Publications by authors named "Marta Anglada-Huguet"

In a previous study, regional reductions in cerebral glucose metabolism have been demonstrated in the tauopathy mouse model rTg4510 (Endepols et al., 2022). Notably, glucose hypometabolism was present in some brain regions without co-localized synaptic degeneration measured with [F]UCB-H.

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The stereotypical progression of Tau pathology during Alzheimer disease has been attributed to trans-neuronal spreading of misfolded Tau proteins, followed by prion-like templated aggregation of Tau. The nature of Tau and the cellular mechanisms of Tau spreading are still under debate. We hypothesized that Tau's propensity for aggregation would correlate with its ability to spread across synapses and propagate pathology.

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The accumulation of tau is a hallmark of several neurodegenerative diseases and is associated with neuronal hypoactivity and presynaptic dysfunction. Oral administration of the adenosine A receptor antagonist rolofylline (KW-3902) has previously been shown to reverse spatial memory deficits and to normalize the basic synaptic transmission in a mouse line expressing full-length pro-aggregant tau (Tau) at low levels, with late onset of disease. However, the efficacy of treatment remained to be explored for cases of more aggressive tauopathy.

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Cerebral glucose hypometabolism is a typical hallmark of Alzheimer's disease (AD), usually associated with ongoing neurodegeneration and neuronal dysfunction. However, underlying pathological processes are not fully understood and reproducibility in animal models is not well established. The aim of the present study was to investigate the regional interrelation of glucose hypometabolism measured by [F]FDG positron emission tomography (PET) with various molecular targets of AD pathophysiology using the PET tracers [F]PI-2620 for tau deposition, [F]DPA-714 for TSPO expression associated with neuroinflammation, and [F]UCB-H for synaptic density in a transgenic tauopathy mouse model.

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RTP801/REDD1 is a stress-regulated protein whose upregulation is necessary and sufficient to trigger neuronal death. Its downregulation in Parkinson's and Huntington's disease models ameliorates the pathological phenotypes. In the context of Alzheimer's disease (AD), the coding gene for RTP801, DDIT4, is responsive to Aβ and modulates its cytotoxicity in vitro.

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Background: One of the major hallmarks of Alzheimer's disease (AD)is the aberrant modification and aggregation of the microtubule-associated protein Tau . The extent of Tau pathology correlates with cognitive decline, strongly implicating Tau in the pathogenesis of the disease. Because the inhibition of Tau aggregation may be a promising therapeutic target, we tested the efficacy of BSc3094, an inhibitor of Tau aggregation, in reducing Tau pathology and ameliorating the disease symptoms in transgenic mice.

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Background: Aggregation of tau proteins is a distinct hallmark of tauopathies and has been a focus of research and clinical trials for Alzheimer's Disease. Recent reports have pointed towards a toxic effect of soluble or oligomeric tau in the spreading of tau pathology in Alzheimer's disease. Here we investigated the effects of expressing human tau repeat domain (tauRD) with pro- or anti-aggregant mutations in regulatable transgenic mouse models of Alzheimer's Disease on the functional neuronal networks and the structural connectivity strength.

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Background: The microtubule-associated protein Tau plays a role in neurodegeneration as well as neurogenesis. Previous work has shown that the expression of the pro-aggregant mutant Tau repeat domain causes strong aggregation and pronounced neuronal loss in the hippocampus whereas the anti-aggregant form has no deleterious effects. These two proteins differ mainly in their propensity to form ß structure and hence to aggregate.

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Huntington's disease (HD) is a fatal neurodegenerative disease with motor, cognitive and psychiatric impairment. Dysfunctions in HD models have been related to reduced levels of striatal brain-derived neurotrophic factor (BDNF) and imbalance between its receptors TrkB and p75(NTR). Thus, molecules with activity on the BDNF/TrkB/p75 system can have therapeutic potential.

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Accumulation of Tau is a characteristic hallmark of several neurodegenerative diseases but the mode of toxic action of Tau is poorly understood. Here, we show that the Tau protein is toxic due to its aggregation propensity, whereas phosphorylation and/or missorting is not sufficient to cause neuronal dysfunction. Aggregate-prone Tau accumulates, when expressed in vitro at near-endogenous levels, in axons as spindle-shaped grains.

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Huntington's disease (HD) is characterized by motor dysfunction due to the expression of mutant huntingtin that promotes degeneration of striatal GABAergic medium-sized spiny neurons. Here we explore the role of the 90-kDa ribosomal S6 kinase (Rsk) in the physiopathology of HD. First, we show a reduction of Rsk1 and 2 protein levels in the striatum of two HD mouse models, R6/1 and Hdh(Q7/Q111) knock-in mice, at ages when they suffer from motor disturbances.

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Huntington's disease (HD) patients and mouse models show learning and memory impairment even before the onset of motor symptoms. Deficits in hippocampal synaptic plasticity have been involved in the HD memory impairment. Several studies show that prostaglandin E2 (PGE2) EP2 receptor stimulates synaptic plasticity and memory formation.

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In this study, we evaluated the potential beneficial effects of antagonizing prostaglandin E2 (PGE2) EP1 receptor on motor and memory deficits in Huntington's disease (HD). To this aim, we implanted an osmotic mini-pump system to chronically administrate an EP1 receptor antagonist (SC-51089) in the R6/1 mouse model of HD, from 13 to 18 weeks of age, and used different paradigms to assess motor and memory function. SC-51089 administration ameliorated motor coordination and balance dysfunction in R6/1 mice as analyzed by rotarod, balance beam, and vertical pole tasks.

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The role of peroxisome proliferator activator receptor (PPAR)β/δ in the pathogenesis of Alzheimer's disease has only recently been explored through the use of PPARβ/δ agonists. Here we evaluated the effects of PPARβ/δ deficiency on the amyloidogenic pathway and tau hyperphosphorylation. PPARβ/δ-null mice showed cognitive impairment in the object recognition task, accompanied by enhanced DNA-binding activity of NF-κB in the cortex and increased expression of IL-6.

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The transcription factor Elk-1 has been revealed as neuroprotective against toxic stimuli. In this study, we explored the neuroprotective capacity of Elk-1 in Huntington's disease. To this aim, we used two exon-1 mutant huntingtin (mhtt) mouse models (R6/1 and R6/2), and a full-length mhtt striatal cell model (STHdh(Q111/Q111) ).

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Background: The 90-kDa ribosomal S6 kinase (Rsk) family is involved in cell survival. Rsk activation is regulated by sequential phosphorylations controlled by extracellular signal-regulated kinase (ERK) 1/2 and 3-phosphoinositide-dependent protein kinase 1 (PDK1). Altered ERK1/2 and PDK1 phosphorylation have been described in Huntington's disease (HD), characterized by the expression of mutant huntingtin (mhtt) and striatal degeneration.

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