RT Journal Article
T1 Hypoxia compromises the mitochondrial metabolism of Alzheimer’s disease microglia via HIF1
A1 March-Diaz, Rosana
A1 Lara-Ureña, Nieves
A1 Romero-Molina, Carmen
A1 Heras-Garvin, Antonio
A1 Ortega-de San Luis, Clara
A1 Alvarez-Vergara, Maria I
A1 Sanchez-Garcia, Manuel A
A1 Sánchez-Mejías, Elisabeth
A1 Dávila-Cansino, José Carlos
A1 Rosales-Nieves, Alicia E
A1 Forja, Cristina
A1 Navarro, Victoria
A1 Gomez-Arboledas, Ángela
A1 Sánchez-Mico, María Virtudes
A1 Viehweger, Adrian
A1 Gerpe, Almudena
A1 Hodson, Emma J
A1 Vizuete, Marisa
A1 Bishop, Tammie
A1 Serrano-Pozo, Alberto
A1 Lopez-Barneo, Jose
A1 Berra, Edurne
A1 Gutiérrez-Pérez, Antonia
A1 Vitorica Ferrández, Javier
A1 Pascual, Alberto
K1 Patología mitocondrial
K1 Oxígeno-Efectos fisiológicos
K1 Alzheimer, Enfermedad de
AB Genetic Alzheimer’s disease (AD) risk factors associate with reduced defensive amyloid β plaque-associated microglia (AβAM), but the contribution of modifiable AD risk factors to microglial dysfunction is unknown. In AD mouse models, we observe con- comitant activation of the hypoxia-inducible factor 1 (HIF1) pathway and transcription of mitochondrial-related genes in AβAM, and elongation of mitochondria, a cellular response to maintain aerobic respiration under low nutrient and oxygen conditions. Overactivation of HIF1 induces microglial quiescence in cellulo, with lower mitochondrial respiration and proliferation. In vivo, overstabilization of HIF1, either genetically or by exposure to systemic hypoxia, reduces AβAM clustering and proliferation and increases Aβ neuropathology. In the human AD hippocampus, upregulation of HIF1α and HIF1 target genes correlates with reduced Aβ plaque microglial coverage and an increase of Aβ plaque-associated neuropathology. Thus, hypoxia (a modifiable AD risk factor) hijacks microglial mitochondrial metabolism and converges with genetic susceptibility to cause AD microglial dysfunction.
PB Nature Research
YR 2021
FD 2021-04
LK https://hdl.handle.net/10630/34330
UL https://hdl.handle.net/10630/34330
LA eng
NO March-Diaz, R., Lara-Ureña, N., Romero-Molina, C. et al. Hypoxia compromises the mitochondrial metabolism of Alzheimer’s disease microglia via HIF1. Nat Aging 1, 385–399 (2021). https://doi.org/10.1038/s43587-021-00054-2
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026