Integrated Behavioral and Proteomic Characterization of MPP+-Induced Early Neurodegeneration and Parkinsonism in Zebrafish Larvae
Abstract
1. Introduction
2. Results
2.1. Evaluation of Locomotor Behavior Reveals Parkinsonian Motor Features in MPP+-Exposed Zebrafish Larvae
2.2. MPP+ Exposure Elicits Broad Proteomic Dysregulation in Zebrafish Larvae
2.3. Top Differentially Expressed Proteins Involved in Neurodegeneration-Related Processes
2.4. Coordinated Dysregulation of Parkinsonism-Associated Proteins
3. Discussion
4. Materials and Methods
4.1. Zebrafish Maintenance and Embryo Collection
4.2. Early Neurotoxic Exposure Protocol Using MPP+
4.3. Behavioral Analysis
4.4. Sample Preparation for Proteomic Analysis
4.5. Protein Quantification
4.6. Mass Spectrometry Analysis
4.7. Proteomic Data Analysis and Bioinformatics
4.8. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
PD | Parkinson’s disease |
MPP+ | 1-Methyl-4-phenylpyridinium |
DA | Dopaminergic |
CNS | Central nervous system |
DJ-1 | Parkinsonism-associated deglycase (also known as PARK7) |
SDHA | Succinate dehydrogenase complex flavoprotein subunit A |
PPI | Protein–protein interaction |
MS | Mass spectrometry |
LC–MS/MS | Liquid chromatography–tandem mass spectrometry |
GO | Gene Ontology |
FDR | False discovery rate |
log2FC | Log2 fold change |
KEGG | Kyoto Encyclopedia of Genes and Genomes |
ATP | Adenosine triphosphate |
ROS | Reactive oxygen species |
PBS | Phosphate-buffered saline |
dpf | Days post-fertilization |
hpf | Hours post-fertilization |
DEPs | Differentially expressed proteins |
TCA cycle | Tricarboxylic acid cycle |
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Gene Symbol | Protein Name | Log2FC | Reg |
---|---|---|---|
ACADVL | Very long-chain specific acyl-CoA dehydrogenase, mitochondrial | 1.562 | ↑ |
ACAT1 | Acetyl-CoA acetyltransferase, mitochondrial | 4.168 | ↑ |
ALCAMA | CD166 antigen homolog A | 2.412 | ↑ |
ATP2A2A | Calcium-transporting ATPase | −2.398 | ↓ |
ATP2B1A | Calcium-transporting ATPase | −2.477 | ↓ |
ATP2B4 | ATPase, Ca++ transporting, plasma membrane 4 | −1.882 | ↓ |
ATP5MJ | 6.8 kDa mitochondrial proteolipid-like | 2.322 | ↑ |
ATP5PD | ATP synthase subunit d, mitochondrial | 1.499 | ↑ |
CAMK2B1 | calcium/calmodulin-dependent protein kinase | −1.503 | ↓ |
CAPN2L | Calpain-2 catalytic subunit | −5.777 | ↓ |
CKMT2B | Creatine kinase S-type, mitochondrial | 1.477 | ↑ |
CS | Citrate synthase, mitochondrial | −1.614 | ↓ |
DLST | Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial | −1.652 | ↓ |
DMGDH | Dimethylglycine dehydrogenase, mitochondrial | −3.745 | ↓ |
DNAH2 | Dynein axonemal heavy chain 2 isoform X1 | 2.464 | ↑ |
FDX1 | Adrenodoxin, mitochondrial | 1.468 | ↑ |
ICN2 | Protein S100 | −1.669 | ↓ |
INAB | Internexin neuronal intermediate filament protein, alpha b | −1.694 | ↓ |
LONP1 | Lon protease homolog, mitochondrial | 1.827 | ↑ |
NDUFS6 | NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial | 1.77 | ↑ |
NEFMB | Neurofilament medium chain b | −2.489 | ↓ |
PARK7 | Parkinson disease protein 7 homolog | 1.946 | ↑ |
PRDX3 | Thioredoxin-dependent peroxide reductase, mitochondrial | −1.548 | ↓ |
PSMA8 | Proteasome subunit alpha type | 2.005 | ↑ |
PSMB10 | Proteasome subunit beta | 3.793 | ↑ |
PSMB3 | Proteasome subunit beta | 2.26 | ↑ |
PSMB5 | Proteasome subunit beta | 3.372 | ↑ |
PSMC1B | Proteasome | 2.198 | ↑ |
PSMC5 | 26S proteasome regulatory subunit 8 | −3.234 | ↓ |
PSMD11B | 26S proteasome non-ATPase regulatory subunit 11B | 1.633 | ↑ |
SDHA | Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial | −2.272 | ↓ |
SI:CH211-125O16.4 | Neuroblast differentiation-associated protein AHNAK | −1.567 | ↓ |
SLC25A11 | Mitochondrial 2-oxoglutarate/malate carrier protein | −2.773 | ↓ |
SLC25A3B | Solute carrier family 25 member 3 | −2.134 | ↓ |
STIP1 | Stress-induced-phosphoprotein 1 | −1.573 | ↓ |
TOMM7 | Mitochondrial import receptor subunit TOM7 homolog | 1.909 | ↑ |
UQCRC1 | Cytochrome b-c1 complex subunit 1, mitochondrial | 2.115 | ↑ |
UQCRFS1 | Cytochrome b-c1 complex subunit Rieske, mitochondrial | −1.516 | ↓ |
VAMP2 | Vesicle-associated membrane protein 2 | −4.728 | ↓ |
VAPB | Vesicle-associated membrane protein-associated protein B/C isoform X1 | 3.207 | ↑ |
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Maleski, A.L.A.; da Cunha e Silva, F.A.; Echeverry, M.B.; Alberto-Silva, C. Integrated Behavioral and Proteomic Characterization of MPP+-Induced Early Neurodegeneration and Parkinsonism in Zebrafish Larvae. Int. J. Mol. Sci. 2025, 26, 6762. https://doi.org/10.3390/ijms26146762
Maleski ALA, da Cunha e Silva FA, Echeverry MB, Alberto-Silva C. Integrated Behavioral and Proteomic Characterization of MPP+-Induced Early Neurodegeneration and Parkinsonism in Zebrafish Larvae. International Journal of Molecular Sciences. 2025; 26(14):6762. https://doi.org/10.3390/ijms26146762
Chicago/Turabian StyleMaleski, Adolfo Luis Almeida, Felipe Assumpção da Cunha e Silva, Marcela Bermudez Echeverry, and Carlos Alberto-Silva. 2025. "Integrated Behavioral and Proteomic Characterization of MPP+-Induced Early Neurodegeneration and Parkinsonism in Zebrafish Larvae" International Journal of Molecular Sciences 26, no. 14: 6762. https://doi.org/10.3390/ijms26146762
APA StyleMaleski, A. L. A., da Cunha e Silva, F. A., Echeverry, M. B., & Alberto-Silva, C. (2025). Integrated Behavioral and Proteomic Characterization of MPP+-Induced Early Neurodegeneration and Parkinsonism in Zebrafish Larvae. International Journal of Molecular Sciences, 26(14), 6762. https://doi.org/10.3390/ijms26146762