PUBLICATION
Involvement of Glucosamine 6 Phosphate Isomerase 2 (GNPDA2) Overproduction in β-Amyloid- and Tau P301L-Driven Pathomechanisms
- Authors
- Lachén-Montes, M., Cartas-Cejudo, P., Cortés, A., Anaya-Cubero, E., Peral, E., Ausín, K., Díaz-Peña, R., Fernández-Irigoyen, J., Santamaría, E.
- ID
- ZDB-PUB-240428-19
- Date
- 2024
- Source
- Biomolecules 14(4): (Journal)
- Registered Authors
- Keywords
- GNPDA2, neurodegeneration, olfaction, zebrafish
- MeSH Terms
-
- Humans
- Cell Proliferation
- Amyloid beta-Peptides*/metabolism
- tau Proteins*/genetics
- tau Proteins*/metabolism
- Proteomics
- Epithelial Cells/metabolism
- Animals, Genetically Modified
- Animals
- Zebrafish*/metabolism
- Aldose-Ketose Isomerases/genetics
- Aldose-Ketose Isomerases/metabolism
- Alzheimer Disease*/genetics
- Alzheimer Disease*/metabolism
- Alzheimer Disease*/pathology
- PubMed
- 38672412 Full text @ Biomolecules
Citation
Lachén-Montes, M., Cartas-Cejudo, P., Cortés, A., Anaya-Cubero, E., Peral, E., Ausín, K., Díaz-Peña, R., Fernández-Irigoyen, J., Santamaría, E. (2024) Involvement of Glucosamine 6 Phosphate Isomerase 2 (GNPDA2) Overproduction in β-Amyloid- and Tau P301L-Driven Pathomechanisms. Biomolecules. 14(4):.
Abstract
Alzheimer's disease (AD) is a neurodegenerative olfactory disorder affecting millions of people worldwide. Alterations in the hexosamine- or glucose-related pathways have been described through AD progression. Specifically, an alteration in glucosamine 6 phosphate isomerase 2 (GNPDA2) protein levels has been observed in olfactory areas of AD subjects. However, the biological role of GNPDA2 in neurodegeneration remains unknown. Using mass spectrometry, multiple GNPDA2 interactors were identified in human nasal epithelial cells (NECs) mainly involved in intraciliary transport. Moreover, GNPDA2 overexpression induced an increment in NEC proliferation rates, accompanied by transcriptomic alterations in Type II interferon signaling or cellular stress responses. In contrast, the presence of beta-amyloid or mutated Tau-P301L in GNPDA2-overexpressing NECs induced a slowdown in the proliferative capacity in parallel with a disruption in protein processing. The proteomic characterization of Tau-P301L transgenic zebrafish embryos demonstrated that GNPDA2 overexpression interfered with collagen biosynthesis and RNA/protein processing, without inducing additional changes in axonal outgrowth defects or neuronal cell death. In humans, a significant increase in serum GNPDA2 levels was observed across multiple neurological proteinopathies (AD, Lewy body dementia, progressive supranuclear palsy, mixed dementia and amyotrophic lateral sclerosis) (n = 215). These data shed new light on GNPDA2-dependent mechanisms associated with the neurodegenerative process beyond the hexosamine route.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping