Dual-specificity protein phosphatase 4 (DUSP4) as a therapeutic target for alzheimer's disease neuroinflammation
Research platform exploring DUSP4 gene therapy to reduce neuroinflammation and amyloid plaque load in Alzheimer's disease. Preclinical evidence shows hippocampal DUSP4 overexpression mitigates neuroglial inflammatory responses, positioning DUSP4 as a promising target for neurodegenerative drug discovery.
Overview
This research program investigates dual-specificity protein phosphatase 4 (DUSP4) as a regulator of neuroinflammation in Alzheimer's disease (AD). Preclinical studies using an AD mouse model demonstrated that AAV5-mediated DUSP4 overexpression in the hippocampus reduced both neuroinflammation and amyloid plaque burden. Transcriptomic and proteomic analyses confirmed downregulation of inflammatory pathways following DUSP4 delivery. The work aims to elucidate the mechanistic role of DUSP4 in microglial activation and identify novel therapeutic targets for AD.
Technical specifications
Key features:
- AAV5-based gene delivery platform for targeted hippocampal DUSP4 overexpression
- Transcriptomic and proteomic profiling pipeline to identify differentially expressed genes and proteins (p < 0.05 cut-off)
- Enrichment analysis framework for mapping inflammatory pathway regulation
- Microglial-specific transgenic mouse model (Iba1 promoter-driven Dusp4 overexpression) crossed with APP/PS1 AD model
- Primary microglia isolation and stimulation assays using amyloid oligomers and lipopolysaccharide to model AD-associated inflammation
- Tyrobp transgenic construct platform previously validated for microglial-specific gene expression
Technology readiness level
This program is at an early preclinical stage (TRL 3–4). Initial validation has been completed in an AD mouse model with transcriptomic and proteomic confirmation of anti-inflammatory effects. Planned next steps include generating a novel microglial-specific Dusp4-overexpressing transgenic mouse line, crossing it with the APP/PS1 AD model, and conducting mechanistic studies in primary microglia. Further investigation is required to fully characterize the molecular mechanisms before translational development.
About Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai is a private academic medical center in New York City, anchored by a large, integrated health system. Co-located clinical and research facilities enable bedside-to-bench collaboration and rapid study startup across diverse patient populations. Industry partners benefit from system-wide EHR-linked biobanking, centralized contracting, and translational cores that support validation and clinical adoption. Research is primarily supported by the National Institutes of Health, with additional competitive federal funding. A dedicated technology transfer office provides IP strategy, licensing, and startup support.
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