Gonzalo Arboleda

Gonzalo Arboleda
National University of Colombia | UNAL · Instituto de Genética - IGUN (Bogotá)

MD MSc PhD

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87
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Publications

Publications (87)
Article
Background Large-scale Parkinson's disease (PD) genome-wide association studies (GWAS) have, until recently, only been conducted on subjects with European-ancestry. Consequently, polygenic risk scores (PRS) constructed using PD GWAS data are likely to be less predictive when applied to non-European cohorts. Methods Using GWAS data from the largest...
Article
Full-text available
Gliomas represent 70% of all central system nervous tumors and are classified according to the degree of malignancy as low- or high-grade. The permanent activation of the EGFR/PI3K/AKT pathway by various genetic or post-translational alterations of EGFR, PI3KCA, and PTEN has been associated with increased proliferation and resistance to apoptosis....
Preprint
Full-text available
Background: Large-scale Parkinson's disease (PD) genome-wide association studies (GWAS) and meta-analyses have, until recently, only been conducted on subjects with European-ancestry. Consequently, polygenic risk scores (PRS) constructed using PD GWAS data are likely to be less predictive when applied to non-European cohorts. Methods: Using GWAS da...
Article
Full-text available
In adulthood, the ability to digest lactose, the main sugar present in milk of mammals, is a phenotype (lactase persistence) observed in historically herder populations, mainly Northern Europeans, Eastern Africans, and Middle Eastern nomads. As the –13910 ∗ T allele in the MCM6 gene is the most well-characterized allele responsible for the lactase...
Article
Objective: This work was undertaken in order to identify Parkinson's disease (PD) risk variants in a Latino cohort, to describe the overlap in the genetic architecture of PD in Latinos compared to European-ancestry subjects, and to increase the diversity in PD genome-wide association (GWAS) data. Methods: We genotyped and imputed 1497 PD cases a...
Article
Nuclear receptors are ligand-activated transcription factors that can modulated cellular processes involved in the development, homeostasis, cell proliferation, metabolism, and reproduction through the control of the specific genetic and molecular program. In the central nervous system, they are key regulators of neural stem cell fate decisions and...
Article
Alzheimer’s disease (AD) is the main cause of dementia in the world. Studies of human AD brains show abnormalities in the white matter and reduction of myelin and oligodendrocyte markers. It has been proposed that oligodendrocyte progenitor cells (OPCs) present in the adult brain are a potential source for re-myelination, through proliferation and...
Article
Background: Parkinson's disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinson's disease in non-European populations. In addition, the overall identification of copy number variants at a genome-wide level has been understudied in Parkinson's p...
Preprint
Full-text available
To date, over 90 Parkinson’s disease (PD) risk variants have been reported from genome-wide association studies (GWAS). However, these GWAS efforts have been limited to individuals of European and East Asian ancestry. We performed the first GWAS of Latino PD patients from South America, comparing 807 cases against 690 controls followed by associati...
Article
Recently, mutations in the RNA polymerase III subunit A (POLR3A) have been described as the cause of the neonatal progeria or Wiedemann-Rautenstrauch syndrome (WRS). POLR3A has important roles in transcription regulation of small RNAs, including tRNA, 5S rRNA, and 7SK rRNA. We aim to describe the cellular and molecular features of WRS fibroblasts....
Preprint
Full-text available
Background: Parkinson's disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinson's disease in non-European populations. In addition, the overall identification of copy number variants at a genome-wide level has been understudied in Parkinson's di...
Preprint
Full-text available
Recently, mutations in the RNA polymerase III subunit 3A (POLR3A) have been described as the cause of the neonatal progeria or Wiedemann-Rautenstrauch syndrome (WRS). POLR3A have important roles in the regulation of transcription of small RNAs, including tRNA, 5S rRNA and U6 snRNA. We aim to describe cellular and molecular features of WRS fibroblas...
Article
Full-text available
The Caribbean soft coral Erythropodium caribaeorum is a rich source of erythrolides—chlorinated briarane diterpenoids. These compounds have an ecological role as feeding deterrents, with a wide variation in their composition depending on the location where the sample is collected. In Colombia, this soft coral can be found at different locations in...
Article
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PTEN-induced kinase 1 (PINK1) mutations can cause early-onset Parkinson’s disease and patients are likely to develop cognitive decline, depression, and dementia. Several neurophysiological studies have demonstrated PINK1 deficiency impairs striatal and hippocampal presynaptic plasticity. Dendritic spine postsynaptic abnormalities are common in neur...
Article
Full-text available
Introduction Bexarotene, a retinoid X receptor agonist, improves cognition in murine models of Alzheimer’s disease (AD). This study evaluated the effects of bexarotene on pathological and electrophysiological changes in very old triple transgenic AD mice (3xTg-AD mice). Methods 24-month-old 3xTg-AD mice were treated with bexarotene (100 mg/kg/day...
Article
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X-linked inhibitor of apoptosis protein (XIAP) is an emerging crucial therapeutic target in cancer. We report on the discovery and characterisation of small organic molecules from Piper genus plants exhibiting XIAP antagonism, namely erioquinol, a quinol substituted in the 4-position with an alkenyl group and the alkenylphenols eriopodols A–C. Anot...
Article
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Introducción. Los proyectos del mapa de haplotipos (HapMap) y de los 1.000 genomas han sido fundamentales para la compresión del componente genético de las enfermedades comunes y los fenotipos normales. Sin embargo, la variabilidad genética colombiana incluida en estos proyectos no es representativa del país. Objetivo. Contribuir al conocimiento de...
Article
Background Wiedemann-Rautenstrauch syndrome (WRS) is a form of segmental progeria presenting neonatally, characterised by growth retardation, sparse scalp hair, generalised lipodystrophy with characteristic local fatty tissue accumulations and unusual face. We aimed to understand its molecular cause. Methods We performed exome sequencing in two fa...
Article
Objective: We evaluated the association of several single-nucleotide polymorphisms in the triggering receptor expressed on myeloid cells 2 (TREM2) gene in a Colombian sample of late-onset Alzheimer disease (LOAD). Methods: The p.Q33* (rs104894002), p.R47H (rs75932628), p.R62H (rs143332484), and p.D87N (rs142232675) variants of TREM2 gene were di...
Article
Full-text available
Historically, knowledge of ethnobotany, which has revealed different phytochemical and pharmacological compounds from traditional plants, has formed the basis for new anticancer drug discovery. The use of some Piper species in traditional medicine against cancer, suggests that genus Piper is a promising source of new compounds with anticancer activ...
Article
Full-text available
Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by beta-amyloid (Aβ) accumulation and neurofibrillary tangles formation in the brain which are associated to synaptic deficits and dementia. Liver X receptor (LXR) agonists have been demonstrated to revert of pathologic and cognitive defects in murine models of AD thr...
Article
Full-text available
Introducción. Los gliomas son los tumores primarios más comunes del sistema nervioso central y se clasifican de I a IV según su grado de malignidad. En recientes investigaciones se ha encontrado que su aparición está relacionada con mutaciones en el exón 4 de los genes que codifican las deshidrogenasas de isocitrato 1 y 2 (IDH1: codón 132; IDH2: co...
Chapter
During development and through adulthood, differentiation of diverse cell types is controlled by specific genetic and molecular programs for which transcription factors are master regulators of gene expression. Here, we present an overview of the role of nuclear receptors and their selective pharmacological modulators in oligodendrocytes linage, th...
Article
The vascular hypothesis of Alzheimer's disease postulates that disruption of the brain microvasculature is important for the accumulation of amyloid beta and increased neuroinflammation. Liver X Receptor agonist, GW3965, has been demonstrated to successfully modulate neuroinflammation and lipid metabolism in murine models of AD. This is partially d...
Article
Objective: We evaluated the association of several single-nucleotide polymorphisms in different genes including APOE, TOMM40, CR1, PVRL2, SORL1, PICALM, and GWA_14q32.13 in a Colombian sample of Late-Onset Alzheimer disease (LOAD) patients. Methods: A case-control study was conducted in 362 individuals (181 LOADs and 181 controls) to determine t...
Article
Full-text available
The liver X receptor agonist, GW3965, improves cognition in Alzheimer's disease (AD) mouse models. Here, we determined if short-term GW3965 treatment induces changes in the DNA methylation state of the hippocampus, which are associated with cognitive improvement. Twenty-four-month-old triple-transgenic AD (3xTg-AD) mice were treated with GW3965 (50...
Article
Full-text available
Alzheimer's disease (AD) is the major cause of dementia worldwide. The pharmacological activation of nuclear receptors (Liver X receptors: LXRs or Retinoid X receptors: RXR) has been shown to induce overexpression of the ATP-Binding Cassette A1 (ABCA1) and Apolipoprotein E (ApoE), changes that are associated with improvement in cognition and reduct...
Data
ApoE immunoreactivity increases in GCL but not in the ML of DG in GW3965-treated 3xTg-AD. (Figure A) Representative micrographs of GFAP (Red) and ApoE (Green) immunohistochemistry using confocal microscopy showing DG subregion, (Figure B) RFI of ApoE in the ML of DG of the hippocampus. (Figure C) RFI of ApoE in the GCL of DG of the hippocampus. Dat...
Data
LXR agonist increases ApoE in NeuN positive cell without any increase of the neuronal cells number. (Figure A, Figure B, Figure C and Figure D) Representative micrographs of NeuN (Red), ApoE (Green) immunofluorescence and Hoechst (Blue) using confocal microscopy on x20 of magnification in DG, CA3 and CA1 of the hippocampus. (Figure E) Representativ...
Data
High concentration of neither oAβ42 or oAβ42 plus GW3965 affect single evokedCA1 fEPSPs. fEPSPs slope over time after the following treatments: 1) 200 nM oAβ42 [n = 4—black dots] for 40 min and 2) 0.1 μM GW3965 (1 hour incubation before recording) and 40 min 200 nM oAβ42 [n = 4—red dots]. (PDF)
Data
No detectable reduction in amyloid beta. Amyloid plaque deposition in brains of treated and untreated mice groups were evaluated by Thio-S staining. (Figure A and Figure B) Representative micrographs of brain stained sections. Data were expressed as mean ± S.E.M. Statistical analysis was done by one way ANOVA followed by Tukey's multiple comparison...
Data
GW3965 treatment did not reduce amyloid plaque area in Subiculum, CA1 of the hippocampus and Entorhinal cortex in 3xTg-AD mice. Amyloid plaque deposition in brains of treated and untreated mice groups were evaluated byimmunohistochemistry with antibody anti-Aβ (6E10). (Figure A) Representative pictograms of Aβ immunohistochemistry from regions of i...
Data
Differentially methylated Illumina probes of 3xTg-AD group treated with LXR agonist in comparison with DMSO-treated 3xTg-AD group
Article
Full-text available
Introduction: Mutations in the leucine-rich repeat kinase 2 gene (LRRK2 or Dardarin) are considered to be a common cause of autosomal dominant and sporadic Parkinson´s disease, but the prevalence of these mutations varies among populations. Objective: to analyzed the frequency of the LRRK2 p.G2019S mutation (c.6055 G>A transition) in a sample of...
Conference Paper
Krabbe disease (KD) patients accumulate psychosine (galactosylsphingosine), a cytotoxic metabolite for oligodendrocytes, inducing early demyelination. Apoptosis has been suggested that plays an important role in psychosine-induced oligodendrocytes cell death in culture and in brains of Krabbe patients and an animal model of the disease (twitcher mo...
Article
The etiology of Parkinson's disease remains unknown. Mutations in PINK1 have provided an understanding of the molecular mechanisms of this pathology. PINK1 and Parkin are important in the dismissal of dysfunctional mitochondria. However, the role of PINK1 in the control of neuronal survival pathways is not clear. To determine the role of PINK1 in t...
Article
It is now well established that mitochondria are organelles that, far from being static, are subject to a constant process of change. This process, which has been called mitochondrial dynamics, includes processes of both fusion and fission. Loss of Pink1 (PTEN-induced putative kinase 1) function is associated with early onset recessive Parkinson's...
Article
Full-text available
p>La enfermedad de Parkinson es un desorden neurodegenerativo complejo, caracterizado por la pérdida progresiva de las neuronas dopaminérgicas de la sustancia nigra pars compacta. Factores tanto ambientales como genéticos se ha determinado que contribuyen a su desarrollo. Mutaciones en los genes PINK1 y PARKIN han sido asociadas con la enfermedad d...
Article
Parkinson's disease is a complex neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons of the substance nigra pars compacta. It has been determined that factors both environmental and genetic contribute to its development. Mutations in the genes PINK1 and PARKIN have been associated with the early onset of diseas...
Article
Introducción Los gliomas son los tumores más frecuentes del sistema nervioso central y representan una de las principales causas de mortalidad por cáncer. Diversas alteraciones moleculares han sido descritas en el proceso de gliogénesis, incluyendo alteraciones en la vía de señalización EGFR/PI3K/AKT, ya que promueve la supervivencia e inhibición d...
Article
The etiology of Parkinson's disease (PD) remains unknown. Mutations in several genes, including PINK1, have provided an understanding of the molecular mechanisms of this pathology. We analyzed the role of PINK1 overexpression (wild-type PINK1 or PINK1 with G309D or L347P mutations) on neurotoxicity associated with C2-ceramide exposure in CAD cells....
Article
The Wiedemann-Rautenstrauch syndrome (WRS) (OMIM 264090) is a rare progeroid entity. WRS patients are characterized by premature aging present at birth including pseudohydrocephalus, cranio-facial disproportion, reduced subcutaneous fat, thin skin, rigid and thick joints, and neonatal teeth in some cases. Here we describe three sibs with WRS from u...
Article
Evidence has implicated apoptosis as a mechanism underlying cell demise in diverse neurodegenerative diseases including Parkinson's disease (PD). Endogenous toxins and other stress signals activate the sphingomyelin pathway increasing the levels of ceramide, an important regulator of cell death. In the present paper we have analysed the contributio...
Article
Full-text available
Keywordshuman genetics-candidate genes-Latin America-Parkinson’s disease-polymorphisms
Article
Krabbe disease is an inherited lysosomal disorder in which galactosylsphingosine (psychosine) accumulates mainly in the central nervous system. To gain insight into the possible mechanism(s) that may be participating in the inhibition of the postnatal somatic growth described in the animal model of this disease (twitcher mouse, twi), we studied the...
Article
The Wiedemann-Rautenstrauch syndrome (WRS, OMIM: 264090) characterizes a premature aging syndrome in which several features of aging are apparent at birth. We did not find mutations in Lamin A/C (LMNA) gene in four WRS patients, and in particular, we did not find the G608G mutation (GGC > GGT transition) which is associated with most cases with Hut...
Article
Full-text available
Attention-deficit hyperactivity disorder (ADHD) is an important psychiatric condition in terms of its prevalence and impact on quality of life. It has one of the highest heritabilities found in psychiatric disorders. A number of association studies exploring several candidate genes in different populations around the world have been carried out. Th...
Article
Full-text available
Recientemente se ha definido el papel decisivo que tienen las mitocondrias en los mecanismos de muerte celular, los cuales se han explicado en diversos modelos, donde la permeabilización de la membrana externa mitocondrial y la liberación de proteínas importantes del espacio intermembranal de la mitocondria son características importantes que defin...
Article
Full-text available
The present review explores the role of ceramides in neuronal apoptosis, as well as the recent discovery of the signaling pathways involved in this process placing particular emphasis on the correlation between cellular metabolism and neuronal death. Endogenous levels of ceramides are increased following various pro-apoptotic stimuli which have bee...
Article
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El presente artículo explora el papel que desempeña el folato como conocido metabolito del ciclo de un carbono (OCM, del inglés onecarbon metabolism) en la alteración de la integridad de las células nerviosas. Aquí se discute evidencia reciente de la literatura que muestra la reparación del ADN como un proceso relacionado con la apoptosis neuronal...
Article
Full-text available
RESUMEN El presente artículo explora el papel que desempeña el folato como conocido metabo-lito del ciclo de un carbono (OCM, del inglés one-carbon metabolism) en la altera-ción de la integridad de las células nerviosas. Aquí se discute evidencia reciente de la literatura que muestra la reparación del ADN como un proceso relacionado con la apoptosi...
Article
The Wiedemann-Rautenstrauch syndrome (WRS) characterises a premature aging syndrome in which several features of human aging are apparent at birth therefore allowing their grouping as a neonatal progeroid condition. This differentiates WRS from other progeroid entities such as Hutchinson-Gilford progeria syndrome (HGPS) in which characteristics of...
Article
Full-text available
Introducción. La trisomía 21 libre es responsable del 95% de los casos de síndrome de Down. La edad materna y la recombinación son los principales factores de riesgo asociados con la concepción de estos individuos. El origen materno de la trisomía ocurre en el 90% de los casos, mientras que los casos de origen paterno y mitótico comparten un 10%. P...
Article
Evidence has implicated apoptosis as a mechanism underlying cell death in diverse neurodegenerative diseases including Parkinson's disease (PD). Endogenous agents such as TNF-alpha, INF-gamma, IL-1beta and others stress signals activate the sphingomyelin pathway increasing ceramide levels. Ceramide triggers apoptotic pathways while inhibiting survi...
Article
Ceramide is a lipid second-messenger generated in response to stimuli associated with neurodegeneration that induces apoptosis, a mechanism underlying neuronal death in Parkinson's disease. We tested the hypothesis that insulin-like growth factor-1 (IGF-1) could mediate a metabolic response in CAD cells, a dopaminergic cell line of mesencephalic or...
Article
Full-text available
Free trisomy 21 is responsible for 95% of Down syndrome cases. Advanced maternal age and susceptible recombination patterns are recognized risk factors associated to Down syndrome. Maternal origin of trisomy occurs in approximately 90% of cases; paternal and mitotic origin share the remaining 10%. However, the recombination events that serve as a r...
Article
Genetic analysis of human longevity may be useful for the understanding of molecular mechanisms implicated in age-related diseases. The molecular genetics of human longevity is largely unexplored in Latin American populations and other developing countries. To explore the possibility of an association of common polymorphisms in two candidate genes...
Article
Full-text available
Analysis of genetic susceptibility factors for Alzheimer's disease (AD) in populations with different genetic and environmental background may be useful to understand AD etiology. There are few genetic association studies of AD in Latin America. In the present work, we analyzed polymorphisms in 3 candidate genes; the LDL receptor related protein-1,...
Article
In recent years, it has been proposed that synaptic dysfunction may be an important etiological factor for Alzheimer's disease (AD). This hypothesis has important implications for the analysis of AD genetic risk in case-control studies. In the present work, we analyzed common functional polymorphisms in three synaptic plasticity-related genes (brai...
Article
Cellular apoptosis has been considered as themain physiological mechanism underlyingneuronal demise associated to neurodegenerativediseases. Apoptosis has also been described inparenquimal and microvascular endotheliumin the acute phase of sepsis during multi-organicdysfunction. Therefore, strategies aimed toMuerte celular: blanco terapéutico enneu...
Article
Wiedemann-Rautenstrauch syndrome (WRS) characterizes a neonatal progeroid entity. In the last 30 years, 28 cases have been reported. In most cases of WRS, survival is short and long-term studies are impossible. In the present report, we describe a patient with WRS followed for 17 years at the Instituto de Genética, Universidad Nacional de Colombia;...
Article
La cemida es un producto del metabolismo de los esfingolípidos, que induce diversas respuestas celulares incluyendo la apoptosis. Debido a que diversas señales de estrés celular consideradas mediadores de la muerte neuronal dopaminérgica (citoquinas, citotóxicos y estrés ambiental), incrementan el nivel de ceramidas.
Article
La Enfermedad de Parkinson (EP) es una de las principales enfermedades neurodegenerativas en el mundo, con un gran impacto sobre los pacientes y sus familias. Aunque sus aspectos genéticos han sido analizados ampliamente en otros países y se han encontrado como cruciales en la patogénesis, no hay estudiso al respecto reportados en Latinoamérica.