Neuroprotective effects of the Alzheimer's disease-related gene seladin-1

Peri, Alessandro; Serio, Mario

doi:10.1677/jme-08-0071

Cited by 62 publications

(41 citation statements)

References 80 publications

(76 reference statements)

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“…24 In brain and other tissues, several authors have described the implication of seladin-1/DHCR24 in different processes like apoptosis, inflammation, oxidative stress, and neurodegeneration. 1,3,5,8,25 We hereby demonstrate for the first time the protective role of seladin-1/DHCR24 against experimental stroke induced by MCAO in mice.…”

Section: Discussionmentioning

confidence: 99%

Seladin-1/DHCR24 Is Neuroprotective by Associating EAAT2 Glutamate Transporter to Lipid Rafts in Experimental Stroke

Hernández-Jiménez

Martínez-López

Gabandé‐Rodríguez

et al. 2016

Stroke

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Background and Purpose-3β-Hydroxysteroid-Δ24 reductase (DHCR24) or selective alzheimer disease indicator 1 (seladin-1), an enzyme of cholesterol biosynthetic pathway, has been implicated in neuroprotection, oxidative stress, and inflammation. However, its role in ischemic stroke remains unexplored. The aim of this study was to characterize the effect of seladin-1/DHCR24 using an experimental stroke model in mice. Methods-Dhcr24+/− and wild-type (WT) mice were subjected to permanent middle cerebral artery occlusion. In another set of experiments, WT mice were treated intraperitoneally either with vehicle or U18666A (seladin-1/DHCR24 inhibitor, 10 mg/kg) 30 minutes after middle cerebral artery occlusion. Brains were removed 48 h after middle cerebral artery occlusion for infarct volume determination. For protein expression determination, peri-infarct region was obtained 24 h after ischemia, and Western blot or cytometric bead array was performed. Results-Dhcr24+/− mice displayed larger infarct volumes after middle cerebral artery occlusion than their WT littermates. Treatment of WT mice with the seladin-1/DHCR24 inhibitor U18666A also increased ischemic lesion. Inflammationrelated mediators were increased after ischemia in Dhcr24 +/− mice compared with WT counterparts. Consistent with a role of cholesterol in proper function of glutamate transporter EAAT2 in membrane lipid rafts, we found a decreased association of EAAT2 with lipid rafts after ischemia when DHCR24 is genetically deleted or pharmacologically inhibited. Accordingly, treatment with U18666A decreases

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Section: Discussionmentioning

confidence: 99%

Seladin-1/DHCR24 Is Neuroprotective by Associating EAAT2 Glutamate Transporter to Lipid Rafts in Experimental Stroke

Hernández-Jiménez

Martínez-López

Gabandé‐Rodríguez

et al. 2016

Stroke

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“…The hallmarks of AD include the amyloid plaques generated from amyloid β (Aβ) peptide and the neur o f i b r i l l a r y t a n g l e s w h i c h a r e a g g r e g a t e s o f hyperphosphorylated tau protein. In addition, AD has been associated with upregulated neuroinflammation and oxidative stress with consequent neuronal loss in distinct brain areas including the neocortex and hippocampus [1][2][3][4][5]. Aberrations of brain neurotransmitter levels including acetylcholine, a key player in AD progression, besides dopamine, GABA, and glutamate have been implicated in AD pathogenesis [1,6,7].…”

Section: Introductionmentioning

confidence: 99%

Bone Marrow-Derived Endothelial Progenitor Cells Protect Against Scopolamine-Induced Alzheimer-Like Pathological Aberrations

et al. 2014

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Vascular endothelial dysfunction plays a key role in the pathogenesis of Alzheimer's disease (AD). Patients with AD have displayed decreased circulating endothelial progenitor cells (EPCs) which repair and maintain the endothelial function. Transplantation of EPCs has emerged as a promising approach for the management of cerebrovascular diseases including ischemic stroke, however, its impact on AD has been poorly described. Thus, the current study aimed at investigating the effects of bone marrow-derived (BM) EPCs transplantation in repeated scopolamine-induced cognitive impairment, an experimental model that replicates biomarkers of AD. Intravenously transplanted BM-EPCs migrated into the brain of rats and improved the learning and memory deficits. Meanwhile, they mitigated the deposition of amyloid plaques and associated histopathological alterations. At the molecular levels, BM-EPCs blunted the increase of hippocampal amyloid beta protein (Aβ), amyloid precursor protein (APP) and reinstated the Aβ-degrading neprilysin together with downregulation of p-tau and its upstream glycogen synthase kinase-3β (GSK-3β). They also corrected the perturbations of neurotransmitter levels including restoration of acetylcholine and associated esterase along with dopamine, GABA, and the neuroexitatory glutamate. Furthermore, BM-EPCs induced behavioral recovery via boosting of vascular endothelial growth factor (VEGF), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and its upstream cAMP response element binding (CREB), suppression of the proinflammatory tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and upregulation of interleukin-10 (IL-10). BM-EPCs also augmented Nrf2 and seladin-1. Generally, these actions were analogous to those exerted by adipose tissue-derived mesenchymal stem cells (AT-MSCs) and the reference anti-Alzheimer donepezil. For the first time, these findings highlight the beneficial actions of BM-EPCs against the memory deficits and AD-like pathological dysfunction.

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“…In neoplastic tissues and cell lines, its expression varies and both down-and up-regulation have been reported, compared with the corresponding normal counterparts. A high expression level has been observed in prostate [29,30], liver, lung [20], ovarian cancer [25], and metastatic melanoma [28], and in cell lines derived from cerebral tumours and from neuroblastoma [26]. Conversely, seladin-1 is down-regulated in adrenal cancer compared with adenoma and normal adrenal tissue [23].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, seladin-1 is expressed in the brain and in various endocrine organs, such as adrenal cortex [21][22][23][24], testis, and ovary [20,22,25]. Seladin-1 effectively inhibits caspase-3 activity, a key mediator of apoptosis, and protects neuronal cells from apoptotic death [20,26,27], thus suggesting its involvement in the regulation of cell survival and death.…”

Section: Introductionmentioning

confidence: 99%

Seladin‐1 and testicular germ cell tumours: new insights into cisplatin responsiveness

Nuti

Luciani

Marinari

et al. 2009

The Journal of Pathology

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The molecular basis for the exquisite sensitivity of testicular germ cell tumours of adolescents and adults (TGCTs), ie seminomas and non-seminomatous germ cell tumours, to chemo/radiotherapy has not been fully clarified so far. It has been suggested that it may be dependent on factors involved in the regulation of apoptosis. Seladin-1 is a multi-functional protein involved in various biological processes, including apoptosis. The aim of our study was to assess the expression of seladin-1 in different histological types of TGCTs, known to have varying treatment sensitivity, in order to establish whether this protein may influence cisplatin responsiveness in vitro. Seladin-1 expression levels, both at the mRNA and at the protein level, were higher in the adjacent normal parenchyma than in the pathological counterparts. In tumoural tissues, the level of expression differed among TGCT histological types. The highest tumour-expression level was found in teratoma, whereas the lowest was detected in seminoma, corresponding to the different chemo/and radiosensitivities of these tumour types. In common with other cancers, in TGCT-derived cell lines seladin-1 showed anti-apoptotic properties through inhibition of caspase-3 activation. We confirmed our results using a non-seminomatous cell line model (NT2) before and after differentiation with retinoic acid. Significantly higher seladin-1 expression was observed in the differentiated derivatives (teratoma) and an inverse relationship was found between seladin-1 expression and the amount of cleaved caspase-3. Seladin-1 silencing or overexpression in this cell line supports involvement of seladin-1 in cisplatin responsiveness. Seladin-1 silencing was associated with greater cisplatin responsiveness demonstrated by decreased cell viability and increased expression of apoptotic markers. In contrast, overexpression of seladin-1 was associated with a higher survival rate and a clear anti-apoptotic effect. In conclusion, we have demonstrated for the first time an important role for seladin-1 in the biology of TGCTs and provided new insights into cisplatin responsiveness of these tumours.

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Neuroprotective effects of the Alzheimer's disease-related gene seladin-1

Cited by 62 publications

References 80 publications

Seladin-1/DHCR24 Is Neuroprotective by Associating EAAT2 Glutamate Transporter to Lipid Rafts in Experimental Stroke

Seladin-1/DHCR24 Is Neuroprotective by Associating EAAT2 Glutamate Transporter to Lipid Rafts in Experimental Stroke

Bone Marrow-Derived Endothelial Progenitor Cells Protect Against Scopolamine-Induced Alzheimer-Like Pathological Aberrations

Seladin‐1 and testicular germ cell tumours: new insights into cisplatin responsiveness

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