A5081313788- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Cholinesterase and Neurodegenerative Diseases
- Endoplasmic Reticulum Stress and Disease
- ATP Synthase and ATPases Research
- Neurological disorders and treatments
- Nuclear Receptors and Signaling
- Lysosomal Storage Disorders Research
- Lipid Membrane Structure and Behavior
- Prion Diseases and Protein Misfolding
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Cellular transport and secretion
- Adipose Tissue and Metabolism
- Cholesterol and Lipid Metabolism
- Protein Tyrosine Phosphatases
- Ubiquitin and proteasome pathways
- Enzyme Catalysis and Immobilization
- Intracerebral and Subarachnoid Hemorrhage Research
- Wnt/β-catenin signaling in development and cancer
- Genetics and Neurodevelopmental Disorders
- Botulinum Toxin and Related Neurological Disorders
- Drug Transport and Resistance Mechanisms
- Neurological diseases and metabolism
Columbia University Irving Medical Center
2012-2025
Columbia University
2012-2024
Gènes, synapses et cognition
2019
Neurology, Inc
2019
Hospital de Sant Pau
2008-2014
Hospital Universitario Ramón y Cajal
2014
Hospital Universitari Germans Trias i Pujol
2014
Hospital Universitari Arnau de Vilanova
2014
Complejo Hospitalario Universitario de Santiago
2014
Biogipuzkoa Health Research Institute
2014
Neural cells derived from induced pluripotent stem patients with genetic forms of Parkinson’s disease provide insights into pathogenesis.
Familial Parkinson disease is associated with mutations in α-synuclein (α-syn), a presynaptic protein that has been localized not only to the cytosol, but also mitochondria. We report here wild-type α-syn from cell lines, and brain tissue humans mice, present mitochondria rather mitochondria-associated endoplasmic reticulum (ER) membranes (MAM), structurally functionally distinct subdomain of ER. Remarkably, we found pathogenic point human result its reduced association MAM, coincident lower...
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 ,...
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 protein alpha-synuclein (αSyn) plays a pivotal role in the pathogenesis of synucleinopathies, including Parkinson's disease and multiple system atrophy, with growing evidence indicating that lipid dyshomeostasis is key phenotype these neurodegenerative disorders. Previously, we identified αSyn localizes, at least part, to mitochondria-associated endoplasmic reticulum membranes (MAMs), which are transient functional domains containing proteins regulate metabolism, de novo synthesis...
Activity-dependent gene expression mediating changes of synaptic efficacy is important for memory storage, but the mechanisms underlying transcriptional in age-related disorders are poorly understood. In this study, we report that transcription mediated by cAMP-response element binding protein (CREB)-regulated coactivator CRTC1 impaired neurons and brain from an Alzheimer9s disease (AD) transgenic mouse expressing human β-amyloid precursor (APP<sub>Sw,Ind</sub>). Suppression CRTC1-dependent...
Maintaining a pool of functional mitochondria requires degradation damaged ones within the cell. PINK1 is critical in this quality-control process: loss mitochondrial membrane potential causes to accumulate on surface, triggering mitophagy. However, little known about how regulated. Recently, we showed that content kept low healthy by continuous ubiquitination and proteasomal its mature form via mechanism inconsistent with proposed N-end rule process. Using both human female monkey cell...
Abstract Inherited familial Alzheimer's disease (AD) is characterized by small increases in the ratio of Aβ42 versus Aβ40 peptide which thought to drive amyloid plaque formation brain these patients. Little known however whether ageing, major risk factor for sporadic AD, affects beta‐peptide (Aβ) generation as well. Here we demonstrate that secretion Aβ enhanced an vitro model neuronal correlating with increase γ‐secretase complex formation. Moreover found peroxynitrite (ONOO − ), produced...
Along with Parkin, PINK1 plays a critical role in maintaining mitochondrial quality control. Although is expressed constitutively, its level kept low healthy mitochondria by polyubiquitination and ensuing proteasomal degradation of mature, 52 kDa, form. We show here that the target mature form mediated ubiquitination conserved lysine at position 137. Notably, full-length protein also contains Lys-137 but not ubiquitinated. On basis our data, we propose cleavage Phe-104 disrupts major...
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...
Background: The role of the lipidome as a biomarker for Parkinson’s disease (PD) is relatively new field that currently only focuses on PD diagnosis. Objective: To identify relevant signature severity markers. Methods: Disease 149 patients was assessed by Unified Rating Scale (UPDRS) and Montreal Cognitive Assessment (MoCA). lipid composition whole blood samples analyzed, consisting 517 species from 37 classes; these included all major classes glycerophospholipids, sphingolipids,...
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...
We describe a Spanish family in which 3 of 4 siblings had dementia with Lewy bodies, 2 them starting at age 26 years and the other 29 years. The father has recently been diagnosed body disease, onset 77 Neuropathological examination brain index patient disclosed unusual features characterized by diffuse disease generalized neurofibrillary tangle pathology but no amyloid deposits any region. Moreover, colocalized tangles most affected neurons. Mutation screening that included all coding exons...