer’s or stroke [73,75,77,78]. In EAE, a great variety of drugs connected to Glu metabolism have been tested.…”

Section: Therapeutic Trialsmentioning

confidence: 99%

Excitotoxins, Mitochondrial and Redox Disturbances in Multiple Sclerosis

Rajda

Pukoli

Bende

et al. 2017

IJMS

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Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). There is increasing evidence that MS is not only characterized by immune mediated inflammatory reactions, but also by neurodegenerative processes. There is cumulating evidence that neurodegenerative processes, for example mitochondrial dysfunction, oxidative stress, and glutamate (Glu) excitotoxicity, seem to play an important role in the pathogenesis of MS. The alteration of mitochondrial homeostasis leads to the formation of excitotoxins and redox disturbances. Mitochondrial dysfunction (energy disposal failure, apoptosis, etc.), redox disturbances (oxidative stress and enhanced reactive oxygen and nitrogen species production), and excitotoxicity (Glu mediated toxicity) may play an important role in the progression of the disease, causing axonal and neuronal damage. This review focuses on the mechanisms of mitochondrial dysfunction (including mitochondrial DNA (mtDNA) defects and mitochondrial structural/functional changes), oxidative stress (including reactive oxygen and nitric species), and excitotoxicity that are involved in MS and also discusses the potential targets and tools for therapeutic approaches in the future.

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“…Alzheimer's disease (AD), a severe age-related neurodegenerative disorder, is characterized by the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles, synaptic and neuronal loss, and cognitive decline (1,2). An estimated 5.3 million Americans have AD; 5.1 million of these are aged 65 and over, and approximately 200,000 are <65 years-of-age and have younger onset AD (3).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-135b has a neuroprotective role via targeting of β-site APP-cleaving enzyme 1

Zhang

Xing

Guo

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. MicroRNAs (miRs) are a class of endogenous small non-coding RNAs that have been revealed to negatively mediate the expression of their target genes at the post-transcriptional level. Recently, particular miRs have demonstrated an involvement in the pathogenesis of Alzheimer's disease (AD). However, the specific role of miR-135b in AD has yet to be elucidated. The present study aimed to investigate the neuroprotective role of miR-135b, in addition to its underlying mechanism. Herein, reverse transcription-quantitative polymerase chain reaction was conducted to determine miR-135b expression levels in the peripheral blood samples of patients with AD and age-matched normal controls. The data of the present study revealed that the expression levels of miR-135b were significantly reduced in the peripheral blood of AD patients compared with normal controls (P<0.01). In vitro MTT analyses identified that the overexpression of miR-135b significantly enhanced the proliferation of hippocampal cells (P<0.01). Furthermore, in vivo analysis using a Y-maze test indicated that injection with miR-135b mimics into the third ventricle of anesthetized SAMP8 mice significantly enhanced their learning and memory capacities (P<0.01). Molecular mechanism investigations identified β-site APP-cleaving enzyme 1 (BACE1) as a direct target gene of miR-135b, and the latter was identified to negatively mediate the protein expression levels of BACE1 in hippocampal cells, in addition to hippocampal tissues, of SAMP8 mice. Based on the aforementioned findings, we propose that miR-135b has a neuroprotective role via direct targeting of BACE1 and, thus, may be used for the treatment of AD.

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Alzheimer’s Disease, Astrocytes and Kynurenines

Cited by 29 publications

References 1 publication

Agathisflavone, a flavonoid derived from Poincianella pyramidalis (Tul.), enhances neuronal population and protects against glutamate excitotoxicity

Agathisflavone, a flavonoid derived from Poincianella pyramidalis (Tul.), enhances neuronal population and protects against glutamate excitotoxicity

Excitotoxins, Mitochondrial and Redox Disturbances in Multiple Sclerosis

MicroRNA-135b has a neuroprotective role via targeting of β-site APP-cleaving enzyme 1

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