Exploring the therapeutic efficacy of peptides in ameliorating Alzheimer's disease.

Alzheimer's disease (AD) is one of the neurodegenerative disorders, the hallmarks of which include deposits of extracellular beta-amyloid (Aβ) as well as intracellular tau neurofibrillary tangles (NFTs) tangles. With disease progression, neuronal apoptosis combined with cerebral atrophy occurs, leading to cognitive impairment and long-term memory loss. Recently, species have been identified as a functional food and are being explored for the prevention of various diseases widely studied to prevent or treat many neurodegenerative diseases. Hence, we for the first time investigated the neuroprotective effects of short-chain peptides (CPPs) i.e. <1 kDa, 1-3 kDa, 3-10 kDa, and >10 kDa on the and neuronal injury models. Our results showed that CPP with a molecular weight of 1-3 kDa and 3-10 kDa could elevate the survival rate of Aβ or l-Glutamic acid-injured N2A cells. These treatments also inhibited Aβ and tau NFTs in N2A cells and prevented progressive neuronal cellular damage by suppressing inflammatory cytokines such as PGE2, iNOS, IL-6, TNF-α, COX-2, IL-1β, TGF-β1, and NF-κB. Further, our Aβ-induced AD mice model demonstrated that 1-3 kDa or 3-10 kDa CPP could improve spatial cognition and learning memory. We also observed a decreased cell loss ratio in CA1-CA3 hippocampal regions. Taken together, our findings imply that CPPs may exert their anti-AD impact through anti-inflammatory, and anti-amyloid activities via reducing APP and tau NFT.