A5103977715- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Nuclear Receptors and Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Breast Cancer Treatment Studies
- Cellular transport and secretion
- Metabolism and Genetic Disorders
- Intracerebral and Subarachnoid Hemorrhage Research
- Mitochondrial Function and Pathology
- Cell death mechanisms and regulation
- MicroRNA in disease regulation
- Cancer Treatment and Pharmacology
- Microbial metabolism and enzyme function
- DNA and Nucleic Acid Chemistry
- RNA regulation and disease
- Advanced Breast Cancer Therapies
- Fungal Plant Pathogen Control
- Retinal Development and Disorders
- Breast Lesions and Carcinomas
- HER2/EGFR in Cancer Research
- Lymphoma Diagnosis and Treatment
- Mesenchymal stem cell research
- Retinoids in leukemia and cellular processes
- Macrophage Migration Inhibitory Factor
- HIV/AIDS drug development and treatment
Universitat Autònoma de Barcelona
2012-2024
Biomedical Research Networking Center on Neurodegenerative Diseases
2012-2024
Universidade da Coruña
2019
Stanford University
1989-2013
Centro de Investigación Biomédica en Red
2011
City Of Hope National Medical Center
1997-2002
Disturbance of calcium homeostasis and accumulation misfolded proteins in the endoplasmic reticulum (ER) are considered contributory components cell death after ischemia. However, signal-transducing events that activated by ER stress cerebral ischemia incompletely understood. In this study, we show caspase-12 PERK IRE pathways following oxygen-glucose deprivation (OGD) mixed cortical cultures or neonatal hypoxia–ischemia (HI). Activation led to a transient phosphorylation eIF2α, an increase...
Several evidences suggest that failure of synaptic function occurs at preclinical stages Alzheimer's disease (AD) preceding neuronal loss and the classical AD pathological hallmarks. Nowadays, there is an urgent need to identify reliable biomarkers could be obtained with non-invasive methods improve diagnosis early stages. Here, we have examined plasma levels a group miRNAs related proteins in cohort composed cognitive healthy controls (HC), mild impairment (MCI) subjects.Plasma brain were...
Activity-dependent gene expression mediating changes of synaptic efficacy is important for memory storage, but the mechanisms underlying transcriptional in age-related disorders are poorly understood. In this study, we report that transcription mediated by cAMP-response element binding protein (CREB)-regulated coactivator CRTC1 impaired neurons and brain from an Alzheimer9s disease (AD) transgenic mouse expressing human β-amyloid precursor (APP<sub>Sw,Ind</sub>). Suppression CRTC1-dependent...
β-Amyloid (Aβ), a peptide generated from the amyloid precursor protein, is widely believed to underlie pathophysiology of Alzheimer disease (AD). Emerging evidences suggest that soluble Aβ oligomers adversely affect synaptic function, leading cognitive failure associated with AD. The Aβ-induced dysfunction has been attributed removal α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (AMPARs). However, molecular mechanisms underlying loss AMPAR induced by at synapses are...
Dysfunction of the vascular system contributes to brain damage and neurodegeneration, cerebral amyloid angiopathy (CAA) can be identified in a high percentage Alzheimer disease (AD) brains. Blood-brain barrier (BBB) alterations affect communication signalling between neurovascular unit (NVU) components through changes release angioneurins, among others. The two-hit hypothesis AD suggests that chronic risk factors cause an early microvasculature (hit 1) triggering cascade events leads...
PURPOSE To examine the predictive value of tumor- and treatment-specific prognostic indicators relapse-free survival (RFS) overall (OS) in patients with high-risk breast cancer (HRBC) treated high-dose chemotherapy (HDCT) stem-cell rescue. PATIENTS AND METHODS Between June 1989 September 1994, 114 HRBC (stage II > or = 10 axillary lymph nodes involved, stage IIIA, IIIB inflammatory carcinoma) received adjuvant followed by HDCT etoposide, cyclophosphamide, either doxorubicin (CAVP)...
The regulation of AMPA-type receptor (AMPAR) abundance in the postsynaptic membrane is an important mechanism involved learning and memory formation. Recent data suggest that one constituents AMPAR complex carnitine palmitoyltransferase 1C (CPT1C), a brain-specific isoform located endoplasmic reticulum neurons. Previous results had demonstrated CPT1C deficiency disrupted spine maturation hippocampal neurons impaired spatial learning, but role physiology remained mostly unknown. In present...
Journal Article Cross-Resistance to the Lipid-Soluble Antifolate Trimetrexate in Human Carcinoma Cells With Multidrug-Resistant Phenotype Get access Yehuda G. Assaraf, Assaraf Search for other works by this author on: Oxford Academic PubMed Google Scholar Arturo Molina, Molina Robert T. Schimke * *Correspondence to:Dr. Schimke, Department of Biological sciences, Stanford University, Stanford, CA 94305. JNCI: National Cancer Institute, Volume 81, Issue 4, 15 February 1989, Pages 290–294,...
We describe the development of resistance to trimetrexate and piritrexim (BW 301U) by a stepwise selection protocol in Chinese hamster ovary cells. Selection resulted initial as result dihydrofolate reductase gene amplification. Several trimetrexate-resistant variants that display 250-340-fold 25-50-fold lipophilic hydrophilic antifolates, respectively, were established. Increased antifolate was associated with prominent overexpression determined from elevated folate activity, cellular...
Bone morphogenetic proteins (BMPs) have been implicated in the generation and postnatal differentiation of cerebellar granule cells (CGCs). Here, we examined eventual role BMPs on survival these neurons. Lack depolarization causes CGC death by apoptosis vivo, a phenomenon that is mimicked vitro deprivation high potassium cultured CGCs. We found BMP-6, but not BMP-7, able to block low potassium–mediated The neuroprotective effect BMP-6 accompanied an increase Smad translocation nucleus,...
Carnitine palmitoyltransferase 1C (CPT1C) is a sensor of malonyl-CoA and located in the ER neurons. AMPA receptors (AMPARs) mediate fast excitatory neurotransmission brain play key role synaptic plasticity. In present study, we demonstrate across different metabolic stress conditions that modulate levels cortical neurons CPT1C regulates trafficking major AMPAR subunit, GluA1, through phosphatidyl-inositol-4-phosphate (PI(4)P) phosphatase SAC1. normal conditions, down-regulates SAC1 catalytic...
We report on a predictive model of long-term outcome in 114 high-risk breast cancer patients treated with high-dose chemotherapy between 1989 and 1994. Paraffin-blocks from 90 the primaries were assessed for presence five risk factors: grade, mitotic index, protein expression p53, HER2/neu, oestrogen/progesterone receptor status; we could analyse effect factors 84 these tumours. Seven-year relapse-free overall survival was 58% (95% confidence interval 44-74%) 82% 71-94%) vs 33% 21-52%) 41%...
Transcription factors have a pivotal role in synaptic plasticity and the associated modification of neuronal networks required for memory formation consolidation. The nuclear receptors subfamily 4 group A (Nr4a) emerged as possible modulators hippocampal cognitive functions. However, molecular cellular mechanisms underlying Nr4a2-mediated are not completely known. Here, we report that activity enhances Nr4a2 expression function cultured mouse neurons (both sexes) by an ionotropic glutamate...
X-linked Inhibitor of apoptosis protein (XIAP) has been classically identified as a cell death regulator. Here, we demonstrate novel function XIAP regulator neurite outgrowth in neuronal cells. In PC12 cells, overexpression prevents NGF-induced differentiation, whereas NGF treatment induces reduction endogenous levels concomitant with the induction differentiation. Accordingly, downregulation strongly increases cells well axonal and dendritic length primary cortical neurons. The effects are...
Abstract The number and function of synaptic AMPA receptors (AMPARs) tightly regulates excitatory transmission. Current evidence suggests that AMPARs are inserted into the postsynaptic membrane during long-term potentiation (LTP) removed from depression (LTD). Dephosphorylation GluA1 at Ser-845 enhanced endocytosis critical events in modulation LTD. Moreover, changes scaffold proteins density (PSD) could be also related to AMPAR regulation In present study we analyzed effect chemical LTD...
Neuronal activity promotes the survival of cerebellar granule neurons (CGNs) during postnatal development cerebellum. CGNs that fail to receive excitatory inputs will die by apoptosis. This process could be mimicked in culture exposing either a physiological concentration KCl (5 mm or K5) plus N-methyl-d-aspartate (NMDA) 25 (K25). We have previously described 24-h exposure NMDA (100 μm) K25 at 2 days vitro induced long term K5 conditions. Here we studied molecular mechanisms activated these...
ABSTRACT Alzheimer’s disease AD is associated with disruptions in neuronal communication, especially brain regions crucial for learning and memory, such as the hippocampus. The amyloid hypothesis suggests that accumulation of amyloid-beta oligomers (oAβ) contributes to synaptic dysfunction by internalisation AMPA receptors. Recently, it has been reported Nr4a2, a member Nr4a family orphan nuclear receptors, plays role hippocampal plasticity regulating BDNF Here, we demonstrate oAβ inhibits...
Cerebrovascular system dysfunctions play an active role in the onset and progression of Alzheimer's disease (AD). AD is a complex multifactorial disorder affecting several systems, which accumulation beta amyloid peptide (Aβ) one its main hallmarks. Aβ deposited around vessels brain, process known as cerebral angiopathy (CAA), it contributes to vascular activation degeneration producing reactive oxygen species inducing inflammation. These molecular processes can be also induced by excessive...