Searching for an endogenous anti-alzheimer molecule: Identifying small molecules in the brain that slow alzheimer disease progression by inhibition of β-amyloid aggregation

Background: alzheimer disease is a neurodegenerative disorder that progresses with marked interindividual clinical variability. we postulate the existence of endogenous molecules within the human brain exerting an antiaggregant activity that will prevent/slow alzheimer disease progression. methods: we performed in silico studies to determine if the small endogenous molecules l-phosphoserine (l-ps) and 3-hydroxyanthranilic acid (3-haa) could bind to the target region of β-amyloid responsible for protein misfolding. in vitro assays measured the antiaggregation effect of these molecules at varying concentrations. results: in silico studies demonstrated that l-ps and 3-haa,both endogenous brain molecules,were capable of binding to the histidine13-histidine-glutamine-lysine16(hhqk) region of β-amyloid involved in misfolding: these interactions were energetically favoured. the in vitro assays showed that both l-ps and 3-haa were capable of inhibiting β-amyloid aggregation in a dose-dependent manner,with 3-haa being more potent than l-ps. limitations: studies were performed in silico and in vitro but not in vivo. conclusion: we successfully identified 2 endogenous brain molecules,l-ps and 3-haa,that were capable of binding to the region of β-amyloid that leads to protein misfolding and neurotoxicity. both l-ps and 3-haa were able to inhibit β-amyloid aggregation in varying concentrations; levels of these compounds in the brain may impact their effectiveness in slowing/preventing β-amyloid aggregation.