4 documents found, page 1 of 1
Aripiprazole offsets mutant ATXN3-induced motor dysfunction by targeting dopami...
Jalles, Ana; Vieira, Cármen Maria Leal; Pereira-Sousa, Joana; Campos, Daniela Vilasboas; Mota, Ana Francisca; Vasconcelos, SaraThe atypical antipsychotic aripiprazole is a Food and Drug Administration-approved drug for the treatment of psychotic, mood, and other psychiatric disorders. Previous drug discovery efforts pinpointed aripiprazole as an effective suppressor of Machado–Joseph disease (MJD) pathogenesis, as its administration resulted in a reduced abundance and aggregation of mutant Ataxin-3 (ATXN3) proteins. Dopamine partial ag...
The disruption of proteostasis in neurodegenerative diseases
Jalles, Ana; Maciel, P.Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegene...
Therapeutic strategies for polyQ diseases: from cellular and animal models to t...
Silva, Sara Carina Duarte; Jalles, Ana; Maciel, P.Polyglutamine (PolyQ) diseases are a group of neurodegenerative disorders caused by the expansion of an unstable CAG trinucleotide repeat within the coding region of several otherwise unrelated genes. This expansion encodes an abnormally long polyQ tract that which, above a threshold size, leads to misfolding and aggregation, eventually resulting in neurodegeneration. These disorders all share key features incl...
Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the ...
Castro, Andreia Cristiana Teixeira de; Ailion, Michael; Jalles, Ana; Brignull, Heather; Vilaça, João L.; Dias, N. S.; Rodrigues, Pedro L.The risk of developing neurodegenerative diseases increases with age. Although many of the molecular pathways regulating proteotoxic stress and longevity are well characterized, their contribution to disease susceptibility remains unclear. In this study, we describe a new Caenorhabditis elegans model of Machado–Joseph disease pathogenesis. Pan-neuronal expression of mutant ATXN3 leads to a polyQ-length dependen...