Technologies
This technology is a targeted approach to modulate neuroproteasome activity, enabling precise regulation of Tau aggregation in Alzheimer’s disease and related neurodegenerative disorders.
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.
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.
Patent Issued (WO/2024/118561)
IR CU23159, CU24106
Licensing Contact: Jerry Kokoshka