Search results for "Neuroprotection"

2019

Beside diverse therapeutic properties of palmitoylethanolamide (PEA) including: neuroprotection, inflammation and pain alleviation, prophylactic effects have also been reported in animal models of infections, inflammation, and neurological diseases. The availability of PEA as (ultra)micronized nutraceutical formulations with reportedly no side effects, renders it accordingly an appealing candidate in human preventive care, such as in population at high risk of disease development or for healthy aging. PEA’s mode of action is multi-facetted. Consensus exists that PEA’s effects are primarily modulated by the peroxisome proliferator-activated receptor alpha (PPARα) and that PEA-activated PPARα…

Enhanced activity of glycolytic enzymes in Drosophila and human cell models of Parkinson's disease based on DJ-1 deficiency

2020

ABSTRACTParkinson’s disease (PD) is a neurodenerative debilitating disorder characterized by progressive disturbances in motor, autonomic and psychiatric functions. The pathological hallmark of PD is the loss of dopaminergic neurons in the substantia nigra pars compacta, which causes striatal dopamine deficiency. Although most PD cases are sporadic (iPD), approximately 5-10% of all patients suffer from monogenic PD forms caused by highly penetrant rare mutations segregating with the disease in families (fPD). One of the genes linked to monogenic PD is DJ-1. Mutations in DJ-1 cause autosomal recessive early-onset forms of fPD; however, it has been shown that an over-oxidized and inactive for…

(+)-Pentazocine reduces oxidative stress and apoptosis in microglia following hypoxia/reoxygenation injury

2016

Abstract Background Sigma-1 receptors (σ 1 R) are highly expressed in neurons as well as microglia and have been shown to modulate the inflammatory response in the central nervous system and thus may serve as possible target for neuroprotective strategies. The aim of the present study was to test the effect of (+)-pentazocine, a putative σ 1 R agonist, in an in vitro model of microglia activation. Methods Microglia (BV2 cells) was exposed (3 h) to 1% oxygen and reoxygenation was allowed for 24 h. Cells were treated with different concentrations (1, 10, 25 and 50 μM) of (+)-pentazocine in the presence or absence of NE-100 (1 μM), a well established σ 1 R antagonist. Cell viability and apopto…

Comparative Proteomics Unveils LRRFIP1 as a New Player in the DAPK1 Interactome of Neurons Exposed to Oxygen and Glucose Deprivation

2020

Altres ajuts: The group has received funding from 'la Caixa Foundation' CI15-00009, from the European Institute of Innovation and Technology (EIT) PoC-2016-SPAIN-04, which receives support from the European Union's Horizon 2020 research and innovation program, and from the 'Fundación para la Innovación y la Prospectiva en Salud en España (FIPSE)' program 3594-18. Death-associated protein kinase 1 (DAPK1) is a pleiotropic hub of a number of networked distributed intracellular processes. Among them, DAPK1 is known to interact with the excitotoxicity driver NMDA receptor (NMDAR), and in sudden pathophysiological conditions of the brain, e.g., stroke, several lines of evidence link DAPK1 with t…

Peroxisome proliferator-activated receptor-γ coactivator-1α mediates neuroprotection against excitotoxic brain injury in transgenic mice: role of mit…

2016

Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a transcriptional coactivator involved in the regulation of mitochondrial biogenesis and cell defense. The functions of PGC-1α in physiology of brain mitochondria are, however, not fully understood. To address this we have studied wild-type and transgenic mice with a two-fold overexpression of PGC-1α in brain neurons. Data showed that the relative number and basal respiration of brain mitochondria were increased in PGC-1α transgenic mice compared with wild-type mitochondria. These changes occurred concomitantly with altered levels of proteins involved in oxidative phosphorylation (OXPHOS) as studied by proteomi…

2019

Traumatic brain injury (TBI) can lead to impaired cognition and memory consolidation. The acute phase (24–48 h) after TBI is often characterized by neural dysfunction in the vicinity of the lesion, but also in remote areas like the contralateral hemisphere. Protein homeostasis is crucial for synaptic long-term plasticity including the protein degradation systems, proteasome and autophagy. Still, little is known about the acute effects of TBI on synaptic long-term plasticity and protein degradation. Thus, we investigated TBI in a controlled cortical impact (CCI) model in the motor and somatosensory cortex of mice ex vivo-in vitro. Late long-term potentiation (l-LTP) was induced by theta-burs…

The Small Heat Shock Protein α-Crystallin B Shows Neuroprotective Properties in a Glaucoma Animal Model

2017

Glaucoma is a neurodegenerative disease that leads to irreversible retinal ganglion cell (RGC) loss and is one of the main causes of blindness worldwide. The pathogenesis of glaucoma remains unclear, and novel approaches for neuroprotective treatments are urgently needed. Previous studies have revealed significant down-regulation of α-crystallin B as an initial reaction to elevated intraocular pressure (IOP), followed by a clear but delayed up-regulation, suggesting that this small heat-shock protein plays a pathophysiological role in the disease. This study analyzed the neuroprotective effect of α-crystallin B in an experimental animal model of glaucoma. Significant IOP elevation induced b…

Neuroprotective effects of physical activity via the adaptation of astrocytes

2021

The multifold benefits of regular physical exercise have been largely demonstrated in human and animal models. Several studies have reported the beneficial effects of physical activity, both in peripheral tissues and in the central nervous system (CNS). Regular exercise improves cognition, brain plasticity, neurogenesis and reduces the symptoms of neurodegenerative diseases, making timeless the principle of “mens sana in corpore sano” (i.e., a healthy mind in a healthy body). Physical exercise promotes morphological and functional changes in the brain, acting not only in neurons but also in astrocytes, which represent the most numerous glial cells in the brain. The multiple effects of exerc…

Nutraceutical Supplementation Ameliorates Visual Function, Retinal Degeneration, and Redox Status in rd10 Mice

2021

Background: Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by progressive degeneration of photoreceptor cells. Ocular redox status is altered in RP suggesting oxidative stress could contribute to their progression. In this study, we investigated the effect of a mixture of nutraceuticals with antioxidant properties (NUT) on retinal degeneration in rd10 mice, a model of RP. Methods: NUT was orally administered to rd10 mice from postnatal day (PD) 9 to PD18. At PD18 retinal function and morphology were examined by electroretinography (ERG) and histology including TUNEL assay, immunolabeling of microglia, Müller cells, and poly ADP ribose polymers. Retinal r…

Molecular chaperones in the brain endothelial barrier: neurotoxicity or neuroprotection?

2019

Brain microvascular endothelial cells (BMECs) interact with astrocytes and pericytes to form the blood-brain barrier (BBB). Their compromised function alters the BBB integrity, which is associated with early events in the pathogenesis of cancer, neurodegenerative diseases, and epilepsy. Interestingly, these conditions also induce the expression of heat shock proteins (HSPs). Here we review the contribution of major HSP families to BMEC and BBB function. Although investigators mainly report protective effects of HSPs in brain, contrasted results were obtained in BMEC, which depend both on the HSP and on its location, intra- or extracellular. The therapeutic potential of HSPs must be scrupulo…