Impact of Peptide Transport and Memory Function in the Brain

Abstract

Recent studies have reported the benefits of food-derived peptides for memory dysfunction. Beyond the physiological effects of peptides, their bioavailability to the brain still remains unclear since the blood-brain barrier (BBB) strictly controls the transportation of compounds to the brain. Here, updated transportation studies on BBB transportable peptides are introduced and evaluated using in vitro BBB models, in situ perfusion, and in vivo mouse experiments. Additionally, the mechanisms of action of brain health peptides in relation to the pathogenesis of neurodegenerative diseases, particularly Alzheimer's disease, are discussed. This discussion follows a summary of bioactive peptides with neuroprotective effects that can improve cognitive decline through various mechanisms, including anti-inflammatory, antioxidative, anti-amyloid β aggregation, and neurotransmitter regulation.

Keywords: Alzheimer’s disease; bioavailability; blood-brain barrier; cognitive impairment; dementia; peptide.

Figure 1

Schematic structure of the BBB. The walls of all brain capillaries consist of a thin monolayer of specialized brain microvascular endothelial cells connected by tight junctions (TJs). These endothelial cells are surrounded by a vascular basement membrane (BM), pericytes, parenchymal BM, and astrocyte endfeet, all of which directly or indirectly contribute to the barrier function of the BBB.

Figure 2

Transport routes across the BBB. The transportation routes include paracellular diffusion, transcellular diffusion, carrier-mediated transport, receptor-mediated transcytosis, and adsorptive transcytosis. Paracellular diffusion is an energy-independent pathway that occurs between epithelial cells, and transcellular diffusion occurs through epithelial cells. Carrier-mediated transport pathway is mediated by the transporter proteins expressed on the luminal and/or abluminal side of the brain capillary endothelial cells. Receptor-mediated transcytosis is an energy-dependent pathway involving the binding of the ligand and the receptor, endocytosis, transcytosis, and exocytosis of transported molecules. Adsorptive transcytosis is a receptor-independent endocytosis process driven by electrostatic interactions between positively charged peptides and the negatively charged surfaces of BMECs.

Figure 3

Transportability of peptides across the BBB. (A) Schematic representation of the in vitro reconstituted BBB model. Endothelial cells are seeded on the upper side of the filter, astrocytes are seeded at the bottom of the plates, and pericytes at the filter membranes of inverted cell culture inserts. (B) Representative in situ brain perfusion experiments. After the mice were anesthetized, the descending thoracic aorta was ligated, and at the start of the perfusion, the left jugular was sectioned. After perfusion, the whole brain was removed from the mice and used for detection. (C) Schematic representation of in vivo animal experiments. The mouse or rat is administrated with target peptides, then the brain was collected and finally detected by the radioactive tracing technique or mass spectroscopy techniques.