A5030974445- Parkinson's Disease Mechanisms and Treatments
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Nuclear Receptors and Signaling
- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Nerve injury and regeneration
- Cell Image Analysis Techniques
- RNA regulation and disease
- Alzheimer's disease research and treatments
- Protein Hydrolysis and Bioactive Peptides
- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Synthesis and biological activity
- Coastal wetland ecosystem dynamics
- Genetic Neurodegenerative Diseases
- Medical and Biological Sciences
- Autophagy in Disease and Therapy
- Genetics and Neurodevelopmental Disorders
- Mitochondrial Function and Pathology
- Seedling growth and survival studies
- Phytochemical compounds biological activities
- Connective tissue disorders research
- Virus-based gene therapy research
- Synthesis of Organic Compounds
Lund University
2015-2022
University of Lisbon
2016
University of Aveiro
2014
In this study, we sought evidence for alpha-synuclein (ASYN) expression in oligodendrocytes, as a possible endogenous source of ASYN to explain its presence glial inclusions found multiple system atrophy (MSA) and Parkinson's disease (PD). We identified oligodendrocyte lineage progenitors isolated from the rodent brain, oligodendrocytes generated embryonic stem cells, induced pluripotent cells produced fibroblasts healthy individual patients diagnosed with MSA or PD, cultures vitro. Notably,...
Induced pluripotent stem cells (iPSCs) are becoming an important source of pre-clinical models for research focusing on neurodegeneration. They offer the possibility better understanding common and divergent pathogenic mechanisms brain diseases. Moreover, iPSCs provide a unique opportunity to develop personalized therapeutic strategies, as well explore early mechanisms, since they rely use patients' own that otherwise accessible only post-mortem, when neuronal death-related cellular pathways...
The protein parkin, encoded by the PARK2 gene, is vital for mitochondrial homeostasis, and although it has been implicated in Parkinson's disease (PD), mechanisms remain unclear. We have applied mass spectrometry-based proteomics to investigate effects of parkin dysfunction on proteome human isogenic induced pluripotent stem cell (iPSC)-derived neurons with without knockout (KO). proteomic analysis quantified nearly 60% all proteins, 119 which were dysregulated KO. changes indicated...
Here, we examine the cellular changes triggered by tumor necrosis factor alpha (TNF-α) and different alpha-synuclein (αSYN) species in astrocytes derived from induced pluripotent stem cells. Human treated with TNF-α display a strong reactive pro-inflammatory phenotype upregulation of gene networks, activation nuclear κB (NF-κB) pathway, release cytokines, whereas those high-molecular-weight αSYN fibrils acquire antigen (cross)-presenting major histocompatibility complex (MHC) genes increased...
SignificanceOur results demonstrate the existence of early cellular pathways and network alterations in oligodendrocytes alpha-synucleinopathies Parkinson's disease multiple system atrophy. They further reveal involvement an immune component triggered by alpha-synuclein protein, as well a connection between (epi)genetic changes reactivity The knowledge generated this study could be used to devise novel therapeutic approaches treat synucleinopathies.
Abstract Variations in the POLG1 gene encoding catalytic subunit of mitochondrial DNA polymerase gamma, have recently been associated with Parkinson’s disease (PD), especially patients diagnosed progressive external ophthalmoplegia (PEO). However, majority studies reporting this association mainly focused on genetic identification variation PD patient primary cells, and determination copy number, providing little information about cellular alterations existing brain particular dopaminergic...
Oligodendrocytes are part of the glial cells located in central nervous system, capable providing trophic support to neurons and ensheathing their axons. These can become dysfunctional under pathologic condition. Rodent human pluripotent stem inexhaustible sources for producing oligodendrocytes that be used disease modeling cell replacement therapy studies. They also offer many opportunities model contribution non-genetic disorders such as multiple system atrophy. In this method article, we...
Mouse embryonic stem cell (mESC) lines were derived by crossing heterozygous transgenic (tg) mice expressing green fluorescent protein (GFP) under the control of rat tyrosine hydroxylase (TH) promoter, with homozygous alpha-synuclein (aSYN) human mutant SNCAA53T mouse Prion promoter (MoPrP), or wildtype (WT) mice. The expression GFP and aSYN was validated immunocytochemistry in midbrain neuron cultures upon differentiation mESC using stromal cell-derived inducing activity. These can help to...
Mutations in the glucocerebrosidase (GBA) gene have been associated with development of Parkinson's disease (PD). An induced pluripotent stem cell (iPSC) line was generated from a 60-year old patient diagnosed PD and carrying new mutation variant p.R301C GBA. Using non-integrating Sendai virus-based technology, we utilized OCT3/4, SOX2, c-MYC KLF4 transcription factors to reprogram skin fibroblasts into iPSCs. The iPSC retained mutation, displayed expression common pluripotency markers,...
Here, we describe the generation of an induced pluripotent stem cell (iPSC) line, from a male patient diagnosed with Parkinson's disease (PD). The carries heterozygous variation p.A53T in SNCA gene. Skin fibroblasts were reprogrammed using non-integrating Sendai virus technology to deliver OCT3/4, SOX2, c-MYC and KLF4 factors. generated iPSC line (CSC-32) preserved mutation, displayed expression common pluripotency markers, differentiated into derivatives three germ layers, exhibited normal...