Bruna Melissa Ferreira da Lomba

EDUCATION

BSc in Applied Biology
MSc in Health Sciences

RESEARCH, TEACHING, or OTHER INTERESTS

Neuroscience, Biochemistry, Genetics and Molecular Biology

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, Qiong Wang, Andreia Teixeira-Castro, Xinmin Liu, Fengzhong Wang, Alberto C. P. Dias, Patrícia Maciel
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, Sara Vasconcelos, Bruna Ferreira-Lomba, Marta Daniela Costa, Jorge Diogo Da Silva, Patrícia Maciel, Andreia Teixeira-Castro
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.
Identification of the 5-HT1A serotonin receptor as a novel therapeutic target in a C. elegans model of Machado-Joseph disease
Joana Pereira-Sousa, Bruna Ferreira-Lomba, Aina Bellver-Sanchis, Daniela Vilasboas-Campos, Jorge H. Fernandes, Marta D. Costa, Mark A. Varney, Adrian Newman-Tancredi, Patrícia Maciel, Andreia Teixeira-Castro
Neurobiology of Disease, 2021
Machado-Joseph disease (MJD) or Spinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disorder that affects movement coordination leading to a premature death. Despite several efforts, no disease-modifying treatment is yet available for this disease. Previous studies pinpointed the modulation of serotonergic signaling, through pharmacological inhibition of the serotonin transporter SERT, as a promising therapeutic approach for MJD/SCA3. Here, we describe the 5-HT1A receptor as a novel therapeutic target in MJD, using a C. elegans model of ATXN3 proteotoxicity. Chronic and acute administration of befiradol (also known as NLX-112), a highly specific 5-HT1A agonist, rescued motor function and suppressed mutant ATXN3 aggregation. This action required the 5-HT1A receptor orthologue in the nematode, SER-4. Tandospirone, a clinically tested 5-HT1A receptor partial agonist, showed a limited impact on animals' motor dysfunction on acute administration and a broader receptor activation profile upon chronic treatment, its effect depending on 5-HT1A but also on the 5-HT6/SER-5 and 5-HT7/SER-7 receptors. Our results support high potency and specificity of befiradol for activation of 5-HT1A/SER-4 receptors and highlight the contribution of the auto- and hetero-receptor function to the therapeutic outcome in this MJD model. Our study deepens the understanding of serotonergic signaling modulation in the suppression of ATXN3 proteotoxicity and suggests that a potent and selective 5-HT1A receptor agonist such as befiradol could constitute a promising therapeutic agent for MJD.

RECENT SCHOLAR PUBLICATIONS

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