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Spinal astrocyte dysfunction drives motor neuron loss in late-onset spinal muscular atrophy
AbstractSpinal muscular atrophy (SMA) is a progressive neuromuscular disorder caused by a loss of thesurvival of motor neuron 1 (SMN1) gene, resulting in a loss of spinal motor neurons (MNs), leading to muscle weakness and wasting. The pathogenesis of MN loss in SMA and the selective vulnerability in different cellular populations are not fully understood. To investigate the role of spinal astrocytes in the pathogenesis of late-onset SMA, we used a mouse model in addition to in vitro approaches. Immunostaining, Western blot analysis, small interfering ribonucleic acid (siRNA) transfections, functional assays,  enzyme-link...
Source: Acta Neuropathologica - March 17, 2023 Category: Neurology Source Type: research

HIF-1 α is involved in blood–brain barrier dysfunction and paracellular migration of bacteria in pneumococcal meningitis
AbstractBacterial meningitis is a deadly disease most commonly caused byStreptococcus pneumoniae, leading to severe neurological sequelae including cerebral edema, seizures, stroke, and mortality when untreated. Meningitis is initiated by the transfer ofS. pneumoniae from blood to the brain across the blood –cerebrospinal fluid barrier or the blood–brain barrier (BBB). The underlying mechanisms are still poorly understood. Current treatment strategies include adjuvant dexamethasone for inflammation and cerebral edema, followed by antibiotics. The success of dexamethasone is however inconclusive, ne cessitating new ther...
Source: Acta Neuropathologica - June 10, 2020 Category: Neurology Source Type: research

Genome-wide, high-content siRNA screening identifies the Alzheimer ’s genetic risk factor FERMT2 as a major modulator of APP metabolism
AbstractGenome-wide association studies (GWASs) have identified 19 susceptibility loci for Alzheimer ’s disease (AD). However, understanding how these genes are involved in the pathophysiology of AD is one of the main challenges of the “post-GWAS” era. At least 123 genes are located within the 19 susceptibility loci; hence, a conventional approach (studying the genes one by one) would not be time- and cost-effective. We therefore developed a genome-wide, high-content siRNA screening approach and used it to assess the functional impact of gene under-expression on APP metabolism. We found that 832 genes modulated APP m...
Source: Acta Neuropathologica - December 7, 2016 Category: Neurology Source Type: research

Mesenchymal stem cells enhance α-synuclein clearance via M2 microglia polarization in experimental and human parkinsonian disorder
In this study, we investigated whether mesenchymal stem cells (MSCs) enhance the phagocytic clearance of α-synuclein via M2 microglia polarization, and thereby exert neuroprotective effects in α-synuclein-enriched experimental models and patients with multiple system atrophy (MSA). Treatment of BV2 cells with α-synuclein induced an inflammatory phenotype, whereas co-culture of α-synuclein-treated B V2 cells with MSCs induced an anti-inflammatory M2 phenotype, with decreased α-synuclein levels and increased lysosomal activity, leading to greater viability of neuronal cells co-cultured with BV2 cells. Using IL-4 recepto...
Source: Acta Neuropathologica - August 5, 2016 Category: Neurology Source Type: research

PDCD10 (CCM3) regulates brain endothelial barrier integrity in cerebral cavernous malformation type 3: role of CCM3-ERK1/2-cortactin cross-talk
This study highlights the potential role of CCM3 in regulating TJ complex organization and brain endothelial barrier permeability.
Source: Acta Neuropathologica - September 18, 2015 Category: Neurology Source Type: research