Enrique SantamaríaNavarrabiomed
Enrique Santamaría
PhD
About
257
Publications
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Introduction
Additional affiliations
June 2011 - June 2013
January 2011 - May 2016
Publications
Publications (257)
Deep brain stimulation (DBS) is a neurosurgical procedure that provides therapeutic benefits for movement and affective disorders. The nucleus basalis of Meynert (NBM) and substantia nigra (SN) are considered target areas to apply DBS. Even though the degeneration of NBM and SN underlies the cognitive decline observed in neurological diseases, the...
Astrocytes are considered an essential source of blood-borne glucose or its metabolites to neurons. Nonetheless, the necessity of the main astrocyte glucose transporter, i.e., GLUT1, for brain glucose metabolism has not been defined. Unexpectedly, we found that brain glucose metabolism was paradoxically augmented in mice with astrocytic GLUT1 reduc...
Postoperative delirium (POD) is a common and serious neuropsychiatric syndrome that leads to higher morbidity and mortality. We investigated the association between serum C-reactive protein (CRP) and the occurrence of POD in older hip fracture patients, and whether CRP predicted POD better than a clinical model.
Patients aged ≥ 75 years admitted fo...
Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease with a mean survival time of three years. The 97% of the cases have TDP-43 nuclear depletion and cytoplasmic aggregation in motor neurons. TDP-43 prevents non-conserved cryptic exon splicing in certain genes, maintaining transcript stability, including ATG4B, which is crucia...
RTP801/REDD1 is a stress-responsive protein overexpressed in neurodegenerative diseases such as Alzheimer’s disease (AD) that contributes to cognitive deficits and neuroinflammation. Here, we found that RTP801 interacts with HSPC117, DDX1 and CGI-99, three members of the tRNA ligase complex (tRNA-LC), which ligates the excised exons of intron-conta...
Many cancer patients do not benefit from PD-L1/PD-1 blockade immunotherapies. PD-1 and LAG-3 co-upregulation in T-cells is one of the major mechanisms of resistance by establishing a highly dysfunctional state in T-cells. To identify shared features associated to PD-1/LAG-3 dysfunctionality in human cancers and T-cells, multiomic expression profile...
Background
Sarcopenia, the gradual and generalized loss of muscle mass and function with ageing, is one of the major health problems in older adults, given its high prevalence and substantial socioeconomic implications. Despite the extensive efforts to reach consensus on definition and diagnostic tests and cut‐offs for sarcopenia, there is an urgen...
Huntington’s disease (HD) is a neurological disorder caused by a CAG expansion in the Huntingtin gene ( HTT ). HD pathology mostly affects striatal medium-sized spiny neurons and results in an altered cortico-striatal function. Recent studies report that motor skill learning, and cortico-striatal stimulation attenuate the neuropathology in HD, resu...
The standard of care for glioblastoma (GBM) involves surgery followed by adjuvant radio-and chemotherapy, but often within months, patients relapse, and this has been linked to glioma stem cells (GSCs), self-renewing cells with increased therapy resistance. The identification of the epidermal growth factor receptor (EGFR) and platelet-derived growt...
Leucine-rich repeat kinase 2 (LRRK2) inhibition is a promising disease-modifying therapy for LRRK2-associated Parkinson disease (L2PD) and idiopathic PD (iPD). Yet, pharmaco-dynamic readouts and progression biomarkers for disease modification clinical trials are insufficient. Employing phospho-/proteomic analyses we assessed the impact that LRRK2 a...
Alzheimer's disease (AD) is a neurodegenerative olfactory disorder affecting millions of people worldwide. Alterations in the hexosamine-or glucose-related pathways have been described through AD progression. Specifically, an alteration in glucosamine 6 phosphate isomerase 2 (GNPDA2) protein levels has been observed in olfactory areas of AD subject...
Alzheimer's disease (AD) is the most common form of dementia, characterized by an early olfactory dysfunction, progressive memory loss, and behavioral deterioration. Albeit substantial progress has been made in characterizing AD‐associated molecular and cellular events, there is an unmet clinical need for new therapies. In this study, olfactory tra...
Huntington’s disease (HD) is a neurological disorder caused by a CAG expansion in the Huntingtin gene ( HTT ). HD pathology mostly affects striatal medium-sized spiny neurons and results in an altered cortico-striatal function. Recent studies report that motor skill learning, and cortico-striatal stimulation attenuate the neuropathology in HD, resu...
Alzheimer's disease (AD) is a neurodegenerative olfactory disorder affecting millions of people worldwide. Alterations in the hexosamine or glucose-related pathways have been described through AD progression. Specifically, an alteration in glucosamine 6 phosphate isomerase 2 (GNPDA2) protein levels has been observed in olfactory areas from AD subje...
Introduction: Due to the segmented functions and complexity of the human brain, the characterization of molecular profiles within specific areas such as brain structures and biofluids is essential to unveil the molecular basis for structure specialization as well as the molecular imbalance associated with neurodegenerative and psychiatric diseases....
Many angles of personalized medicine, such as diagnostic improvements, systems biology [...]
Postoperative delirium (POD) is a common neuropsychiatric complication in geriatric inpa- tients after hip fracture surgery and its occurrence is associated with poor outcomes. The purpose of this study was to investigate the relationship between pre- operative biomarkers in serum and cerebrospinal fluid (CSF) and the development of POD in older hi...
Postoperative delirium (POD) is a common neuropsychiatric complication in geriatric inpatients after hip fracture surgery and its occurrence is associated with poor outcomes. The purpose of this study was to investigate the relationship between preoperative biomarkers in serum and cerebrospinal fluid (CSF) and the development of POD in older hip fr...
Extracellular vesicles (EVs) play a crucial role in intercellular communication, participating in the paracrine trophic support or in the propagation of toxic molecules, including proteins. RTP801 is a stress‐regulated protein, whose levels are elevated during neurodegeneration and induce neuron death. However, whether RTP801 toxicity is transferre...
Background
Aortic stenosis (AS) is characterized by inflammation, fibrosis, osteogenesis and angiogenesis. Men and women develop these mechanisms differently. Galectin-3 (Gal-3) is a pro-inflammatory and pro-osteogenic lectin in AS. In this work, we aim to analyse a potential sex-differential role of Gal-3 in AS.
Methods
226 patients (61.50% men)...
Osteoporosis is a skeletal disease that can increase the risk of fractures, leading to adverse health and socioeconomic consequences. However, current clinical methods have limitations in accurately estimating fracture risk, particularly in older adults. Thus, new technologies are necessary to improve the accuracy of fracture risk estimation. In th...
Drug combinations are key to circumvent resistance mechanisms compromising response to single anti-cancer targeted therapies. The implementation of combinatorial approaches involving MEK1/2 or KRASG12C inhibitors in the context of KRAS-mutated lung cancers focuses fundamentally on targeting KRAS proximal activators or effectors. However, the antitu...
Alzheimer’s disease (AD) is the most common form of dementia, characterized by an early olfactory dysfunction, progressive memory loss and behavioral deterioration. Albeit substantial progress has been made in characterizing AD-associated molecular and cellular events, there is an unmet clinical need for new therapies. In this work, olfactory tract...
Alzheimer’s disease (AD) is the most common form of dementia, characterized by an early olfactory dysfunction, progressive memory loss and behavioral deterioration. Albeit substantial progress has been made in characterizing AD-associated molecular and cellular events, there is an unmet clinical need for new therapies. In this work, olfactory tract...
Progressive Supranuclear palsy (PSP) is a 4-repeat (4-R) tauopathy. We hypothesized that the molecular diversity of tau could explain the heterogeneity seen in PSP disease progression. To test this hypothesis, we performed an extensive biochemical characterisation of the high molecular weight tau species (HMW-Tau) in 20 different brain regions of 2...
Extracellular vesicles (EVs) are key mediators of cell-to-cell communication. Their content reflects the state of diseased cells representing a window into disease progression. Collagen-VI Related Muscular Dystrophy (COL6-RD) is a multi-systemic disease involving different cell types. The role of EVs in this disease has not been explored. We compar...
Purpose:
Hip fracture is a public health problem worldwide. Traditional prognostic models do not include blood biomarkers, such as those obtained by proteomics. This study aimed to investigate the relationships between serum inflammatory biomarkers and frailty in older adults with hip fracture as well as adverse outcomes at one and three months af...
Resistance of melanoma to targeted therapy and immunotherapy is linked to metabolic rewiring. Here, we show that increased fatty acid oxidation (FAO) during prolonged BRAF inhibitor (BRAFi) treatment contributes to acquired therapy resistance in mice. Targeting FAO using the US Food and Drug Administration-approved and European Medicines Agency-app...
Insulin-like growth factor-I (IGF-I) exerts multiple actions, yet the role of IGF-I from different sources is poorly understood. Here, we explored the functional and behavioral consequences of the conditional deletion of Igf-I in the nervous system (Igf-I Δ/Δ), and demonstrated that long-term potentiation was impaired in hippocampal slices. Moreove...
Background
Postoperative delirium (POD) after hip fracture surgery is a common and serious neuropsychiatric syndrome that leads to higher morbidity and mortality. Current predictive models of delirium are based on clinical factors that can be subjective and imprecise. In this study we investigated the association between serum C-reactive protein (C...
Learning and memory mainly rely on correct synaptic function in the hippocampus and other brain regions. In Parkinson’s disease, subtle cognitive deficits may even precede motor signs early in the disease. Hence, we set out to unravel the earliest hippocampal synaptic alterations associated with human α-synuclein overexpression prior to and soon af...
Resistance mechanisms compromise response to single targeted therapies, favoring the idea that combinatorial strategies are key to circumvent this clinical problem. Combinatorial strategies for cancers driven by oncogenic KRAS based on MEK1/2 or KRASG12C inhibitors have so far incorporated abrogation of KRAS proximal effectors involved in oncogenes...
Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III (ISCIII): Fondo de Investigación Sanitaria y Fondo Europeo de Desarrollo Regional and Proteored Regional Government of Navarra.
Introduction
Atrial fibrillation (AF) is the most common sustained cardiac ar...
Delirium is a neuropsychiatric syndrome associated with increased morbidity and
mortality in older patients. The aim of this study was to review predictive biomarkers
of delirium in older patients to gain insights into the pathophysiology of this
syndrome and provide guidance for future studies. Two authors independently
and systematically searched...
Aims:
(Phospho)proteomics of old-aged subjects without cognitive or behavioral symptoms, and without AD-neuropathological changes and lacking any other neurodegenerative alteration will increase understanding about the physiological state of human brain aging without associate neurological deficits and neuropathological lesions.
Methods:
(Phosph...
Objective: The clinical screening of hip fracture risk is complicated due to the limitations of the reference tools (i.e., bone turnover markers, BMD, FRAX) but with new biomarkers could provide better information for this risk. The present study described emerging biomarkers of the risk of hip fractures with different biomarkers in serum and compa...
Synucleinopathies are a group of neurodegenerative diseases without effective treatment characterized by the abnormal aggregation of alpha-synuclein (aSyn) protein. Changes in levels or in the amino acid sequence of aSyn (by duplication/triplication of the aSyn gene or point mutations in the encoding region) cause familial cases of synucleinopathie...
A complex network of interactions exists between the olfactory, immune and central nervous systems. In this work we intend to investigate this connection through the use of an immunostimulatory odorant like menthol, analyzing its impact on the immune system and the cognitive capacity in healthy and Alzheimer’s Disease Mouse Models. We first found t...
Transcriptomics and phosphoproteomics were carried out in the cerebral cortex of B6.Cg-Mapttm1(EGFP)Klt (tau knockout: tau-KO) and wild-type (WT) 12 month-old mice to learn about the effects of tau ablation. Compared with WT mice, tau-KO mice displayed reduced anxiety-like behavior and lower fear expression induced by aversive conditioning, whereas...
Next-generation proteomics has allowed the implementation of biomedical proteome research to uncover disease-affected protein expression profiles. It has also enabled the determination of protein localization, protein interactomes, posttranslational modifications and protein dysfunction in human diseases. Many pillars in personalized medicine, such...
Background Extracellular vesicles (EVs) play a crucial role in intercellular communication, participating in the paracrine trophic support or in the propagation of toxic molecules, including proteins. RTP801 is a stress-regulated protein, whose levels are elevated during neurodegeneration and induce neuron death. However, whether RTP801 toxicity is...
A significant number of cancer patients do not benefit from PD-L1/PD-1 blockade immunotherapies. PD-1 and LAG-3 co-upregulation in T-cells is one of the major mechanisms of resistance by establishing a highly dysfunctional state in T-cells. To identify shared features associated to PD-1/LAG-3 dysfunctionality in human cancers and T-cells, multiomic...
Background
Smell impairment is one of the earliest features in Alzheimer’s (AD) and Parkinson’s diseases (PD). Due to sex differences exist in terms of smell and olfactory structures as well as in the prevalence and manifestation of both neurological syndromes, we have applied olfactory proteomics to favor the discovery of novel sex-biased physio-p...
Gastric cancer (GC) is a major public health problem worldwide, with high mortality rates due to late diagnosis and limited treatment options. Biomarker research is essential to improve the early detection of GC. Technological advances and research methodologies have improved diagnostic tools, identifying several potential biomarkers for GC, includ...
Docosahexaenoic acid (DHA), the most abundant polyunsaturated fatty acid in the brain, is essential for successful aging. In fact, epidemiological studies have demonstrated that increased intake of DHA might lower the risk for developing Alzheimer’s disease (AD). These observations are supported by studies in animal models showing that DHA reduces...
Background: Smell impairment is one of the earliest features in Alzheimer’s (AD) and Parkinson’s diseases (PD). Due to sex differences exist in terms of smell and olfactory structures as well as in the prevalence and manifestation of both neurological syndromes, we have applied olfactory proteomics to favor the discovery of novel sex-biased physio-...
Delirium is an important cause of morbidity and mortality in older adults admitted to hospital. Multicomponent interventions targeting delirium risk factors, including physical exercise and mobilization, have been shown to reduce delirium incidence by 30–40% in acute care settings. However, little is known about its role in the evolution of deliriu...
Introduction: The amygdala is involved in expression of emotions, memory processing and managing stimulatory input. Amygdala atrophy is evidenced in early stages of Alzheimer’s Disease (AD). Late AD is associated with large amount of A-beta and neurofibrillary tangles composed by hyperphosphorylated Tau aggregates (NFTs) in this area. However, the...
Introduction: One of the most common symptoms in COVID-19 is a sudden loss of smell. SARS-CoV-2 has been detected in the olfactory bulb (OB) from animal models and sporadically in COVID-19 patients. However, the specific role over the SARS-CoV-2 proteome at olfactory level is not known.
Methods: We characterized the in-depth molecular imbalance ind...
Introduction: Smell impairment is one of the earliest features in Alzheimer’s (AD) and Parkinson’s diseases (PD). However, the underlying molecular mechanisms associated to the olfactory dysfunction are poorly understood. To further characterize commonalities and differences during the olfactory neurodegeneration in both neurological syndromes, sex...
Introduction: Glucosamine-6-phosphate isomerase 2 (GNPDA2) participates in the glucose metabolism, converting D-glucosamine-6-phosphate into D-fructose-6-phosphate and ammonium. Traditionally linked to obesity, our group revealed a significant increment in olfactory GNPDA2 protein levels in Alzheimer´s and Parkinson´s diseases. However, the role of...
The relationship between Parkinson’s disease (PD), the second-most common neurodegenerative disease after Alzheimer’s disease, and palmitoylation, a post-translational lipid modification, is not well understood. In this study, to better understand the role of protein palmitoylation in PD and the pathways altered in this disease, we analyzed the dif...
Background: Postoperative delirium (POD) is a common complication in geriatric patients after surgery and its occurrence is associated with poor outcomes. The aim of this study was to evaluate and compare the quality of life (QOL) and the functional and cognitive status of patients with and without POD after hip fracture surgery in a study with 1-a...
Background: Delirium is a common and severe neuropsychiatric syndrome associated with increased morbidity and mortality in older patients. The aim of this study was to identify predictive biomarkers of delirium in older patients through a systematic review and metaanalysis.
Materials and Methods: A systematic review of literature published up to Au...
Post-translational modifications (PTMs) are one of the compulsive and predominant biological processes that regulate the diverse molecular mechanism, modulate the onset of disease, and are the reason behind the functional diversity of proteins. Despite the widespread research findings in neuroproteomics, one of the key drawbacks has been the lack o...
NADPH oxidases (NOX) constitute the main reactive oxygen species (ROS) source in blood vessels. An oxidative stress situation due to ROS overproduction can lead into endothelial dysfunction, a molecular mechanism that precedes cardiovascular diseases (CVDs) such as athero-sclerosis, myocardial infarction, and stroke. NOX5 is the last discovered mem...
The co-administration of glial cell line-derived neurotrophic factor (GDNF) and mesenchymal stem cells (MSCs) in hydrogels (HGs) has emerged as a powerful strategy to enhance the efficient integration of transplanted cells in Parkinson's disease (PD). This strategy could be improved by controlling the cellular microenvironment and biomolecule relea...
The relationship between Parkinson's disease (PD), the second most common neurodegen-erative disease after Alzheimer's disease, and palmitoylation, a post-translational lipid modification, is not well understood. In this study, we have analyzed the differential palmitome present in the cerebral cortex of PD patients compared to controls (n=4 per gr...
Astrocytes are considered an essential source of blood-borne glucose or its metabolites to neurons. Nonetheless, the necessity of the main astrocyte glucose transporter, i.e. GLUT1, for brain glucose metabolism has not been defined. Unexpectedly, we found that brain glucose metabolism was paradoxically augmented in mice with astrocytic GLUT1 ablati...
Post-translational redox modifications provide an important mechanism for the control of major cellular processes. Thioredoxins (Trxs), which are key actors in this regulatory mechanism, are ubiquitous proteins that catalyse thiol-disulfide exchange reactions. In chloroplasts, Trx f, Trx m and NADPH-dependent Trx reductase C (NTRC) have been identi...
One of the most common symptoms in COVID-19 is a sudden loss of smell. SARS-CoV-2 has been detected in the olfactory bulb (OB) from animal models and sporadically in COVID-19 patients. To decipher the specific role over the SARS-CoV-2 proteome at olfactory level, we characterized the in-depth molecular imbalance induced by the expression of GFP-tag...
Circulating tumor cells (CTCs) are the key link between a primary tumor and distant metastases, but once in the bloodstream loss of adhesion induces cell death. To identify mechanisms relevant for melanoma CTC survival we performed RNAseq and discovered that detached melanoma cells and isolated melanoma CTCs rewire lipid metabolism by up-regulating...