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Cerebral malaria model applying human brain organoids

Pedrosa, Ana Rita Silva; Campos, Jonas Oliveira; Fernandes, Aline Marie; Silva, Miguel; Calçada, Carla Sofia Martins; Marote, Ana Maria Franco Aveiro

Neural injuries in cerebral malaria patients are a significant cause of morbidity and mortality. Nevertheless, a comprehensive research approach to study this issue is lacking, so herein we propose an in vitro system to study human cerebral malaria using cellular approaches. Our first goal was to establish a cellular system to identify the molecular alterations in human brain vasculature cells that resemble the...


Unilateral intrastriatal 6-hydroxydopamine lesion in mice: a closer look into n...

Pinheiro, Bárbara Filipa Mendes; Cunha, Carina Isabel Soares; Marote, Ana Maria Franco Aveiro; Loureiro-Campos, Eduardo; Campos, Jonas Oliveira

Parkinson’s disease (PD) is a prevalent movement disorder characterized by the progressive loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). The 6-hydroxydopamine (6-OHDA) lesion is still one of the most widely used techniques for modeling Parkinson’s disease (PD) in rodents. Despite commonly used in rats, it can be challenging to reproduce a similar lesion in mice. Moreover, there is a lac...


Unveiling the potential of iPSCs-derived mesenchymal stem cells for the develop...

Marote, Ana Maria Franco Aveiro

A doença de Parkinson (DP) é a segunda doença neurodegenerativa mais comum mundialmente, caracterizada principalmente pela perda de neurónios dopaminérgicos na substancia nigra pars compacta (SNc), levando a uma desnervação do sistema nigroestriatal. A neurodegeneração na SNc e noutras áreas dopaminérgicas e não dopaminérgicas são clinicamente traduzidas em lentidão dos movimentos, rigidez e tremor em repouso, ...


Extremely low frequency magnetic field induces human neuronal differentiation t...

Özgün, Alp; Marote, Ana Maria Franco Aveiro; Behie, Leo A.; Salgado, A.; Garipcan, Bora

Magnetic fields with different frequency and intensity parameters exhibit a wide range of effects on different biological models. Extremely low frequency magnetic field (ELF MF) exposure is known to augment or even initiate neuronal differentiation in several in vitro and in vivo models. This effect holds potential for clinical translation into treatment of neurodegenerative conditions such as autism, Parkinson...


Bone marrow mesenchymal stem cells' secretome exerts neuroprotective effects in...

Pinheiro, Bárbara Filipa Mendes; Anjo, Sandra I.; Manadas, Bruno; da Silva, Jorge D.; Marote, Ana Maria Franco Aveiro; Behie, Leo A.; Teixeira, Fábio G.

Parkinson's disease (PD) is characterized by a selective loss of dopamine (DA) neurons in the human midbrain causing motor dysfunctions. The exact mechanism behind dopaminergic cell death is still not completely understood and, so far, no cure or neuroprotective treatment for PD is available. Recent studies have brought attention to the variety of bioactive molecules produced by mesenchymal stem cells (MSCs), g...


Generation of a human induced pluripotent stem cell line (CSC-42) from a patien...

Savchenko, Ekaterina; Marote, Ana Maria Franco Aveiro; Russ, Kaspar; Collin, Anna; Goldwurm, Stefano; Roybon, Laurent; Pomeshchik, Yuriy

Skin fibroblasts were collected from a 44-year-old patient with sporadic case of Parkinson's disease (PD). The non-integrating Sendai virus vector encoding OCT3/4, SOX2, c-MYC and KLF4 was used to reprogram fibroblasts into induced pluripotent stem cells (iPSCs). Generated iPSCs had normal karyotypes, expressed common stem cell markers, and were capable of differentiating into all three germ layers. Generated l...


Generation of an integration-free induced pluripotent stem cell line (CSC-43) f...

Marote, Ana Maria Franco Aveiro; Pomeshchik, Yuriy; Goldwurm, Stefano; Collin, Anna; Lamas, Nuno J.; Pinto, Luísa; Salgado, A. J.; Roybon, Laurent

An induced pluripotent stem cell (iPSC) line was generated from a 36-year-old patient with sporadic Parkinson's disease (PD). Skin fibroblasts were reprogrammed using the non-integrating Sendai virus technology to deliver OCT3/4, SOX2, c-MYC and KLF4 factors. The generated cell line (CSC-43) exhibits expression of common pluripotency markers, in vitro differentiation into three germ layers and normal karyotype....


Generation of an induced pluripotent stem cell line (CSC-44) from a Parkinson's...

Marote, Ana Maria Franco Aveiro; Pomeshchik, Yuriy; Goldwurm, Stefano; Collin, Anna; Lamas, Nuno Jorge; Pinto, Luísa; Salgado, A. J.; Roybon, Laurent

Mutations in the PARK2 gene, which encodes PARKIN, are the most frequent cause of autosomal recessive Parkinson's disease (PD). We report the generation of an induced pluripotent stem cell (iPSC) line from a 78-year-old patient carrying a compound heterozygous mutation (c.823C>T and EX6del) in the PARK2 gene. Skin fibroblasts were reprogrammed using the non-integrating Sendai virus technology to deliver OCT3/4,...


Cell secretome based approaches in Parkinson's disease regenerative medicine

Marques, Cláudia R.; Marote, Ana Maria Franco Aveiro; Pinheiro, Bárbara Filipa Mendes; Teixeira, Fábio Gabriel Rodrigues; Salgado, A. J.

The available therapeutic strategies for Parkinson's disease (PD) rely only on the amelioration of the symptomatology of the disease, lacking neuroprotection or neuroregeneration capacities. Therefore, the development of disease modifying strategies is extremely important for the management of PD in the long term. Areas covered: In this review, the authors provide an overview of the current therapeutic approach...


Generation of a human induced pluripotent stem cell line (CSC-40) from a Parkin...

Russ, Kaspar; Marote, Ana Maria Franco Aveiro; Savchenko, Ekaterina; Collin, Anna; Goldwurm, Stefano; Pomeshchik, Yuriy; Roybon, Laurent

Parkinson's disease (PD) is a neurodegenerative disease with unknown etiology. Here we show the generation of an induced pluripotent stem cell (iPSC) line, named CSC-40, from dermal fibroblasts obtained from a 59-year-old male patient with a homozygous p.Q456X mutation in the PTEN-induced putative kinase 1 (PINK/PARK6) gene and a confirmed diagnosis of PD, which could be used to model familial PD. A non-integra...


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