- Simulated gastrointestinal digestion of phycobiliproteins yielded peptides P1 (GCAPR), P2 (QAGDQL) and P3 (AGDASVL), plus phycocyanobilin, for in-silico evaluation.
- Phycocyanobilin demonstrated strong binding to BChE (-10.0 kcal/mol) and GSK-3β (-8.4 kcal/mol), indicating tau and late-stage cholinergic modulation.
- Peptide P2 showed notable affinity to AChE (-8.8 kcal/mol) and BACE1 (-7.6 kcal/mol), supporting multi-target potential for functional food and nutraceutical development.
J Recept Signal Transduct Res. 2026 Aug 24:1-10. doi: 10.1080/10799893.2026.2723004. Online ahead of print.
ABSTRACT
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β (Aβ) accumulation, Tau hyperphosphorylation, and cholinergic dysfunction, necessitating multi-target therapeutic strategies. This study evaluated phycobiliproteins (PBPs) as dietary precursors of neuroprotective compounds acting on multiple AD pathways. After simulated gastrointestinal digestion, peptide fractions P1 (GCAPR), P2 (QAGDQL), and P3 (AGDASVL) were assessed alongside phycocyanobilin (PCB) using molecular docking against Beta-secretase 1, Glycogen synthase kinase 3 beta, Acetylcholinesterase, and Butyrylcholinesterase. PCB showed strong affinities toward BChE (-10.0 kcal/mol) and GSK-3β (-8.4 kcal/mol), suggesting modulation of tauopathic and late-stage cholinergic pathways. P2 exhibited notable binding to AChE (-8.8 kcal/mol) and BACE1 (-7.6 kcal/mol), indicating effects on amyloidogenic and early cholinergic mechanisms, while P1 and P3 provided complementary moderate activity. Overall, these findings support further investigation of PBPs as potential sources of bioactive compounds for functional food and nutraceutical applications targeting AD-related pathways.
PMID:42637675 | DOI:10.1080/10799893.2026.2723004
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