(9/9) Our results show a new cell-autonomous mechanism to activate the IFN-I response in microglia. Interestingly, some PHD inhibitors are already in clinical use, and it would be interesting to see if they can improve microglial responses to Aß plaques.

29.05.2025 12:49 — 👍 0    🔁 0    💬 0    📌 0

(8/9) Mechanistically, FOXO3 –a transcriptional repressor of the IFN response– stability is regulated by PHD3. Interestingly, FOXO3 has been identified in human studies as a key factor in microglial responses doi.org/10.1016/j.ce..., and we now show that FOXO3 is associated with the IFN response.

29.05.2025 12:48 — 👍 1    🔁 0    💬 1    📌 0

(7/9) PHD3 deficiency correlates with a decrease in the AD microglia type-I IFN responses, decreased local Aß plaque pathology, and a rescue of the behavioral defects in AD mouse models.

29.05.2025 12:45 — 👍 1    🔁 0    💬 1    📌 0

(6/9) We now describe a new pathway that activates type-I IFN response in microglia controlled by HIF1 and PHD3, a transcriptional target of HIF1.

29.05.2025 12:45 — 👍 0    🔁 0    💬 1    📌 0

Non-productive angiogenesis disassembles Aß plaque-associated blood vessels - Nature Communications Aß are extracellular deposits relevant in Alzheimer’s disease (AD). This study shows that Aß plaques are hubs of endothelial disassembly that induce non-productive angiogenesis. This process is aided ...

(5/9) Low oxygenation of the Aß plaques can be associated with local problems in angiogenesis www.nature.com/articles/s41...

29.05.2025 12:44 — 👍 1    🔁 0    💬 1    📌 0

Hypoxia compromises the mitochondrial metabolism of Alzheimer’s disease microglia via HIF1 - Nature Aging Microglia can help clear amyloid β plaques in the Alzheimer’s disease brain but may also become dysfunctional and can contribute to disease progression. March-Diaz et al. reveal that hypoxia, a potent...

(4/9) We have previously shown that Aß plaque-associated microglia have a strong HIF1-mediated response www.nature.com/articles/s43... @natmetabolism.nature.com

29.05.2025 12:43 — 👍 1    🔁 0    💬 1    📌 0

(3/9) It has been nicely demonstrated that microglial type-I IFN response is required for normal physiology and can be detrimental to the brain in chronic neurodegenerative diseases. The main controller of this response is the cGAS-STING pathway (see, for instance, www.cell.com/trends/neuro...

29.05.2025 12:42 — 👍 1    🔁 0    💬 1    📌 0

(2/9) We have characterized an unexpected cell-autonomous system to induce type-I interferon response in AD microglia.

29.05.2025 12:41 — 👍 1    🔁 0    💬 1    📌 0

Inactivation of the PHD3-FOXO3 axis blunts the type I interferon response in microglia and ameliorates Alzheimer’s disease progression PHD3 inhibition slows down the pathology and behavioral decline of an Alzheimer’s disease mouse model.

Really happy to see our work on Alzheimer’s disease (AD) microglia published in @science.org www.science.org/doi/10.1126/.... A great work at IBiS from Manuel Sanchez-Garcia, Nieves Lara-Ureña, Rosana March-Diaz, @alicielena.bsky.social , and all our collaborators.

29.05.2025 12:40 — 👍 3    🔁 2    💬 3    📌 1