5 documents found, page 1 of 1
Profiling microglia in a mouse model of Machado–Joseph disease
Campos, Ana Bela; Silva, Sara Duarte; Fernandes, Bruno; Neves, Sofia Pereira das; Marques, Fernanda; Castro, Andreia Teixeira; Carvalho, Andreia NevesMicroglia have been increasingly implicated in neurodegenerative diseases (NDs), and specific disease associated microglia (DAM) profiles have been defined for several of these NDs. Yet, the microglial profile in Machado–Joseph disease (MJD) remains unexplored. Here, we characterized the profile of microglia in the CMVMJD135 mouse model of MJD. This characterization was performed using primary microglial cultur...
Absence of Tau triggers age-dependent sciatic nerve morphofunctional deficits a...
Lopes, Sofia Oliveira; Lopes, André Teixeira; Pinto, Vítor Manuel Silva; Guimarães, Marco Rafael; Sardinha, Vanessa Alexandra Morais; Silva, Sara DuarteDementia is the cardinal feature of Alzheimer's disease (AD), yet the clinical symptoms of this disorder also include a marked loss of motor function. Tau abnormal hyperphosphorylation and malfunction are well-established key events in AD neuropathology but the impact of the loss of normal Tau function in neuronal degeneration and subsequent behavioral deficits is still debated. While Tau reduction has been inc...
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...
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...
Lithium chloride therapy fails to improve motor function in a transgenic mouse ...
Silva, Sara Duarte; Carvalho, Andreia Neves; Cunha, Carina Soares; Castro, Andreia Cristiana Teixeira de; Oliveira, Pedro; Fernandes, Anabela SilvaThe accumulation of misfolded proteins in neurons, leading to the formation of cytoplasmic and nuclear aggregates, is a common theme in age-related neurodegenerative diseases, possibly due to disturbances of the proteostasis and insufficient activity of cellular protein clearance pathways. Lithium is a well-known autophagy inducer that exerts neuroprotective effects in different conditions and has been proposed...