Biology subjects

Cavalcante, G. C.

Publications and source records attributed to Cavalcante, G. C..

4 recordsLinked to original sources

bioRxiv2026

Mitochondrial Metabolism and Calcium Handling in Parkinsons Disease hiPSC-derived Astrocytes

Parkinsons disease (PD) is the second most common neurodegenerative disorder worldwide, and mutations in the LRRK2 and PRKN genes are among the most common familial causes of the disease. In neurodegenerative diseases such as PD, disturbances in Ca{superscript 2} homeostasis and cellular bioenergetics impair the function of neurons and glial cells, contributing to disease progression. These changes are not limited to neurons; mitochondrial dysfunction and disrupted Ca2+ homeostasis in astrocytes are increasingly recognized as key contributors to PD, impairing bioenergetics, redox balance, neuroinflammatory responses, and metabolic support essential for dopaminergic neuron survival. In this study, we investigated mitochondrial calcium homeostasis, mitochondrial oxidative phosphorylation, morphology and distribution in human induced pluripotent stem cell (hiPSC)-derived astrocytes with mutations in the PD genes LRRK2 (G2019S) and PRKN (c.155delA; Ex3-4del) and wild-type controls. Intracellular calcium dynamics were assessed using Fura-2 AM. Compared with control astrocytes, LRRK2-related PD patient-derived mutant astrocytes exhibited lower intracellular calcium levels, and slower calcium extrusion following stimulation with ATP. Mitochondrial morphology was analyzed using MitoTracker Deep Red, revealing increased mitochondrial fragmentation and redistribution of mitochondria toward the cell periphery in both PD mutant cell types. Because oxidative phosphorylation is tightly regulated by mitochondrial morphology and calcium homeostasis, we next assessed oxygen consumption rates using a continuous metabolic monitoring system (Resipher) and quantified the expression of genes (RT-qPCR) and proteins (capillary electrophoresis-based western detection) involved in mitochondrial calcium transport and bioenergetics. These analyses showed that PRKN mutant astrocytes exhibit a more oxidative bioenergetic phenotype than LRRK2 mutant astrocytes, while both mutant lines displayed altered phosphorylation of mitochondrial morphology regulator DRP1 as well as decreased levels of respiratory complexes relative to control astrocytes. In summary, this study identifies astrocyte-specific mitochondrial dysfunctions and calcium dysregulation as key features of LRRK2- and PRKN-related pathology, providing new insights into how glial metabolic alterations contribute to neurodegeneration in PD.

neuroscience↗

bioRxiv2026

mtDNA-Network: a web tool to explore mitochondrial variant profiles in complex diseases

The mitochondrial genome (mtDNA) provides valuable insights into human evolution, population diversity, and disease etiology. Here, we present the mtDNA-network (https://apps.lghm.ufpa.br/mtdna/), an integrative bioinformatics database and tool for the visualization and analysis of mitochondrial variants (single-nucleotide variants and insertions/deletions). The mtDNA-network was upgraded to enable investigation of mtDNA in admixed Brazilian individuals with substantial contributions from uniparental Indigenous and African ancestries. We implement a bioinformatics pipeline to harmonize variant calling across 339 mtDNA samples. The dataset supports general genetic population analysis and variant mapping for complex diseases, including Parkinsons disease (104 cases and 75 controls), leprosy (33 cases and 37 controls), and somatic gastric cancer (40 cases and 50 controls). The mtDNA-network tool features an intuitive interface and analytical dashboards for transitions, transversions, heteroplasmy, and variant-disease networks, and serves as a strategic resource for advancing research in population genetics and precision medicine in underrepresented populations. We reinforce the critical need to expand non-European genomic representation in global databases to promote more equitable genomic diversity studies and clinically relevant discoveries.

bioinformatics↗

bioRxiv2026

An Open-Source Code To Analyze Mitochondrial Intracellular Distribution From Fluorescence Microscopy Images

Mitochondria have a plethora of roles in cells, many of which are related to dynamic changes in their size, shape, and intracellular location. Mitochondrial morphology is commonly assessed by microscopy with targeted fluorescent probes. However, tools to easily estimate mitochondrial localization within a cell are still lacking. A code was designed to estimate per-cell mitochondrial radial localization (perinuclear or peripheral) from fluorescence microscopy files in a variety of formats and using different mitochondrial markers (https://github.com/cavalcantegc/mito_localization.git). Three case studies with different cell types and stainings demonstrate that mitochondrial localization can be easily extracted and plotted with this code.

cell biology↗

bioRxiv2025

Downregulation of the Ca2+ sensor Synaptotagmin-1 (SYT1) in Parkinson's Disease: Insights from Gene Expression Profiling

Parkinsons disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons and by the intracellular accumulation of alpha-synuclein, leading to motor and non-motor symptoms. Despite being a widely studied disease, so new mechanisms should be investigated as possible paths for future diagnostics and treatments in PD. Here, we performed an in silico analysis of the global gene expression of tissues from different brain regions (prefrontal area, putamen, and substantia nigra) in PD patients and controls, to demonstrate differentially expressed genes (DEGs). We analyzed the dataset series GSE20295 from GEO, which comprises GSE20168, GSE20291, and GSE20292. We identified 13 DEGs, all exhibiting downregulation in PD tissues compared to controls. Notably, the SYT1 (Synaptotagmin-1) gene demonstrated the lowest expression level and nearly the most significant adjusted p-value. SYT1 is implicated in calcium ion sensor activity, a functional domain showing substantial fold enrichment in our study. This gene encodes a protein pivotal for neurotransmitter release at synapses. We also found a significant role of calcium-related processes in PD pathology through GSEA, indicating an overall increase in their activity and a disruption in neurotransmitter release mechanisms mediated by Ca2+. Despite limited research on the correlation between SYT1 and PD to date, our findings suggest the SYT1 gene holds promise as a possible target for PD. Further investigations are needed to elucidate this association fully.

bioinformatics↗