Description
Aftin-4 is an inducer of amyloid-β (1-42) (Aβ42). It selectively increases extracellular Aβ42 over Aβ40 production in N2a-AβPP695 cells when used at concentrations ranging from 1 to 100 mM.
In vivo, aftin-4 (3-20 nmol/animal, i.c.v.) increases hippocampal Aβ42 content, lipid peroxidation, and production of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α in mice. It also induces spatial working and spatial reference memory deficits in mice, effects that are reversed by co-administration of the γ-secretase inhibitor BMS-299,897.
Uses
Aftin 4, is an Amyloid-β42 (Aβ42) inducer, that increases Aβ1-42 levels in vivo in mice and provokes rapidly a sustained toxicity highly reminiscent of Alzheimer’s disease (AD).
Biochem/physiol Actions
Aftin-4, an amyloid forty-two inducer, activates γ-secretase, promoting the generation of amyloid-β-1-42 (Aβ1-42) from amyloid-β protein precursor. Aftin-4 increased Aβ-1-42, but not Aβ-1-40 in mouse hipppocampus, accompanied by learning deficits and mitochondrial ultrastructural changes similar to those found in the brains of patients with AD. Aftin-4 can thus be used to induce a rapid, acute Alzheimer′s disease-like toxicity in the rodent brain.