University of Oklahoma Background
There is currently no treatment available to stop or slow the progression of Alzheimer’s disease (AD). A vicious cycle between neuroinflammation and neurodegeneration is triggered and sustained by amyloid β (Aβ) soluble aggregates in the brain of patients with AD. The defense proteins CAP37, cathepsin G (CG) and neutrophil elastase (NE), expressed in neutrophils and certain brain cells have shown promise for interrupting these pathogenic pathways. CAP37, CG and NE bind Aβ, which inhibits aggregation into neurotoxic/proinflammatory species. They also binds and inhibits pro-inflammatory receptors RAGE and TLR4 and pro-inflammatory ligand S100A9. Therapeutic peptides derived from CAP37, CG, or NE could provide a multi-targeted strategy to inhibit both neuroinflammation and neurodegeneration to synergistically inhibit AD progression.
Bioactive peptides derived from CG and CAP37 have been identified. They mimic the effects of full-length proteins and thus could be used for inhibition of the neurotoxic and proinflammatory effects of Aβ in AD and related diseases.
A peptide inhibits Aβ aggregation (A), Aß neurotoxicity (B) and targets receptors of Aβ aggregates (RAGE (C) and TLR4 (D)), as well as S100A9, another AD-associated pro-inflammatory mediator.
Stage of Development
Technology Readiness Level (TRL): 2
Further investigation underway to support the use of these peptides as a viable therapeutic strategy for AD.
In vitro: Investigate anti-inflammatory effects on human microglia
In vivo: Investigate the ability of these peptides to penetrate the brain
Potential ability to cross the bloodbrain barrier by RAGE-mediated transcytosis
Inhibition of amyloid-β aggregation, neuroinflammation and neurodegeneration for the treatment of:
Seeking industry partner for further development