Loading...
2 results
Search Results
Now showing 1 - 2 of 2
- Mutant Ataxin-2 expression in aged animals aggravates neuropathological features associated with Spinocerebellar Ataxia type 2Publication . Afonso, Inês T.; Lima, Patrícia; Conceição, André; Matos, Carlos A; Nóbrega, ClévioSpinocerebellar ataxia type 2 (SCA2) is a rare autosomal, dominantly inherited disease, in which the affected individuals have a disease onset around their third life decade. The molecular mechanisms underlying SCA2 are not yet completely understood, for which we hypothesize that aging plays a role in SCA2 molecular pathogenesis. In this study, we performed a striatal injection of mutant ataxin-2 mediated by lentiviral vectors, in young and aged animals. Twelve weeks post-injection, we analyzed the striatum for SCA2 neuropathological features and specific aging hallmarks. Our results show that aged animals had a higher number of mutant ataxin-2 aggregates and more neuronal marker loss, compared to young animals. Apoptosis markers, cleaved caspase-3, and cresyl violet staining also indicated increased neuronal death in the aged animal group. Additionally, mRNA levels of microtubule-associated protein 1 light-chain 3B (LC3) and sequestosome-1 (SQSTM1/p62) were altered in the aged animal group, suggesting autophagic pathway dysfunction. This work provides evidence that aged animals injected with expanded ataxin-2 had aggravated SCA2 disease phenotype, suggesting that aging plays an important role in SCA2 disease onset and disease progression.
- On the role of RNA binding proteins in polyglutamine diseases: from pathogenesis to therapeuticsPublication . Conceição, André; Koppenol, Rebekah; Nóbrega, ClévioPolyglutamine (polyQ) diseases are a group of different neurodegenerative disorders characterized by an abnormal expansion of the trinucleotide cytosine-adenine-guanine (CAG) within coding regions of each disease-associated gene. The abnormal expansion translates into a protein bearing an abnormally long tract of glutamines. The expanded proteins are prone to aggregate, promote aberrant interaction with other proteins and mRNAs and contribute to cellular pathway disruption (Matos et al., 2019). To date, nine different polyQ diseases are described, including among others, Huntington’s disease, and six different spinocerebellar ataxias (SCA). Patients affected by polyQ diseases, suffer a myriad of motor symptoms that include ataxia, dysphagia, tremors, dysarthria, and even dementia. Unfortunately, there is no cure nor treatment able to delay the disease and patients rely only on symptomatic and supportive treatments culminating in premature death (Takahashi et al., 2010).