Neuroscience, Biochemistry, Genetics and Molecular Biology
3
Scopus Publications
27
Scholar Citations
2
Scholar h-index
2
Scholar i10-index
Scopus Publications
Therapeutic Effects of Hemerocallis citrina Baroni Extract on Animal Models of Neurodegenerative Diseases Through Serotonin and HLH-30/TFEB-Dependent Mechanisms Jorge H. Fernandes, Marta Daniela Costa, Daniela Vilasboas-Campos, Bruna Ferreira-Lomba, Joana Pereira-Sousa, et al. International Journal of Molecular Sciences, 2025 Hemerocallis citrina is an herbaceous perennial plant used in Asian cuisine and Traditional Chinese Medicine. Here, we tested the therapeutic potential of extracts (HCE30%, HCE50%, and HCN) in vivo, using models of two human genetic neurodegenerative diseases—Machado–Joseph Disease/Spinocerebellar Ataxia type 3 (MJD/SCA3) and Frontotemporal Dementia with Parkinsonism associated to chromosome 17 (FTDP-17). Chronic treatment with HCE30% extract ameliorated the motor deficits typically observed in these models. Interestingly, we found that the effect on the motor phenotype of the MJD/SCA3 model was dependent on serotonergic signaling and on the action of the HLH-30/TFEB transcription factor, known to regulate the cellular response to amino acid starvation, the autophagy and mitophagy pathways, lysosome localization and biogenesis, exocytosis, and mitochondrial biogenesis. Altogether, our findings reinforce the idea that phytochemicals act through the modulation of serotonergic neurotransmission and introduce a novel layer to the HLH-30/TFEB regulatory network. Thus, it also strengthens the use of these pathways as therapeutic targets for protein-related neurodegenerative disorders and confirms the utility of medicinal plants as a source of innovation in the quest for new therapeutic agents.
Aripiprazole Offsets Mutant ATXN3-Induced Motor Dysfunction by Targeting Dopamine D2 and Serotonin 1A and 2A Receptors in C. elegans Ana Jalles, Cármen Vieira, Joana Pereira-Sousa, Daniela Vilasboas-Campos, Ana Francisca Mota, et al. Biomedicines, 2022 The 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 agonism and functional selectivity have been proposed as the main pharmacological mechanism of action of aripiprazole in the treatment of psychosis; however, this mechanism remains to be determined in the context of MJD. Here, we focus on confirming the efficacy of aripiprazole to reduce motor dysfunction in vivo, using a Caenorhabditis elegans (C. elegans) model of MJD, and on unveiling the drug targets required for its positive action against mutant ATXN3 pathogenesis. We employed pharmacogenetics and pharmacological approaches to identify which dopamine and serotonin receptors are critical for aripiprazole-mediated improvements in motor function. We demonstrated that dopamine D2-like and serotonin 5-HT1A and 5-HT2A receptors play important roles in this process. Our findings strengthen the relevance of dopaminergic and serotoninergic signaling modulation against mutant ATXN3-mediated pathogenesis. The identification of aripiprazole’s cellular targets, relevant for MJD and perhaps other neurodegenerative diseases, may pave the way for prospective drug discovery and development campaigns aiming to improve the features of this prototypical compound and reduce side effects not negligible in the case of aripiprazole.
Aripiprazole Offsets Mutant ATXN3-Induced Motor Dysfunction by Targeting Dopamine D 2 and Serotonin 1A and 2A Receptors in C. elegans A Jalles, C Vieira, J Pereira-Sousa, D Vilasboas-Campos, AF Mota, ... Biomedicines 10 (2), 370 , 2022 2022 Citations: 10
Identification of the 5-HT1A serotonin receptor as a novel therapeutic target in a C. elegans model of Machado-Joseph disease J Pereira-Sousa, B Ferreira-Lomba, A Bellver-Sanchis, ... Neurobiology of Disease 152, 105278 , 2021 2021 Citations: 17
MOST CITED SCHOLAR PUBLICATIONS
Identification of the 5-HT1A serotonin receptor as a novel therapeutic target in a C. elegans model of Machado-Joseph disease J Pereira-Sousa, B Ferreira-Lomba, A Bellver-Sanchis, ... Neurobiology of Disease 152, 105278 , 2021 2021 Citations: 17
Aripiprazole Offsets Mutant ATXN3-Induced Motor Dysfunction by Targeting Dopamine D 2 and Serotonin 1A and 2A Receptors in C. elegans A Jalles, C Vieira, J Pereira-Sousa, D Vilasboas-Campos, AF Mota, ... Biomedicines 10 (2), 370 , 2022 2022 Citations: 10