A5059252386- Genetic Neurodegenerative Diseases
- Genetics and Neurodevelopmental Disorders
- Mitochondrial Function and Pathology
- Cellular Mechanics and Interactions
- Neurogenesis and neuroplasticity mechanisms
- RNA Research and Splicing
- Nerve injury and regeneration
- Axon Guidance and Neuronal Signaling
- Autism Spectrum Disorder Research
- RNA regulation and disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Genomic variations and chromosomal abnormalities
- Neuroscience and Neural Engineering
- Neuroscience and Neuropharmacology Research
- 3D Printing in Biomedical Research
- DNA Repair Mechanisms
- Amyotrophic Lateral Sclerosis Research
- Caveolin-1 and cellular processes
- Neurological disorders and treatments
- Neurological diseases and metabolism
- Parathyroid Disorders and Treatments
- RNA modifications and cancer
- Skin and Cellular Biology Research
- Radiomics and Machine Learning in Medical Imaging
- Amyloidosis: Diagnosis, Treatment, Outcomes
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto
2017-2024
Universidade do Porto
2005-2023
Instituto de Biologia Molecular e Celular
2011-2019
Johns Hopkins University
2005-2015
Johns Hopkins Medicine
2005-2015
Spinocerebellar ataxia 36 has been recently described in Japanese families as a new type of spinocerebellar with motor neuron signs. It is caused by GGCCTG repeat expansion intron 1 NOP56. Family interview and document research allowed us to reconstruct two extensive, multigenerational kindreds stemming from the same village (Costa da Morte Galicia, Spain), 17th century. We found presence mutation co-segregating disease these whom we had previously identified an ∼0.8 Mb linkage region...
Huntington disease-like 2 (HDL2) is a progressive, late onset autosomal dominant neurodegenerative disorder, with remarkable similarities to disease (HD). HDL2 caused by CTG/CAG repeat expansion. In the CTG orientation, located within alternatively spliced exon 2A of junctophilin-3 (JPH3), potentially encoding polyleucine and polyalanine, whereas on strand antisense JPH3, in frame encode polyglutamine. The JPH3 protein product serves stabilize junctional membrane complexes regulate neuronal...
ABSTRACT Objective SCA12 is a progressive autosomal‐dominant disorder, caused by CAG/CTG repeat expansion in PPP2R2B on chromosome 5q32, and characterized tremor, gait ataxia, hyperreflexia, dysmetria, abnormal eye movements, anxiety, depression, sometimes cognitive impairment. Neuroimaging has demonstrated cerebellar cortical atrophy. We now present the neuropathology of first autopsied brain utilize cell models to characterize potential mechanisms neurodegeneration. Methods A fixed was...
Abstract During central nervous system development, oligodendrocytes form structurally and functionally distinct actin‐rich protrusions that contact wrap around axons to assemble myelin sheaths. Establishment of axonal is a limiting step in myelination relies on the oligodendrocyte's ability locally coordinate cytoskeletal rearrangements with production, under control transcriptional differentiation program. The molecules provide fine‐tuning actin dynamics during oligodendrocyte axon...
Abstract Microfluidics devices for co-culturing neurons and oligodendrocytes represent an important in vitro research tool to decipher myelination mechanisms health disease the identification of novel treatments myelin diseases. In reported using primary rodent cells, spontaneous formation sheaths has been challenging random orientation neurites impede analysis myelination. Furthermore, fabrication methods show limitations, highlighting need cell-based models. present study, we describe a...
Myelin improves axonal conduction velocity and is essential for nerve development regeneration. In peripheral nerves, Schwann cells depend on bidirectional mechanical biochemical signaling to form the myelin sheath but mechanism underlying this process not understood. Rho GTPases are integrators of "outside-in" that link cytoskeletal dynamics with cellular architecture regulate morphology adhesion. Using cell-specific gene inactivation in mouse, we discovered RhoA promotes initiation...
Abstract Timely differentiation and myelin formation by oligodendrocytes are essential for the physiological functioning of central nervous system (CNS). While Rho GTPase RhoA has been hinted as a negative regulator sheath formation, precise in vivo mechanisms have remained elusive. Here we show that controls timing progression myelination through fine‐tuned balance between cortical tension, membrane tension cell shape. Using conditional mouse model, observe Rhoa ablation results...
Transthyretin Amyloid Polyneuropathy (ATTR-PN) is characterized by the deposition of amyloidogenic TTR, particularly in dorsal root ganglia (DRG) and peripheral nerve axons, resulting sensory axonopathy. Here, we investigated role cytoskeleton alterations axons from an ATTR-PN mouse model searched for genetic modifiers human patient samples. We employed hTTRA97S knock-in to examine cellular molecular changes axons. Our approach combined proteomic analysis sural nerve, live imaging...
Abstract The fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by expansions of 55-200 CGG repeats in the 5'UTR FMR1 gene. These premutation have relatively high frequency general population. To estimate premutations among Portuguese males with non-familial, movement disorders unknown etiology, we assessed repeat size disease onset after age 50 and negative or family history for disorders, who were sent SCA, HD, PD genetic testing at...
Abstract Spinocerebellar ataxia type 8 (SCA8) is an autosomal dominant late‐onset neurodegenerative disorder, belonging to the group of diseases caused by trinucleotide repeat expansions. SCA8 remains one most intriguing SCAs, regarding reduced disease penetrance, and high instability poorly understood functional meaning (CTA) n (CTG) expansion. We performed haplotype sequencing analysis in a large region, encompassing repeat, four 20 control Portuguese families. The results from study...
Abstract Loss of myelin underlies the pathology several neurological disorders diverse etiology. CNS remyelination by adult oligodendrocyte progenitor cells (OPCs) can occur but it differs from developmental myelination carried out neonatal OPCs. We asked whether proteome remyelinated regions is changed. compared formed during development to attained after lysolecithin-induced demyelination in mouse spinal cord. Mass-spectrometry analysis iTRAQ labelled protein lysates showed that different...
Bidirectional transmission of mechanical and biochemical signals is integral to cell-environment communication underlies the function Schwann cells, myelinating glia peripheral nervous system. As major integrators “outside-in” signaling, Rho GTPases link actin cytoskeleton dynamics with cellular architecture regulate adhesion cell deformation. Using cell-specific gene inactivation, we discovered that RhoA promotes initiation myelination, axonal wrapping axial spreading later required...