A5062748707- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- RNA modifications and cancer
- RNA Research and Splicing
- Parkinson's Disease Mechanisms and Treatments
- Autophagy in Disease and Therapy
- RNA regulation and disease
- Amyotrophic Lateral Sclerosis Research
- interferon and immune responses
- Sphingolipid Metabolism and Signaling
- Microtubule and mitosis dynamics
- Memory and Neural Mechanisms
- Nuclear Receptors and Signaling
- Neuroscience and Neuropharmacology Research
- DNA Repair Mechanisms
- Neurotransmitter Receptor Influence on Behavior
- Neurological diseases and metabolism
- Neuroscience of respiration and sleep
- Pediatric Pain Management Techniques
- Erythrocyte Function and Pathophysiology
- Biochemical effects in animals
- Endoplasmic Reticulum Stress and Disease
- Ubiquitin and proteasome pathways
- Alzheimer's disease research and treatments
- Connexins and lens biology
Goethe University Frankfurt
2017-2024
University of Calgary
2020-2024
Hospital Universitari Germans Trias i Pujol
2014-2018
Universitat Autònoma de Barcelona
2018
Universitat de Barcelona
2014
PINK1 deficiency causes the autosomal recessive PARK6 variant of Parkinson's disease. activates ubiquitin by phosphorylation and cooperates with downstream ligase PARKIN, to exert quality control autophagic degradation mitochondria misfolded proteins in all cell types. Global transcriptome profiling mouse brain neuron cultures were assessed protein-protein interaction diagrams pathway enrichment algorithms. Validation quantitative reverse transcriptase polymerase chain reaction immunoblots...
Large polyglutamine expansions in Ataxin-2 (ATXN2) cause multi-system nervous atrophy Spinocerebellar Ataxia type 2 (SCA2). Intermediate size carry a risk for selective motor neuron degeneration, known as Amyotrophic Lateral Sclerosis (ALS). Conversely, the depletion of ATXN2 prevents disease progression ALS. Although interacts directly with RNA, and ALS pathogenesis there is crucial role RNA toxicity, affected functional pathways remain ill defined. Here, we examined an authentic SCA2 mouse...
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion mutations in the ATXN2 gene, mainly affecting motor neurons spinal cord and Purkinje cerebellum. While large expansions were shown to cause SCA2, intermediate length lead increased risk for several atrophic processes including amyotrophic lateral sclerosis Parkinson variants, e.g. progressive supranuclear palsy. Intense efforts pioneer a neuroprotective therapy SCA2 require...
Abstract Background Spinocerebellar ataxia type 2 (SCA2) is a polyglutamine disorder, and variants in its disease protein Ataxin-2 act as modifiers the progression of Amyotrophic Lateral Sclerosis. There are no reliable molecular biomarkers for SCA2. Objectives The aim this study was to define novel biomarker candidates Methods Using cerebellar cervicothoracic spinal cord RNA from Atxn2 -CAG100-KnockIn wildtype mice, multi-omics conducted, followed by validation mice humans. Global...
Ataxin-2 (human gene symbol ATXN2) acts during stress responses, modulating mRNA translation and nutrient metabolism. knockout mice exhibit progressive obesity, dyslipidemia, insulin resistance. Conversely, the ATXN2 gain of function due to fact polyglutamine (polyQ) expansions leads a dominantly inherited neurodegenerative process named spinocerebellar ataxia type 2 (SCA2) with early adipose tissue loss late muscle atrophy. We tried understand lipid dysregulation in SCA2 patient brain an...
The ventrolateral periaqueductal gray (vlPAG) functionally projects to diverse brain regions, including the locus coeruleus (LC). Excitatory projections from vlPAG LC are well described, while few studies have indicated possibility of inhibitory projections. Here, we quantified relative proportion excitatory and vlPAG-LC in male female mice, found an unexpected overlapping population neurons expressing both GAD2 VGLUT2. Combined
Spinocerebellar ataxia type 2 (SCA2) is caused by polyglutamine expansion in Ataxin-2 (ATXN2). This factor binds RNA/proteins to modify metabolism after stress, and control calcium (Ca2+) homeostasis stimuli. Cerebellar ataxias corticospinal motor neuron degeneration are determined gain/loss ATXN2 function, so we aimed identify key molecules this atrophic process, as potential disease progression markers. Our Atxn2-CAG100-Knock-In mouse faithfully models features observed patients at...
Pain is the most debilitating symptom in juvenile idiopathic arthritis. As pain correlates poorly to extent of joint pathology, therapies that control inflammation are often inadequate as analgesics. We test hypothesis leads sensitisation nociceptive circuits central nervous system, which maintained by cytokine expression spinal cord. Here, transient was induced postnatal day (P)21 and P40 male Sprague-Dawley rats with a single intra-articular ankle injection complete Freund's adjuvant....
Abstract Mitochondrial dysfunction may activate innate immunity, e.g. upon abnormal handling of mitochondrial DNA in TFAM mutants or altered mitophagy. Recent reports showed that also deletion matrix peptidase ClpP mice triggers transcriptional upregulation inflammatory factors. Here, we studied ClpP-null mouse brain at two ages and embryonal fibroblasts, to identify which signaling pathways are responsible, employing mass spectrometry, subcellular fractionation, immunoblots, reverse...
Abstract Opioid withdrawal is a liability of chronic opioid use and misuse, impacting people who prescription or illicit opioids. Hyperactive autonomic output underlies many the aversive symptoms that make it difficult to discontinue use. The locus coeruleus (LC) an important centre within brain with poorly defined role in withdrawal. We show here pannexin-1 (Panx1) channels expressed on microglia critically modulate LC activity during Within LC, we found spinally projecting tyrosine...
Hereditary Parkinson's disease (PD) can be triggered by an autosomal dominant overdose of alpha-Synuclein (SNCA) as stressor or the recessive deficiency PINK1 Serine/Threonine-phosphorylation activity stress-response. We demonstrated combination PINK1-knockout with overexpression SNCAA53T in double mutant (DM) mice to exacerbate locomotor deficits and reduce lifespan. To survey posttranslational modifications proteins underlying pathology, brain hemispheres old DM underwent quantitative...
Ataxin-2 (ATXN2) acts during stress-responses, modulating mRNA translation and nutrient metabolism. Atxn2 knockout mice exhibit progressive obesity, dyslipidemia insulin resistance. Conversely, the ATXN2 gain-of-function due to polyGlutamine (polyQ) expansions leads a dominantly inherited neurodegenerative process named spinocerebellar ataxia type 2 (SCA2), with early adipose tissue loss late muscle atrophy. We tried understand lipid dysregulation in SCA2 patient brain an authentic mouse...
The autosomal recessive disorder Ataxia-Telangiectasia is caused by a dysfunction of the stress response protein, ATM. In nucleus proliferating cells, ATM senses DNA double-strand breaks and coordinates their repair. This role explains T-cell tumour risk. However, it remains unclear whether this function relevant for postmitotic neurons underlies cerebellar atrophy, since cytoplasmic in neurons. Here, we used ATM-null mice that survived early immune deficits via bone-marrow transplantation,...
As cystatin C (CysC) is involved in some forms of neurodegeneration, we investigated the possible relationship between CysC and multiple system atrophy (MSA), including its parkinsonian (MSAp) cerebellar (MSAc) phenotypes.Cystatin gene (CST3) haplotypes were determined by PCR followed KspI digestion 50 MSA patients 108 controls. CST3 cathepsins B, D L1 mRNA levels studied frozen post-mortem caudate nucleus samples eight MSAp, four MSAc 18 control brains analysed ΔΔCt method....
The autosomal recessive disorder Ataxia-Telangiectasia is caused by dysfunction of the stress response protein ATM. In nucleus proliferating cells, ATM senses DNA double-strand breaks and coordinates their repair. This role explains T-cell tumor risk. However, it remains unclear whether this function relevant for postmitotic neurons underlies cerebellar atrophy, since cytoplasmic in neurons. Here, we used ATM-null mice that survived early immune deficits bone-marrow transplantation, reached...
Lewy body diseases (LBD) include Parkinson’s disease (PD) and dementia with bodies (DLB) together Alzheimer’s (AD) they show an important neuropathological clinical overlap. The human alpha- beta-synuclein genes (SNCA SNCB) are key factors for the development of diseases. Here, we aimed to analyze genotype distribution potentially functional SNPs in SNCA SNCB, perform haplotype analysis identify insertion deletion (INDEL) variations within regulatory region SNCB which might be responsible...
Hereditary Parkinson’s disease (PD) can be triggered by an autosomal dominant overdose of alpha-Synuclein (SNCA) as stressor or the recessive deficiency PINK1 Serine/Threonine-phosphorylation activity stress-response. We demonstrated combination PINK1-knockout with overexpression SNCAA53T in double mutant (DM) mice to exacerbate locomotor deficits and reduce lifespan. To survey posttranslational modifications proteins underlying pathology, brain hemispheres old DM underwent...
Spinocerebellar ataxia type 2 (SCA2) is caused by polyglutamine expansion in Ataxin-2 (ATXN2). This factor binds RNA/proteins to modify metabolism after stress, and control calcium (Ca2+) homeostasis stimuli, thus exerting crucial neuroprotection for cerebellar ataxias corticospinal motor neuron degeneration. Our Atxn2-CAG100-Knock-In mouse faithfully models features observed patients at pre-onset, early terminal stages. Here, its global RNA profiling revealed downregulation of signaling...
Abstract Toxic polyglutamine (polyQ) expansions in ATXN2 trigger neurodegenerative processes, causing Spinocerebellar Ataxia type 2 (SCA2), and enhancing TDP-43-dependent pathology Amyotrophic Lateral Sclerosis (ALS) / Fronto-Temporal Dementia (FTD). Primary disease events can be compensated transiently, delaying manifestation. To define potential therapy targets, we documented how cells modify their phospho-signals the interactome changes, using preferentially affected nervous tissues from...
Abstract Large polyglutamine expansions in Ataxin-2 (ATXN2) cause multi-system nervous atrophy Spinocerebellar Ataxia type 2 (SCA2). Intermediate size carry a risk for selective motor neuron degeneration, known as Amyotrophic Lateral Sclerosis (ALS). Conversely, the depletion of ATXN2 prevents disease progression ALS. Although interacts directly with RNA, and ALS pathogenesis there is crucial role RNA toxicity, affected functional pathways remain ill defined. Here, we examined an authentic...
Transcript changes of Pink1-deficient mouse cerebellar tissue at the age 18 months in qPCR analyses represented bar graphs. (A) Significant downregulation Srsf10 mRNA and upregulations Creb3 Nfkbia mRNAs confirm alteration within spliceosomal, ER stress neuroinflammation pathways. The significant dysregulation a Ube3a splice isoform is particularly interesting as potential target spliceosome alterations view its role degradation alpha-synuclein. scheme exon intron structure with location...