A5010705025- Alzheimer's disease research and treatments
- Mitochondrial Function and Pathology
- Cholinesterase and Neurodegenerative Diseases
- Endoplasmic Reticulum Stress and Disease
- Prion Diseases and Protein Misfolding
- Nail Diseases and Treatments
- Cutaneous lymphoproliferative disorders research
- Advancements in Transdermal Drug Delivery
- Neurogenetic and Muscular Disorders Research
- Dermatology and Skin Diseases
- Amyotrophic Lateral Sclerosis Research
- Parkinson's Disease Mechanisms and Treatments
- ATP Synthase and ATPases Research
- Neuroscience and Neuropharmacology Research
- Neonatal skin health care
- Skin Protection and Aging
- Cholesterol and Lipid Metabolism
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Lipid Membrane Structure and Behavior
- Nicotinic Acetylcholine Receptors Study
- Contact Dermatitis and Allergies
- Surfactants and Colloidal Systems
- Plant and Fungal Interactions Research
- Nuclear Receptors and Signaling
- Genetic and rare skin diseases.
Columbia University Irving Medical Center
2015-2025
Universitat Internacional de Catalunya
2020
Columbia University
2018-2020
Hospital de Sant Pau
2009-2013
Universitat Autònoma de Barcelona
2006-2013
Biomedical Research Networking Center on Neurodegenerative Diseases
2011-2013
Consejo Superior de Investigaciones Científicas
1999-2002
Instituto de Investigaciones Químicas y Ambientales de Barcelona
2000
Abstract In the amyloidogenic pathway associated with Alzheimer disease ( AD ), amyloid precursor protein APP ) is cleaved by β‐secretase to generate a 99‐aa C‐terminal fragment (C99) that then γ‐secretase β‐amyloid (Aβ) found in senile plaques. previous reports, we and others have shown activity enriched mitochondria‐associated endoplasmic reticulum ER membranes MAM –mitochondrial connectivity function are upregulated . We now show C99, addition its localization endosomes, can also be ,...
Mitochondrial function is modulated by its interaction with the endoplasmic reticulum (ER). Recent research indicates that these contacts are disrupted in familial models of amyotrophic lateral sclerosis (ALS). We report here this impairment crosstalk between mitochondria and ER impedes use glucose-derived pyruvate as mitochondrial fuel, causing a shift to fatty acids sustain energy production. Over time, deficiency alters electron flow active/dormant status complex I spinal cord tissues,...
Scientific Report12 November 2015Open Access ApoE4 upregulates the activity of mitochondria-associated ER membranes Marc D Tambini Integrated Program in Cellular, Molecular and Biomedical Studies, Columbia University Medical Center, New York, NY, USA Search for more papers by this author Marta Pera Department Neurology, Ellen Kanter Hua Yang Cristina Guardia-Laguarta Pathology Cell Biology, David Holtzman Hope Center Neurological Disorders, Knight Alzheimer's Disease Research Washington...
Background The simultaneous accumulation of different misfolded proteins in the central nervous system is a common feature many neurodegenerative diseases. In most cases, co-occurrence abnormal deposited observed brain regions and cell populations, but, some instances, can be found same cellular aggregates. Co-occurrence tau α-synuclein (α-syn) aggregates has been described disorders with primary deposition α-syn, such as Parkinson's disease dementia Lewy bodies. Although it known that α-syn...
Autosomal-dominant Alzheimer disease (ADAD) is a genetic disorder caused by mutations in Amyloid Precursor Protein (APP) or Presenilin (PSEN) genes. Studies from families with ADAD have been critical to support the amyloid cascade hypothesis of (AD), basis for current development amyloid-based disease-modifying therapies sporadic AD (SAD). However, whether pathological changes APP processing CNS are similar those observed SAD remains unclear. In this study, we measured β-site APP-cleaving...
Article31 August 2020Open Access Source DataTransparent process The Alzheimer's disease-associated C99 fragment of APP regulates cellular cholesterol trafficking Jorge Montesinos Department Neurology, Columbia University Irving Medical Center, New York, NY, USA Search for more papers by this author Marta Pera Delfina Larrea Cristina Guardia-Laguarta Rishi R Agrawal orcid.org/0000-0002-5851-9978 Institute Human Nutrition, Kevin Velasco Taekyung D Yun Irina G Stavrovskaya Yimeng Xu Biomarkers...
Charcot–Marie–Tooth disease (CMT) type 2A is a form of peripheral neuropathy, due almost exclusively to dominant mutations in the nuclear gene encoding mitochondrial protein mitofusin-2 (MFN2). However, there no understanding relationship clinical phenotype genotype. MFN2 has two functions: it promotes inter-mitochondrial fusion and mediates endoplasmic reticulum (ER)–mitochondrial tethering at mitochondria-associated ER membranes (MAM). MAM regulates number key cellular functions, including...
The ε4 allele of apolipoprotein E (APOE) is the dominant genetic risk factor for late-onset Alzheimer's disease (AD). However, reason association between APOE4 and AD remains unclear. While much research has focused on ability apoE4 protein to increase aggregation decrease clearance Aβ, there also an abundance data showing that negatively impacts many additional processes in brain, including bioenergetics. In order gain a more comprehensive understanding APOE4's role pathogenesis, we...
It has been suggested that cellular cholesterol levels can modulate the metabolism of amyloid precursor protein (APP) but underlying mechanism remains controversial. In current study, we investigate in detail relationship between reduction, APP processing and gamma-secretase function cell culture studies. We found mild membrane reduction led to a decrease Abeta(40) Abeta(42) different types. did not detect changes intracellular domain or Notch generation. Western blot analyses showed...
We report the clinical, pathologic, and biochemical characteristics of recently described amyloid precursor protein (APP) I716F mutation. present clinical findings individuals carrying APP mutation neuropathologic examination proband. The was found in a patient with Alzheimer disease onset at age 31 years death 36 who had positive family history early-onset disease. Neuropathologic showed abundant diffuse plaques mainly composed amyloid-beta42 widespread neurofibrillary pathology. Lewy...
Autosomal-dominant Alzheimer's disease (ADAD) is a genetic disorder caused by mutations in Amyloid Precursor Protein (APP) or Presenilin (PSEN) genes. Studying the mechanisms underlying these can provide insight into pathways that lead to AD pathology. The majority of biochemical studies on APP to-date have focused comparing between at different codons. It has been assumed amino acid position major determinant protein dysfunction and clinical phenotype. However, differential effect same...
Recent studies suggest that supplementing intercellular lipids of the stratum corneum in ageing populations or people with dry skin can stimulate functioning skin. This work lends support to reinforcement capacity two different lipid mixtures (synthetic mixtures, SSCL, and internal wool extracts, IWL) formulated as liposomes on healthy differently aged groups individuals. Protection against detergent‐induced dermatitis was evaluated. Transepidermal water loss capacitance were used evaluate...
Calcium signaling in the brain is fundamental to learning and memory process there evidence suggest that its dysfunction involved pathological pathways underlying Alzheimer's disease (AD). Recently, calcium hypothesis of AD has received support with identification non-selective Ca2+-permeable channel CALHM1. A genetic polymorphism (p. P86L) CALHM1 reduces plasma membrane Ca2+ permeability associated an earlier age-at-onset AD. To investigate role variants early-onset (EOAD), we sequenced all...
The present work deals with the ‘in vivo’ stripping technique to evaluate percutaneous absorption of sodium fluorescein (NaFl) vehiculized in two different liposome preparations formed by phosphatidylcholine (PC) and lipids mimicking stratum corneum (SC; ceramides, cholesterol, palmitic acid cholesteryl sulphate), respectively. Furthermore, possible effect these vesicles on SC lipid alkyl chain conformational order were evaluated at depths non-invasive biophysical techniques: Corneometer,...
Oxidative stress is implicated in the pathogenesis of neurodegenerative disorders and hydrogen peroxide (H2O2) plays a central role stress. Huprines, group potent acetylcholinesterase inhibitors (AChEIs), have shown broad cholinergic pharmacological profile. Recently, it has been observed that huprine X (HX) improves cognition non transgenic middle aged mice shows neuroprotective activity (increased synaptophysin expression) 3xTg-AD mice. Consequently, present experiments potential effect...
Intercellular lipids of the stratum corneum (SC) play a crucial role in keeping an optimal skin barrier function and regulating water-holding capacity. Recently, internal have been extracted from wool fibre. This lipid extract has composition similar to that SC lipids. Two parameters were used test effect topically applied (IWL), structured as liposomes, on water functions disturbed intact skin: transepidermal loss capacitance. Liposomes made up simulate also for comparison. The single...
Cellular demands for cholesterol are met by a balance between its biosynthesis in the endoplasmic reticulum (ER) and uptake from lipoproteins. Cholesterol levels intracellular membranes form gradient maintained complex network of mechanisms including control expression, compartmentalization allosteric modulation enzymes that endogenous exogenous sources cholesterol. Low-density lipoproteins (LDLs) internalized delivered to lysosomal compartments release their content, which is then...
<i>Background:</i> Multifactorial diseases such as Alzheimer’s disease (AD) should be more efficiently tackled by drugs which hit multiple biological targets involved in their pathogenesis. We have recently developed a new family of huprine-tacrine heterodimers, rationally designed to upstream and downstream the neurotoxic cascade AD, namely β-amyloid aggregation formation well acetylcholinesterase catalytic activity. <i>Objective:</i> In this study, aim was expand...