A5011440112- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Adipose Tissue and Metabolism
- Neurotransmitter Receptor Influence on Behavior
- Endoplasmic Reticulum Stress and Disease
- Genetics and Neurodevelopmental Disorders
- Glycogen Storage Diseases and Myoclonus
- Autophagy in Disease and Therapy
- Neurological disorders and treatments
- Parkinson's Disease Mechanisms and Treatments
- Autoimmune Neurological Disorders and Treatments
- Ion channel regulation and function
- Peroxisome Proliferator-Activated Receptors
- Bipolar Disorder and Treatment
- Lysosomal Storage Disorders Research
- Treatment of Major Depression
- Biochemical Analysis and Sensing Techniques
- Pancreatic function and diabetes
- Nuclear Receptors and Signaling
- Genetic Neurodegenerative Diseases
- Sirtuins and Resveratrol in Medicine
- Nicotinic Acetylcholine Receptors Study
- Mechanisms of cancer metastasis
- Advanced Glycation End Products research
- Receptor Mechanisms and Signaling
University of Tartu
2009-2024
University College London
2010-2013
National Hospital for Neurology and Neurosurgery
2010
Laboratoire d'Énergétique Moléculaire et Macroscopique, Combustion
2007
Inserm
2007
Institut Galien Paris-Saclay
2007
Recent studies indicate that regulation of cellular oxidative capacity through enhancing mitochondrial biogenesis may be beneficial for neuronal recovery and survival in human neurodegenerative disorders. The peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) has been shown to a master regulator energy metabolism muscle liver. aim our study was establish whether PGC-1alpha PGC-1beta control density also neurons if these coactivators could up-regulated by...
Parkinson disease is characterized by the accumulation of aggregated α-synuclein as major component Lewy bodies. α-Synuclein in turn leads to compensatory effects that may include up-regulation autophagy. Another common feature (PD) mitochondrial dysfunction. Here, we provide evidence overactivation autophagy be a link connects intracellular with We found activation macroautophagy primary cortical neurons overexpress mutant A53T massive destruction and loss, which associated bioenergetic...
Huntington's disease (HD) is a late manifesting neurodegenerative disorder in humans caused by an expansion of CAG trinucleotide repeat more than 39 units gene unknown function. Several mouse models have been reported which show rapid progression phenotype leading to death within 3–5 months (transgenic models) resembling the rare juvenile course HD (Westphal variant) or do not present with any symptoms (knock-in mice). Owing small size brain, mice are suitable for repetitive vivo imaging...
Deficiency of the protein Wolfram syndrome 1 (WFS1) is associated with multiple neurological and psychiatric abnormalities similar to those observed in pathologies showing alterations mitochondrial dynamics. The aim this study was examine hypothesis that WFS1 deficiency affects neuronal function via abnormalities. We show down-regulation neurons leads dramatic changes dynamics (inhibited fusion, altered trafficking, augmented mitophagy), delaying development. induces endoplasmic reticulum...
When ROS production exceeds the cellular antioxidant capacity, cell needs to eliminate defective mitochondria responsible for excessive production. It has been proposed that removal of these involves mitophagy, but mechanism this regulation remains unclear. Here, we demonstrate moderate mitochondrial superoxide and hydrogen peroxide oxidates KEAP1, thus breaking interaction between protein PGAM5, leading inhibition its proteasomal degradation. Accumulated PGAM5 interferes with processing...
Abstract Wolfram syndrome is a rare genetic disease caused by mutations in the WFS1 or CISD2 gene. A primary defect involves poor ER Ca 2+ handling, but how this disturbance leads to not known. The current study, performed neurons, most affected and disease-relevant cells, involving both genes, explains disturbed handling compromises mitochondrial function affects neuronal health. Loss of content impaired ER-mitochondrial contact sites WFS1- CISD2-deficient neurons associated with lower IP 3...
Glutamate excitotoxicity is responsible for neuronal death in acute neurological disorders including stroke, trauma and neurodegenerative disease. Loss of calcium homeostasis a key mediator glutamate-induced cell death. The neurotransmitter dopamine (DA) known to modulate signalling, here we show that it can do so response physiological concentrations glutamate. Furthermore, DA able protect neurons from at pathological We demonstrate has novel role preventing delayed deregulation cortical,...
During early development, neurons undergo complex morphological rearrangements to assemble into neuronal circuits and propagate signals. Rapid growth requires a large quantity of building materials, efficient intracellular transport also considerable amount energy. To produce this energy, the neuron should first generate new mitochondria because pre-existing are likely unable provide sufficient acceleration in ATP production. Here, we demonstrate that mitochondrial biogenesis production...
Background Parkinson's disease is a common neurodegenerative characterised by progressive loss of dopaminergic neurons, leading to dopamine depletion in the striatum. Mutations PINK1 gene cause an autosomal recessive form disease. Loss function causes mitochondrial dysfunction, increased reactive oxygen species production and calcium dysregulation, which increases susceptibility neuronal death The basis vulnerability not well understood. Methodology We investigated mechanism induced cell...
Variants in the SPATA5 gene were recently described a cohort of patients with global developmental delay, sensorineural hearing loss, seizures, cortical visual impairment and microcephaly. protein localizes predominantly mitochondria is proposed to be involved mitochondrial function brain processes. However no functional studies have been performed. This study describes five psychomotor microcephaly, epilepsy impairment, who thought clinically disease subsequent whole-exome sequencing...
<title>Abstract</title> Loss of CISD2, an iron-sulfur cluster transfer protein, results in type 2 Wolfram syndrome (WFS2), a disorder associated with severe impacts on pancreatic beta cell and neuronal functions. CISD2 has been implicated Ca2+ signaling but the molecular basis cellular consequences remain poorly understood. In this work, we demonstrate that Cisd2 intersects intracellular dynamics at different levels, including as interactor IP3Rs protein contributing to ER-mitochondrial...
During early development, neurons undergo complex morphological rearrangements to assemble into neuronal circuits and propagate signals. Rapid growth requires a large quantity of building materials, efficient intracellular transport also considerable amount energy. To produce this energy, the neuron should first generate new mitochondria because pre-existing are unlikely provide sufficient acceleration in ATP production. Here, we demonstrate that mitochondrial biogenesis production required...
Unverricht-Lundborg disease (EPM1) has been considered to be an autosomal-recessive related with loss of function mutations in the gene encoding cystatin B. Although heterozygous carriers are generally asymptomatic, earlier studies Finnish EPM1 families have reported minor symptoms together slight changes EEG recordings also near relatives patients. Here we tested hypothesis that phenotype is expressed subjects using 17-month-old B deficient mice as a model disease. Western blot analysis...
Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1) is a rare neurologic disorder, associated with mutations in Cystatin B (Cstb) gene. Mice lacking Cstb, cysteine protease inhibitor cathepsine family proteases, provide mammalian model for EPM1 by displaying similarly progressive ataxia, myoclonic seizures, and neurodegeneration. However, linkage Cstb deficit on molecular level to pathologic features like jerks or tonic-clonic seizures has remained unclear. We examined...
Summary: Purpose: To evaluate the levels of tryptophan and its metabolites along serotonin (5‐HT) kynurenine (KYN) pathways in serum progressive myoclonus epilepsy (EPM1) patients cystatin B (CSTB)‐deficient mice, a model system for EPM1. Methods: Tryptophan KYN were determined EPM1 CSTB‐deficient mice by reverse‐phase high‐pressure liquid chromatography (HPLC) with electrochemical detection. Results: Reduced 5‐HT intermediate metabolite 3‐hydroxyanthranilic acid found mice. A similar trend...
SpringerPlus 2015, 4(Suppl 1):L1 MicroRNAs (miRNAs) are short, 22-25 nucleotide long transcripts that may suppress entire signaling pathways by interacting with the 3'-untranslated region (3'-UTR) of coding mRNA targets, interrupting translation and inducing degradation these targets.The 3'-UTRs brain compared to other tissues predict important roles for miRNAs.Supporting this notion, we found miRNAs co-evolved their target transcripts, non-coding pseudogenes miRNA recognition elements...