16 documents found, page 1 of 2
Reconsidering frailty from a human and social sciences stand point: towards an ...
Sabot, Philippe; Di Martino, Carla; Moroni, Christine; Aluffi Pentini, Anna; Pabjan, Barbara; Machado, Maria Manuela Pereira; Katkoniene, AgataAlthough frailty is an important,well characterized concept in the provision of medical care to older adults,it has not been linked to the concept of vulnerability developed in the humanities and social sciences. Here, we distinguish between the two main dimensions of vulnerability: a fundamental, anthropological dimension in which people are exposed to a risk of injury, and a relational dimension in which peop...
Neuroprotective effects of creatine in the CMVMJD135 mouse model of Spinocerebe...
Silva, Sara Carina Duarte; Carvalho, Andreia Alexandra Neves; Cunha, Carina Isabel Soares; Silva, Joana M.; Castro, Andreia Cristiana TeixeiraBackground and Objective: Mitochondrial dysfunction has been implicated in several neurodegenerative diseases. Creatine administration increases concentration of the energy buffer phosphocreatine, exerting protective effects in the brain. We evaluate whether a creatine‐enriched diet would be beneficial for a mouse model of spinocerebellar ataxia type 3, a genetically defined neurodegenerative disease for which ...
Combined therapy with m-TOR-dependent and -independent autophagy inducers cause...
Silva, Sara Carina Duarte; Fernandes, Anabela Silva; Carvalho, Andreia Alexandra Neves; Cunha, Carina Isabel Soares; Castro, Andreia Cristiana TeixeiraA major pathological hallmark in several neurodegenerative disorders, like polyglutamine disorders (polyQ), including Machado-Joseph disease (MJD), is the formation of protein aggregates. MJD is caused by a CAG repeat expansion in the ATXN3 gene, resulting in an abnormal protein, which is prone to misfolding and forms cytoplasmic and nuclear aggregates within neurons, ultimately inducing neurodegeneration. Trea...
Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leadi...
Vieira, José Pedro; Lopes, Fátima Daniela Teixeira; Fernandes, Anabela Silva; Sousa, Maria Vânia; Moura, Sofia; Sousa, Susana; Costa, Bruno M.Rett syndrome is a neurodevelopmental disorder caused by mutations in the MECP2 gene. We investigated the genetic basis of disease in a female patient with a Rett-like clinical. Karyotype analysis revealed a pericentric inversion in the X chromosome -46,X,inv(X)(p22.1q28), with breakpoints in the cytobands where the MECP2 and CDKL5 genes are located. FISH analysis revealed that the MECP2 gene is not dislocated ...
Dominant negative effect of polyglutamine expansion perturbs normal function of...
Carvalho, Andreia Alexandra Neves; Logarinho, Elsa; Freitas, Ana; Silva, Sara Duarte; Costa, Maria do Carmo; Fernandes, Anabela SilvaThe physiological function of Ataxin-3 (ATXN3), a deubiquitylase (DUB) involved in Machado–Joseph Disease (MJD), remains elusive. In this study, we demonstrate that ATXN3 is required for neuronal differentiation and for normal cell morphology, cytoskeletal organization, proliferation and survival of SH-SY5Y and PC12 cells. This cellular phenotype is associated with increased proteasomal degradation of a5 integr...
Differential mtDNA damage patterns in a transgenic mouse model of Machado-Josep...
Ramos, Amanda; Kazachkova, Nadiya; Silva, Francisca; Maciel, P.; Fernandes, Anabela Silva; Silva, Sara Carina Duarte; Santos, Cristina; Lima, ManuelaMitochondrial dysfunction has been associated with late onset neurodegenerative disorders, among which is Machado-Joseph disease (MJD/SCA3). In a previous study, using a transgenic mouse model of MJD, we reported a decrease in mitochondrial DNA (mtDNA) copy number and an accumulation of the 3876-bp deletion with age and with phenotype development. We extended this study by analyzing the pattern of mtDNA depleti...
Limited effect of chronic valproic acid treatment in a mouse model of Machado-J...
Esteves, Sofia; Silva, Sara Carina Duarte; Naia, Luana; Carvalho, Andreia Alexandra Neves; Castro, Andreia Cristiana Teixeira; Rego, Ana CristinaMachado-Joseph disease (MJD) is an inherited neurodegenerative disease, caused by a CAG repeat expansion within the coding region of ATXN3 gene, and which currently lacks effective treatment. In this work we tested the therapeutic efficacy of chronic treatment with valproic acid (VPA) (200mg/kg), a compound with known neuroprotection activity, and previously shown to be effective in cell, fly and nematode model...
Serotonergic signalling suppresses ataxin 3 aggregation and neurotoxicity in an...
Castro, Andreia Cristiana Teixeira; Sousa, Ana Luísa Jales Monteiro; Esteves, Sofia; Santos, Liliana da Silva; Fernandes, Anabela SilvaPolyglutamine diseases are a class of dominantly inherited neurodegenerative disorders for which there is no effective treatment. Here we provide evidence that activation of serotonergic signalling is beneficial in animal models of Machado-Joseph disease. We identified citalopram, a selective serotonin reuptake inhibitor, in a small molecule screen of FDA-approved drugs that rescued neuronal dysfunction and red...
Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA d...
Gao, Rui; Liu, Yongping; Fernandes, Anabela Silva; Fang, Xiang; Paulucci- Holthauzen, Adriana; Chatterjee, Arpita; Zhang, Hang L.; Matsuura, TohruSpinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an untreatable autosomal dominant neurodegenerative disease, and the most common such inherited ataxia worldwide. The mutation in SCA3 is the expansion of a polymorphic CAG tri-nucleotide repeat sequence in the C-terminal coding region of the ATXN3 gene at chromosomal locus 14q32.1. The mutant ATXN3 protein encoding expanded gl...
Chronic treatment with 17-DMAG improves balance and coordination in a new mouse...
Fernandes, Anabela Silva; Silva, Sara Duarte; Carvalho, Andreia Neves; Amorim, Marina; Cunha, Carina Soares; Oliveira, Pedro; Thirstrup, KennethMachado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease currently with no treatment. We describe a novel mouse model of MJD which expresses mutant human ataxin-3 at near endogenous levels and manifests MJD-like motor symptoms that appear gradually and progress over time. CMVMJD135 mice show ataxin-3 intranuclear inclusions in the CNS and neurodegenerative changes in k...