Sofia Duque Santos

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Brain injury caused by ischemia is a major cause of human mortality and physical/cognitive disability worldwide. Experimentally, brain ischemia can be induced surgically by permanent middle cerebral artery occlusion. Using this model, we studied the influence of transthyretin in ischemic stroke. Transthyretin (TTR) is normally responsible for the transport(More)
Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disease that selectively affects the peripheral nervous system. The putative cause of this life threatening pathology is tissue deposition of mutant transthyretin (TTR), initially as non-fibrillar deposits and later as fibrillar material. The mouse models currently available do not(More)
The hallmark of familial amyloid polyneuropathy (FAP) is the presence of extracellular deposits of transthyretin (TTR) aggregates and amyloid fibers in several tissues, particularly in the peripheral nervous system. The molecular pathways to neurodegeneration in FAP still remain elusive; activation of nuclear factor kappaB, pro-inflammatory cytokines,(More)
High levels of serum unconjugated bilirubin (UCB) in newborns are associated with axonal damage and glial reactivity that may contribute to subsequent neurologic injury and encephalopathy (kernicterus). Impairments in myelination and white matter damage were observed at autopsy in kernicteric infants. We have recently reported that UCB reduces(More)
The small heat shock protein αB-crystallin (HspB5) is known to be overexpressed in several neurodegenerative disorders. In familial amyloidotic polyneuropathy (FAP), a neurodegenerative disorder characterized by extracellular deposition of mutated transthyretin (TTR), activation of heat shock factor 1 -HSF1- by extracellular TTR deposition has been shown as(More)
Neurogenesis in the subventricular zone (SVZ) is regulated by diffusible factors and cell-cell contacts. In vivo, SVZ stem cells are associated with the abluminal surface of blood vessels and such interactions are thought to regulate their neurogenic capacity. SVZ neural stem cells (NSCs) have been described to contact endothelial-derived laminin via α6β1(More)
The heat shock proteins (Hsps) have been implicated in a variety of neurodegenerative diseases in which the underlying pathology is protein aggregation. Here, we studied the heat shock response in familial amyloidotic polyneuropathy (FAP), a neurodegenerative disease caused by aggregation and extracellular tissue deposition of mutated transthyretin (TTR).(More)
Over the last decades, gene therapy has emerged as a pioneering therapeutic approach to treat or prevent several diseases. Among the explored strategies, the short-term silencing of protein coding genes mediated by siRNAs has a good therapeutic potential in a clinical setting. However, the widespread use of siRNA will require the development of clinically(More)
Transthyretin (TTR) has been regarded as a neuroprotective protein given that TTR knockout (KO) mice display increased susceptibility for amyloid beta deposition and memory deficits during aging. In parallel, TTR KO mice have increased levels of neuropeptide Y (NPY), which promotes neuroprotection and neuroproliferation. In this work, we aimed at evaluating(More)
The Rho GTPase Rac1 is a multifunctional protein involved in distinct pathways ranging from development to pathology. The aim of the present study was to unravel the contribution of neuronal Rac1 in regulating the response to brain injury induced by permanent focal cerebral ischemia (pMCAO). Our results show that pMCAO significantly increased total Rac1(More)