Leandro Mantovani de Castro

@unesp.br

Bioscience Institute
Sao Paulo State University

EDUCATION

Graduated in Biomedicine from the University of Mogi das Cruzes (2000) and PhD in Biological Sciences (Molecular Biology) at Federal University of São Paulo

RESEARCH INTERESTS

Cell biology and mass spectrometry for the characterization, function and metabolism of proteins and bioactive peptides in different biological models
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Scopus Publications

Scopus Publications

  • Histopathological Alterations and Dysregulation of Type I Interferon Signaling in the Human Cerebral Cortex During Severe Dengue
    Leandro Mantovani de Castro, Elaine Raniero Fernandes, Juarez Antonio Simoes Quaresma, Carmen Lucia Penteado Lancelotti, Maria Irma Seixas Duarte, et al.
    Journal of Medical Virology, 2025
    Dengue virus (DENV) is a major arthropod‐borne pathogen, endemic in over 100 countries and posing global health challenges. While innate immune responses and viral evasion mechanisms have been extensively studied in animal models and mononuclear cells, severe dengue can affect multiple tissues, including the central nervous system (CNS), leading to neurological manifestations. However, the CNS immune response remains poorly understood. This study analyzed molecules linked to innate immunity in CNS lesions from fatal dengue cases. Histopathological examination of the cerebral cortex revealed marked neuronal damage—chromatolysis, pyknotic nuclei—accompanied by microglial hyperplasia, white matter demyelination, perivascular inflammation, vascular congestion, vasogenic edema, and occasional hemorrhage or meningitis. DENV antigen was detected in endothelial cells of cortical and leptomeningeal vessels and in glial cells or macrophages. Immunohistochemistry revealed altered expression of innate immune markers: RIG‐I was sparsely expressed, STING was absent, and IFN‐α/β levels were reduced compared to controls. Notably, IRF2 expression was markedly elevated, with strong labeling in neurons, glial, and endothelial cells. These findings suggest an atypical pattern of immune activation in the CNS during severe dengue and highlight a potential role for IRF2 in modulating cerebral immune responses, offering new insights into the neuropathogenesis of dengue.
  • Biotechnological Potential of the Fusarium fujikuroi Complex From Amazonian Oenocarpus bacaba: Lipase Production and Characterization
    Lucely Nogueira dos Santos, Rafael Firmani Perna, Ana Carolina Vieira, Kalebe Ferreira Furtado, Alex Fernando de Almeida, et al.
    Journal of Basic Microbiology, 2025
    This study investigates the diversity of filamentous fungi in the Amazon biome, particularly the genus Fusarium, known for producing biotechnologically valuable metabolites. The research aimed to isolate and identify fungi from Oenocarpus bacaba Mart. fruits and analyze the biochemical properties of lipase produced by the strains (maximum activity of 1750 U mL⁻¹). Two isolates, FF1 and FF2, were identified using morphological and molecular techniques, with ITS sequence data suggesting they belong to the Fusarium fujikuroi species complex, though the exact species remains unconfirmed. This is the first report that highlights the biotechnological potential of the F. fujikuroi complex isolated from Oenocarpus bacaba, emphasizing the relevance of Amazonian biodiversity as a source of microorganisms with promising applications in sustainable industrial processes. The results show that native fruits, such as bacaba, are effective matrices for prospecting filamentous fungi producers of enzymes of biotechnological interest, such as lipases. These findings reinforce the importance of rational exploitation of the Amazonian microbiota for the development of bioproducts and eco‐efficient industrial processes.
  • Molecular Insights into the Marine Gastropod Olivancillaria urceus: Transcriptomic and Proteopeptidomic Approaches Reveal Polypeptides with Putative Therapeutic Potential
    Gabriel Marques de Barros, Letícia Fontes Gama, Felipe Ricardo de Mello, Claudia Neves Corrêa, Louise Oliveira Fiametti, et al.
    International Journal of Molecular Sciences, 2025
    The marine environment is a rich source of new biotechnologies and products. Bottom trawling for shrimp species such as Xiphopenaeus kroyeri and Farfantepenaeus brasiliensis leads to the unintentional capture of non-target species, known as bycatch, which includes a variety of marine life that are often discarded without economic value. A common bycatch species on the southeast coast of Brazil is Olivancillaria urceus (O. urceus), a carnivorous gastropod that feeds mainly on bivalves. Despite its abundance, this species is still little studied, especially for biotechnological applications. Other gastropods such as Conus are known for their diverse and potent toxins, which offer great potential for pharmacological discoveries. In this study, an omics approach, including transcriptomics and proteopeptidomics, was applied to explore O. urceus at the molecular level. The transcriptome of the muscle foot/mantle led to the annotation of 19,097 genes via Gene Ontology, identifying 20 toxin-like transcripts identified considering the Gastropod class. The proteome fraction confirmed 2179 transcripts, including sequences with toxin activity, such as conotoxin precursors, Conodipine-P3, and BPTI/Kunitz domain-containing proteins. In addition, 9663 peptides of 1484 precursor proteins were detected in the peptide fraction, including 2 sequences representing neurotoxins. The identification of these sequences could lead to the discovery of new molecules with therapeutic potential.
  • Study of Intracellular Peptides of the Central Nervous System of Zebrafish (Danio rerio) in a Parkinson’s Disease Model
    Louise O. Fiametti, Camilla A. Franco, Leticia O. C. Nunes, Leandro M. de Castro, Norival A. Santos-Filho
    International Journal of Molecular Sciences, 2025
    Although peptides have been shown to have biological functions in neurodegenerative diseases, their role in Parkinson’s disease has been understudied. A previous study by our group, which used a 6-hydroxydopamine zebrafish model, suggested that nine intracellular peptides may play a part in this condition. In this context, our aim is to better understand the role of five of these nine peptides. The selection of peptides was made based on their precursor proteins, which are fatty acid binding protein 7, mitochondrial ribosomal protein S36, MARCKS-related protein 1-B, excitatory amino acid transporter 2 and thymosin beta-4. The peptides were chemically synthesized in solid phase and characterized by high-performance liquid chromatography and mass spectrometry. Circular dichroism was performed to determine the secondary structure of each peptide, which showed that all five peptides maintain a random structure in the aqueous solutions that were studied. Two molecules show a helical profile in trifluoroethanol, a known structuring agent. Cell viability by the MTT assay indicates that all five peptides are not cytotoxic in all concentrations tested in both mouse and human cell lines. Behavioral assay using a 6-OHDA zebrafish larvae model suggest that all peptides help in the recovery of motor function with 24 h treatment at two concentrations. Three peptides showed a complete recovery from the 6-OHDA-induced motor impairment. Further studies are needed to better understand the mechanism of action of these peptides and whether they are truly a potential ally against Parkinson’s disease.
  • Marine Mycosilver Nanoparticles: Screening, Evaluation of Their Antimicrobial Properties, and Synthesis Optimization
    Caterina Trotta, Ana Laura Alves, Mariana Cardoso, Carolina da Silva, Patrícia Léo, et al.
    Sustainable Chemistry, 2025
    Twelve marine-derived fungal strains were evaluated for their ability to synthesize silver nanoparticles (AgNPs). Mycogenic AgNPs were preliminarily characterized using different techniques, and their antimicrobial activities were assessed. Penicillium citrinum IBCLP11 and Aspergillus niger IBCLP20 were selected for AgNPs’ synthesis optimization by varying parameters such as AgNO3 concentration, biomass, agitation, temperature, and pH. AgNPIBCLP11 and AgNPIBCLP20 were able to inhibit the growth of Pseudomonas aeruginosa IPT322, Staphylococcus aureus IPT246, and Klebsiella pneumoniae IPT412 at concentrations of 25 μg/mL or higher. Aspergillus niger IPT295 and Aspergillus parasiticus IPT729 were the most sensitive to AgNPIBCLP20. Further studies are needed to fully elucidate the effects of all parameters influencing mycogenic AgNPs synthesis. However, it is evident that maintaining optimal conditions, such as temperature and pH during agitation, is crucial for preventing undesirable reactions and ensuring nanoparticle stability.
  • Bioprospecting of Mangrove Filamentous Fungi for the Biodegradation of Polyethylene Microplastics
    Arthur Aguiar, Letícia Gama, Milene Fornari, Almir Neto, Rodrigo de Souza, et al.
    Journal of Marine Science and Engineering, 2024
    The accumulation of microplastics (MPs) in the environment has been a bottleneck for scientific society. Several approaches have been described as possibilities for reducing MPs in aquatic and terrestrial ecosystems; however, most of them are not environmentally friendly. Filamentous fungi (Ff) cells are currently considered a promising solution as a treatment for MPs. Therefore, the present study reports the potential ability of Ff isolated from mangrove sediments to biodegrade low-density polyethylene MPs (LDPEMPs). Six Ff strains were grown in batch cultures for 28 days, and one of them, Aspergillus sp. (AQ3A), showed the most prominent profile to biodegrade polymeric compounds. After morphological and molecular analysis, all strains were identified as belonging to the genera Aspergillus (MQ1C, AQ2A and AQ3A), Penicillium (MQ1A), and Trichoderma (MQ1B and MQ2A). The strain Aspergillus sp. (AQ3A) showed the most promising results with a LDPEMPs reduction rate of 47% and biomass formation of 0.0890 g·mL−1. Complementary studies with Aspergillus sp. (AQ3A) using Fourier-transform infrared spectroscopy (FTIR) highlighted changes in the molecular structure of LDPEMPs. These results indicate that Ff can contribute to the biodegradation of LDPEMPs. However, other parameters, mainly associated with the enzymes that are involved in this biodegradation process, need to be explored.
  • Peptidomics of Zebrafish Brain in a 6-OHDA-Induced Neurodegeneration Model
    Louise O. Fiametti, Felipe Ricardo de Mello, Leandro M. de Castro
    Methods in Molecular Biology, 2024
  • Quantitative Peptidomics Using Reductive Methylation of Amines
    Alexandre K. Tashima, Leandro M. de Castro, Lloyd D. Fricker
    Methods in Molecular Biology, 2024
  • Methods for Intracellular Peptidomic Analysis
    Rosangela A. S. Eichler, Luiz Felipe Martucci, Leandro M. de Castro, Emer S. Ferro
    Methods in Molecular Biology, 2024
  • Revealing Natural Intracellular Peptides in Gills of Seahorse Hippocampus reidi
    Claudia Neves Correa, Louise Oliveira Fiametti, Gabriel Marques de Barros, Leandro Mantovani de Castro
    Biomolecules, 2023
    The seahorse is a marine teleost fish member of the Syngnathidae family that displays a complex variety of morphological and reproductive behavior innovations and has been recognized for its medicinal importance. In the Brazilian ichthyofauna, the seahorse Hippocampus reidi is among the three fish species most used by the population in traditional medicine. In this study, a protocol was performed based on fast heat inactivation of proteases plus liquid chromatography coupled to mass spectrometry to identify native peptides in gills of seahorse H. reidi. The MS/MS spectra obtained from gills allowed the identification of 1080 peptides, of which 1013 peptides were present in all samples and 67 peptide sequences were identified in an additional LC-MS/MS run from an alkylated and reduced pool of samples. The majority of peptides were fragments of the internal region of the amino acid sequence of the precursor proteins (67%), and N- and C-terminal represented 18% and 15%, respectively. Many peptide sequences presented ribosomal proteins, histones and hemoglobin as precursor proteins. In addition, peptide fragments from moronecidin-like protein, described with antimicrobial activity, were found in all gill samples of H. reidi. The identified sequences may reveal new bioactive peptides.
  • Multiomic Approach for Bioprospection: Investigation of Toxins and Peptides of Brazilian Sea Anemone Bunodosoma caissarum
    Maria Eduarda Mazzi Esquinca, Claudia Neves Correa, Gabriel Marques de Barros, Horácio Montenegro, Leandro Mantovani de Castro
    Marine Drugs, 2023
  • Hidden by the name: A new fluorescent pumpkin toadlet from the Brachycephalus ephippium group (Anura: Brachycephalidae)
    Ivan Nunes, Carla S. Guimarães, Pedro Henrique A. G. Moura, Mariana Pedrozo, Matheus de Toledo Moroti, et al.
    Plos One, 2021
  • Peptide Profile of Zebrafish Brain in a 6-OHDA-Induced Parkinson Model
    Louise Oliveira Fiametti, Claudia Neves Correa, Leandro Mantovani de Castro
    Zebrafish, 2021
  • Sample preparation and relative quantitation using reductive methylation of amines for peptidomics studies
    Claudia Neves Correa, Louise Oliveira Fiametti, Maria Eduarda Mazzi Esquinca, Leandro Mantovani de Castro
    Journal of Visualized Experiments, 2021
  • Shell structure and composition alterations in the limpet Lottia subrugosa along a contamination gradient in the Santos Estuary, Brazil
    Carolina Rocha Moreira Oliveira, Leandro Mantovani de Castro, Monick Alves da Cruz Nazareth, Cyntia Ayumi Yokota Harayashiki, Ítalo Braga Castro
    Ecological Indicators, 2020
  • NFKF is a synthetic fragment derived from rat hemopressin that protects mice from neurodegeneration
    Andrea S. Heimann, A.C. Giardini, M.B. Sant’Anna, Nilton B. Dos Santos, Mayara C.F. Gewehr, et al.
    Neuroscience Letters, 2020
  • The relevance of thimet oligopeptidase in the regulation of energy metabolism and diet-induced obesity
    Mayara C. F. Gewehr, Alexandre A. S. Teixeira, Bruna A. C. Santos, Luana A. Biondo, Fábio C. Gozzo, et al.
    Biomolecules, 2020
  • Thimet oligopeptidase (EC 3.4.24.15) key functions suggested by knockout mice phenotype characterization
    Nilton dos Santos, Roseane Franco, Rosana Camarini, Carolina Munhoz, Rosangela Eichler, et al.
    Biomolecules, 2019
  • Characterization of Intracellular Peptides from Zebrafish (Danio rerio) Brain
    Caio Matheus Manzi Teixeira, Claudia Neves Correa, Leo Kei Iwai, Emer Suavinho Ferro, Leandro Mantovani de Castro
    Zebrafish, 2019
  • Effect of protein denaturation and enzyme inhibitors on proteasomal-mediated production of peptides in human embryonic kidney cells
    Sayani Dasgupta, Michael A. Fishman, Leandro M. Castro, Alexandre K. Tashima, Emer S. Ferro, et al.
    Biomolecules, 2019
  • Effects of ocean acidification and salinity variations on the physiology of osmoregulating and osmoconforming crustaceans
    Andressa Cristina Ramaglia, Leandro Mantovani de Castro, Alessandra Augusto
    Journal of Comparative Physiology B Biochemical Systemic and Environmental Physiology, 2018
  • Marine biotechnology in Brazil: Recent developments and its potential for innovation
    Fabiano Thompson, Ricardo Krüger, Cristiane C. Thompson, Roberto G. S. Berlinck, Ricardo Coutinho, et al.
    Frontiers in Marine Science, 2018
  • Quantitative peptidomics using reductive methylation of amines
    Sayani Dasgupta, Leandro M. Castro, Alexandre K. Tashima, Lloyd Fricker
    Methods in Molecular Biology, 2018
  • Interferon-gamma activity is potentiated by an intracellular peptide derived from the human 19S ATPase regulatory subunit 4 of the proteasome
    Elisabete R.C. Monte, Cristiano Rossato, Ricardo Pariona Llanos, Lilian C. Russo, Leandro M. de Castro, et al.
    Journal of Proteomics, 2017
  • Analysis of the yeast peptidome and comparison with the human peptidome
    Sayani Dasgupta, Ciyu Yang, Leandro M. Castro, Alexandre K. Tashima, Emer S. Ferro, et al.
    Plos One, 2016