A5038298684- Alzheimer's disease research and treatments
- Wnt/β-catenin signaling in development and cancer
- Nuclear Receptors and Signaling
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- RNA regulation and disease
- Extracellular vesicles in disease
- Neurological disorders and treatments
- Sirtuins and Resveratrol in Medicine
- Genetics and Neurodevelopmental Disorders
- RNA Interference and Gene Delivery
- Cellular transport and secretion
- CRISPR and Genetic Engineering
- Autism Spectrum Disorder Research
- Protein Kinase Regulation and GTPase Signaling
- Ubiquitin and proteasome pathways
- Muscle Physiology and Disorders
- Heat shock proteins research
- Signaling Pathways in Disease
- Adipose Tissue and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Trace Elements in Health
- Calpain Protease Function and Regulation
University College London
2020-2024
Departament de Salut
2021-2023
Universitat de Barcelona
2014-2023
Cardiff University
2023
UK Dementia Research Institute
2023
Biomedical Research Networking Center on Neurodegenerative Diseases
2023
Extracellular vesicles (EVs) play an important role in intercellular communication as carriers of signalling molecules such bioactive miRNAs, proteins and lipids. EVs are key players the functioning central nervous system (CNS) by influencing synaptic events modulating recipient neurons. However, specific neuron-to-neuron via is still not well understood. Here, we provide evidence that primary neurons uptake neuron-derived soma, dendrites, even dendritic spines, carry proteins....
Synapse loss strongly correlates with cognitive decline in Alzheimer's disease (AD), but the underlying mechanisms are poorly understood. Deficient Wnt signaling contributes to synapse dysfunction and AD. Consistently, a variant of LRP6 receptor, (LRP6-Val), reduced signaling, is linked late-onset However, impact LRP6-Val on healthy AD brain has not been examined. Knock-in mice, generated by gene editing, carrying this Lrp6 develop normally. neurons from Lrp6-val mice do respond Wnt7a,...
Growing evidence supports a role for deficient Wnt signalling in Alzheimer's disease (AD). First, the antagonist DKK1 is elevated AD brains and required amyloid-β-induced synapse loss. Second, LRP6 co-receptor integrity three variants of this receptor are linked to late-onset AD. However, expression/role other components remain poorly explored receptors Frizzled1 (Fzd1), Fzd5, Fzd7 Fzd9 interest due their formation/plasticity. Our analyses showed reduced FZD1 FZD7 mRNA levels hippocampus...
Increasing evidence supports a role for deficient Wnt signaling in Alzheimer’s disease (AD). Studies reveal that the secreted antagonist Dickkopf-3 (DKK3) colocalizes to amyloid plaques AD patients. Here, we investigate contribution of DKK3 synapse integrity healthy and brains. Our findings show expression is upregulated brains subjects protein levels increase at early stages disease. In hAPP-J20 hAPP NL-G-F/NL-G-F mouse models, extracellular are increased accumulates dystrophic neuronal...
Abstract Mutations in the PARK2 gene are associated with an autosomal recessive form of juvenile parkinsonism (AR-JP). These mutations affect parkin solubility and impair its E3 ligase activity, leading to a toxic accumulation proteins within susceptible neurons that results slow but progressive neuronal degeneration cell death. Here, we report RTP801/REDD1, pro-apoptotic negative regulator survival kinases mTOR Akt, is one such substrates. We observed knockdown elevated RTP801 sympathetic...
Parkinson's disease (PD) is a disorder characterized by the degeneration of certain neuronal populations in central and peripheral nervous system. One hallmarks toxic accumulation proteins within susceptible neurons due to major impairment degradation/clearance protein systems.RTP801 pro-apoptotic that sufficient necessary induce death cellular animal models PD. RTP801 also upregulated sporadic parkin mutant PD brains. Here, we report role NEDD4, an E3 ligase involved α-synuclein degradation...
Single nucleotide polymorphisms (SNPs) in the α-synuclein (SNCA) gene are associated with differential risk and age at onset (AAO) of both idiopathic Leucine-rich repeat kinase 2 (LRRK2)-associated Parkinson's disease (PD). Yet potential combinatory or synergistic effects among several modulatory SNPs for PD AAO remain largely underexplored.The mechanistic target rapamycin (mTOR) signaling pathway is functionally impaired PD. Here we explored whether mTOR pathway, alone by epistatic...
Abstract RTP801/REDD1 is a stress-responsive protein that mediates mutant huntingtin (mhtt) toxicity in cellular models and up regulated Huntington’s disease (HD) patients’ putamen. Here, we investigated whether RTP801 involved motor impairment HD by affecting striatal synaptic plasticity. To explore this hypothesis, ectopic mhtt was over expressed cultured rat primary neurons. Moreover, the levels of were assessed homogenates crude fractions from human postmortem brains mouse HD. Finally,...
Structural plasticity of synapses correlates with changes in synaptic strength. Dynamic modifications dendritic spine number and size are crucial for long-term potentiation (LTP), the cellular correlate learning memory. Recent studies have suggested generation multi-innervated spines (MIS), form several excitatory presynaptic inputs onto one spine, hippocampal memory storage. However, little is known about molecular mechanisms underlying MIS formation their contribution to LTP. Using 3D...
Increasing evidence supports a role for deficient Wnt signaling in Alzheimer's disease (AD). Studies reveal that the secreted antagonist Dickkopf-3 (DKK3) colocalizes to amyloid plaques AD patients. Here, we investigate contribution of DKK3 synapse integrity healthy and brains. Our findings show expression is upregulated brains subjects protein levels increase at early stages disease. In hAPP-J20 hAPPNL-G-F/NL-G-F mouse models, extracellular are increased accumulates dystrophic neuronal...
Extracellular vesicles (EVs) play a crucial role in intercellular communication, participating the paracrine trophic support or propagation of toxic molecules, including proteins. RTP801 is stress-regulated protein, whose levels are elevated during neurodegeneration and induce neuron death. However, whether toxicity transferred trans-neuronally via EVs remains unknown. Hence, we overexpressed silenced protein cultured cortical neurons, isolated their derived (RTP801-EVs shRTP801-EVs,...
RTP801/REDD1 is a stress-regulated protein whose upregulation necessary and sufficient to trigger neuronal death in vitro vivo models of Parkinson's Huntington's diseases up regulated compromised neurons human postmortem brains both neurodegenerative disorders. Indeed, disease mouse models, RTP801 knockdown alleviates motor-learning deficits.We investigated the physiological role plasticity we found rat, synapses. The absence enhanced excitatory synaptic transmission cultures brain slices...
RTP801/REDD1 is a stress-regulated protein whose levels are increased in several neurodegenerative diseases such as Parkinson's, Alzheimer's, and Huntington's (HD). RTP801 downregulation ameliorates behavioral abnormalities mouse models of these disorders. In HD, mediates mutant huntingtin (mhtt) toxicity vitro its human iPSCs, postmortem putamen samples, striatal synaptosomes from the disease. Here, we investigated role hippocampal pathophysiology HD. We found that hippocampus HD patients...
Increasing evidence supports a role for deficient Wnt signaling in Alzheimer’s disease (AD). Studies reveal that the secreted antagonist Dickkopf-3 (DKK3) colocalizes to amyloid plaques AD patients. Here, we investigate contribution of DKK3 synapse integrity healthy and brains. Our findings show expression is upregulated brains subjects protein levels increase at early stages disease. In hAPP-J20 hAPP NL-G-F/NL-G-F models, extracellular are increased accumulates dystrophic neuronal processes...
ABSTRACT Growing evidence supports a role for deficient Wnt signalling in Alzheimer′s disease (AD). First, the antagonist DKK1 is elevated AD brains and required amyloid-β-induced synapse loss. Second, LRP6 co-receptor integrity three variants of this receptor are linked to late-onset AD. However, expression/role other components remain poorly explored receptors Frizzled1 (Fzd1), Fzd5, Fzd7 Fzd9 interest due their formation/plasticity. Our analyses showed reduced FZD1 FZD7 mRNA levels...
ABSTRACT RTP801/REDD1 is a stress-regulated protein whose upregulation necessary and sufficient to trigger neuronal death in vitro vivo models of Parkinson’s Huntington’s diseases up regulated compromised neurons human postmortem brains both neurodegenerative disorders. Indeed, disease mouse models, RTP801 knockdown alleviates motor-learning deficits. Here, we investigated the physiological role plasticity. found rat, synapses. The absence enhanced excitatory synaptic transmission cultures...
RTP801/REDD1 is a stress-regulated protein whose levels are increased in several neurodegenerative diseases such as Parkinson’s, Alzheimer’s, and Huntington’s (HD). RTP801 downregulation ameliorates behavioral abnormalities mouse models of these disorders. In HD, mediates mutant huntingtin (mhtt) toxicity vitro its human iPSCs, postmortem putamen samples striatal synaptosomes from the disease. Here, we investigated role hippocampal pathophysiology HD. We found...
Abstract Background Extracellular vesicles (EVs) play a crucial role in intercellular communication, participating the paracrine trophic support or propagation of toxic molecules, including proteins. RTP801 is stress-regulated protein, whose levels are elevated during neurodegeneration and induce neuron death. However, whether toxicity transferred trans-neuronally via EVs remains unknown. Methods We overexpressed silenced protein cultured cortical neurons isolated neural-derived (RTP801-EVs,...
Increasing evidence supports a role for deficient Wnt signaling in Alzheimer’s disease (AD). Studies reveal that the secreted antagonist Dickkopf-3 (DKK3) colocalizes to amyloid plaques AD patients. Here, we investigate contribution of DKK3 synapse integrity healthy and brains. Our findings show expression is upregulated brains subjects protein levels increase at early stages disease. In hAPP- J20 hAPP NL-G-F/NL-G-F models, extracellular are increased accumulates dystrophic neuronal...