Lachén-Montes, M.; Cartas-Cejudo, P.; Cortés, A.; Anaya-Cubero, E.; Peral, E.; Ausín, K.; Díaz-Peña, R.; Fernández-Irigoyen, J.; Santamaría, E. Involvement of Glucosamine 6 Phosphate Isomerase 2 (GNPDA2) Overproduction in β-Amyloid- and Tau P301L-Driven Pathomechanisms. Biomolecules2024, 14, 394.
Lachén-Montes, M.; Cartas-Cejudo, P.; Cortés, A.; Anaya-Cubero, E.; Peral, E.; Ausín, K.; Díaz-Peña, R.; Fernández-Irigoyen, J.; Santamaría, E. Involvement of Glucosamine 6 Phosphate Isomerase 2 (GNPDA2) Overproduction in β-Amyloid- and Tau P301L-Driven Pathomechanisms. Biomolecules 2024, 14, 394.
Lachén-Montes, M.; Cartas-Cejudo, P.; Cortés, A.; Anaya-Cubero, E.; Peral, E.; Ausín, K.; Díaz-Peña, R.; Fernández-Irigoyen, J.; Santamaría, E. Involvement of Glucosamine 6 Phosphate Isomerase 2 (GNPDA2) Overproduction in β-Amyloid- and Tau P301L-Driven Pathomechanisms. Biomolecules2024, 14, 394.
Lachén-Montes, M.; Cartas-Cejudo, P.; Cortés, A.; Anaya-Cubero, E.; Peral, E.; Ausín, K.; Díaz-Peña, R.; Fernández-Irigoyen, J.; Santamaría, E. Involvement of Glucosamine 6 Phosphate Isomerase 2 (GNPDA2) Overproduction in β-Amyloid- and Tau P301L-Driven Pathomechanisms. Biomolecules 2024, 14, 394.
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 from 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 signalling or cellular stress responses. In contrast, the presence of beta-amyloid or mutated Tau-P301L in GNPDA2-overexpressing NECs induced a slow-down 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 nor 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=187). These data shed new light on GNPDA2-dependent mechanisms associated to the neurodegenerative process beyond the hexosamine route.
Keywords
GNPDA2; neurodegeneration; olfaction; zebrafish
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
,
,
,
,
,
*
