Neuroproteasome-inhibiting bioconjugate for prevention of tau aggregation in Alzheimer's disease
This technology is a targeted approach to modulate neuroproteasome activity, enabling precise regulation of Tau aggregation in Alzheimer’s disease and related neurodegenerative disorders.
Unmet Need: Methods to prevent Tau aggregation to treat Alzheimer’s disease
Current Tau aggregate-targeting therapies for Alzheimer’s disease, including immunotherapies and small molecules, have shown limited success in stopping disease progression. While protein degradation pathways regulate protein balance and function, their role in Tau aggregation remains unclear. Conventional proteasome-targeting therapies lack the precision needed to enhance neuronal protein clearance without disrupting essential cellular functions. Although proteasomes are critical for protein degradation, no targeted strategies exist to directly modulate their activity to prevent endogenous Tau aggregation in Alzheimer’s disease.
The Technology: Bioconjugate for modulation of neuroproteasomes to prevent Tau aggregation in Alzheimer’s disease
This technology is a bioconjugate which selectively inhibits neuroproteasomes, a specialized subset of proteasomes at neuronal membranes, to regulate Tau protein aggregation. The technology is comprised of a cell-impermeable moiety attached via a PEG linker a proteosome inhibitor. By modulating neuroproteasome activity, this technology influences the degradation of newly synthesized Tau, preventing its accumulation and misfolding. The approach takes advantage of the differential regulation of neuroproteasome localization by ApoE isoforms, providing a targeted method to intervene in Tau-associated neurodegeneration. This enables more precise control over mechanisms of protein regulation in neurons, addressing a critical gap in Alzheimer’s disease treatment strategies.
Applications:
- Treatment of Alzheimer’s disease (AD)
- Treatment of neurodegenerative diseases linked to Tau aggregation
- Targeted proteostasis therapies
- Biomarker discovery for Tauopathies
- Research tool for neuroproteasome function
- ApoE-targeted therapeutics
Advantages:
- Targets early-stage Tau aggregation for intervention
- Provides a novel approach to modulating neuroproteasomes
- Enhances specificity over conventional proteasome-targeting therapies
- Reduces off-target effects on cellular protein degradation
Lead Inventor:
Patent Information:
Patent Issued (WO/2024/118561)
Related Publications:
Tech Ventures Reference:
IR CU23159, CU24106
Licensing Contact: Jerry Kokoshka