17 documents found, page 1 of 2
Molecular hallmarks of neurodegeneration in polyglutamine spinocerebellar ataxias
Nóbrega, Clévio; Marcelo, Adriana; Vieira da Conceição, André Filipe; Encarnação Estevam, Bernardo Alexandre; Rajado, Ana TeresaPolyglutamine spinocerebellar ataxias (PolyQ SCAs) comprise a group of six inherited rare neurodegenerative diseases. They are caused by abnormal mutation of a CAG tract in six otherwise unrelated genes, leading to a complex cascade of molecular events that culminate in neuronal death. Based on decades of research in these diseases, this review identifies and categorizes the distinctive hallmarks involved in th...
The stress granule protein G3BP1 alleviates spinocerebellar ataxia-associated d...
Koppenol, Rebekah; Conceição, André; Afonso, Inês T.; Afonso-Reis, Ricardo; Costa, Rafael G.; Tomé, Sandra; Teixeira, Diogo; da Silva, Joana PintoPolyglutamine diseases are a group of neurodegenerative disorders caused by an abnormal expansion of CAG repeat tracts in the codifying regions of nine, otherwise unrelated, genes. While the protein products of these genes are suggested to play diverse cellular roles, the pathogenic mutant proteins bearing an expanded polyglutamine sequence share a tendency to self-assemble, aggregate and engage in abnormal mol...
The stress granule protein G3BP1 alleviates spinocerebellar ataxia-associated d...
Koppenol, Rebekah; Conceição, André; Afonso, Inês T.; Afonso-Reis, Ricardo; Costa, Rafael G; Tomé, Sandra; Teixeira, Diogo; Pinto-da-Silva, JoanaKoppenol et al. show that overexpression of G3BP1 in cell models of SCA2 and SCA3 leads to a reduction in ataxin-2 and ataxin-3 aggregation. G3BP1 lentiviral delivery reduces motor deficits and neuropathology in preclinical models, suggesting that G3BP1 may be a potential therapeutic target for polyQ disorders. Polyglutamine diseases are a group of neurodegenerative disorders caused by an abnormal expansion of ...
Autophagy in Spinocerebellar ataxia type 2, a dysregulated pathway, and a targe...
Marcelo, Adriana; Afonso, Inês T.; Afonso-Reis, Ricardo; Brito, David V. C.; Costa, Rafael G.; Rosa, Ana; Alves-Cruzeiro, João; Ferreira, BeneditaSpinocerebellar ataxia type 2 (SCA2) is an incurable and genetic neurodegenerative disorder. The disease is characterized by progressive degeneration of several brain regions, resulting in severe motor and non-motor clinical manifestations. The mutation causing SCA2 disease is an abnormal expansion of CAG trinucleotide repeats in the ATXN2 gene, leading to a toxic expanded polyglutamine segment in the translate...
Stress granules, RNA-binding proteins and polyglutamine diseases: too much aggr...
Marcelo, Adriana; Koppenol, Rebekah; Almeida, Luís Pereira de; Matos, Carlos A.; Nóbrega, ClévioStress granules (SGs) are membraneless cell compartments formed in response to different stress stimuli, wherein translation factors, mRNAs, RNA-binding proteins (RBPs) and other proteins coalesce together. SGs assembly is crucial for cell survival, since SGs are implicated in the regulation of translation, mRNA storage and stabilization and cell signalling, during stress. One defining feature of SGs is their d...
Stress granules, RNA-binding proteins and polyglutamine diseases: too much aggr...
Marcelo, Adriana; Koppenol, Rebekah; Almeida, Luis Pedro; Matos, Carlos A; Nóbrega, ClévioStress granules (SGs) are membraneless cell compartments formed in response to different stress stimuli, wherein translation factors, mRNAs, RNA-binding proteins (RBPs) and other proteins coalesce together. SGs assembly is crucial for cell survival, since SGs are implicated in the regulation of translation, mRNA storage and stabilization and cell signalling, during stress. One defining feature of SGs is their d...
Autophagy in Spinocerebellar ataxia type 2, a dysregulated pathway, and a targe...
Marcelo, Adriana; Afonso, Inês T.; Afonso-Reis, Ricardo; Brito, David V. C.; Costa, Rafael G.; Rosa, Ana; Alves-Cruzeiro, João; Ferreira, BeneditaSpinocerebellar ataxia type 2 (SCA2) is an incurable and genetic neurodegenerative disorder. The disease is characterized by progressive degeneration of several brain regions, resulting in severe motor and non-motor clinical manifestations. The mutation causing SCA2 disease is an abnormal expansion of CAG trinucleotide repeats in the ATXN2 gene, leading to a toxic expanded polyglutamine segment in the translate...
The cholesterol 24-hydroxylase activates autophagy and decreases mutant hunting...
Nóbrega, Clévio; Conceição, André Francisco da; Costa, Rafael G; Koppenol, Rebekah; Sequeira, Raquel L; Nunes, Ricardo; Carmo-Silva, SaraObjective: Compromised brain cholesterol turnover and altered regulation of brain cholesterol metabolism have been allied with some neurodegenerative diseases, including Huntington’s disease (HD). Following our previous studies in HD, in this study we aim to investigate in vitro in a neuroblastoma cellular model of HD, the effect of CYP46A1 overexpression, an essential enzyme in cholesterol metabolism, on hunti...
Mesenchymal Stromal Cells' Therapy for Polyglutamine Disorders: Where Do We Sta...
Barros, Inês; Marcelo, Adriana; Silva, Teresa P.; Barata, João; Ramos, António David Rufino; Almeida, Luís P. de; Miranda, Catarina O.Polyglutamine (polyQ) diseases are a group of inherited neurodegenerative disorders caused by the expansion of the cytosine-adenine-guanine (CAG) repeat. This mutation encodes extended glutamine (Q) tract in the disease protein, resulting in the alteration of its conformation/physiological role and in the formation of toxic fragments/aggregates of the protein. This group of heterogeneous disorders shares common...
CYP46A1- gene therapy improves Machado-Joseph disease in mouse models
Nóbrega, Clévio; Mendonca, L. S.; Marcelo, Adriana; Lamaziere, A.; Tome, S.; Despres, G.; Matos, C.; Mechmet, Fatich; Langui, D.; den Dunnen, W.Aims/Context: Machado-Joseph Disease (MJD) is a neurodegenerative disease associated with extensive neuronal death. Defects in brain cholesterol metabolism may contribute to neurodegenerative diseases.