eNAMPT-IFITM3 axis links neuroinflammation to γ-secretase activation.

Junho Hyun, Sunmin Jung, Yoona Noh, Yeonsu Cho, Takaomi C Saido, Jihoon Nah, Ki Woo Kim, Yong-Keun Jung

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In one paragraph

Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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8 authors.

Junho HyunSchool of Biological Science, Seoul National University, Seoul 08826, Korea.

Sunmin JungAdvanced-Basic-Convergence Research Institute, Chungbuk National University, Cheongju 28644, Korea.

Yoona NohAdvanced-Basic-Convergence Research Institute, Chungbuk National University, Cheongju 28644, Korea.

Yeonsu ChoAdvanced-Basic-Convergence Research Institute, Chungbuk National University, Cheongju 28644, Korea.

Takaomi C SaidoLaboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako-Shi, Japan.

Jihoon NahAdvanced-Basic-Convergence Research Institute, Chungbuk National University, Cheongju 28644, Korea.

Ki Woo KimDivision of Physiology, Yonsei University College of Dentistry, Seoul 03722, Korea.

Yong-Keun JungSchool of Biological Science, Seoul National University, Seoul 08826, Korea.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Amyloid-β (Aβ) accumulation and neuroinflammation are central features of Alzheimer's disease (AD), yet the molecular link connecting inflammatory signaling to γ-secretase activation remains poorly understood. Here, using a cell-based gain-of-function screen with a cDNA library, we identify nicotinamide phosphoribosyltransferase (NAMPT) as a positive regulator of γ-secretase activity. We demonstrate that extracellular NAMPT (eNAMPT) acts as a paracrine factor binding to cell-surface interferon-induced transmembrane protein 3 (IFITM3), enhancing its protein stability and promoting γ-secretase complex assembly to heighten amyloidogenic processing, independently of its NAD+ biosynthetic function. Pathologically, NAMPT levels are elevated in patients with AD and mouse models. Furthermore, systemic inflammation induced by lipopolysaccharide (LPS) enhances NAMPT expression and promotes the NAMPT-IFITM3 interaction and γ-secretase complex assembly

Indexed as

Alzheimer’s diseaseamyloid betaIFITM3NAMPTγ-secretase

Identifiers

PMID42765029

DOI10.1016/j.isci.2026.117496

PMCPMC13590055

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.