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Review
. 2023 Mar 28;15(4):1086.
doi: 10.3390/pharmaceutics15041086.

ApoE Mimetic Peptides to Improve the Vicious Cycle of Malnutrition and Enteric Infections by Targeting the Intestinal and Blood-Brain Barriers

Reinaldo B Oriá  1 , Raul S Freitas  1 , Cássia R Roque  1 , José Carlos R Nascimento  1   2 , Ana Paula Silva  3 , João O Malva  3 , Richard L Guerrant  4 , Michael P Vitek  5
Affiliations
Review

ApoE Mimetic Peptides to Improve the Vicious Cycle of Malnutrition and Enteric Infections by Targeting the Intestinal and Blood-Brain Barriers

Reinaldo B Oriá et al. Pharmaceutics. .

Abstract

Apolipoprotein E (apoE) mimetic peptides are engineered fragments of the native apoE protein's LDL-receptor binding site that improve the outcomes following a brain injury and intestinal inflammation in a variety of models. The vicious cycle of enteric infections and malnutrition is closely related to environmental-driven enteric dysfunction early in life, and such chronic inflammatory conditions may blunt the developmental trajectories of children with worrisome and often irreversible physical and cognitive faltering. This window of time for microbiota maturation and brain plasticity is key to protecting cognitive domains, brain health, and achieving optimal/full developmental potential. This review summarizes the potential role of promising apoE mimetic peptides to improve the function of the gut-brain axis, including targeting the blood-brain barrier in children afflicted with malnutrition and enteric infections.

Keywords: apoE mimetic peptides; blood-brain barrier; environmental enteric dysfunction; gut-brain axis; intestinal inflammation; malnutrition.

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Conflict of interest statement

The authors declare no conflict of interest. M. P. Vitek is a principal in Cognosci, Inc., which has ownership rights to selected apoE-mimetic peptides.

Figures

Figure 1
Figure 1
Overview of the vicious cycle of malnutrition and enteric infections (even without diarrhea) early in life. Complex interactions of contaminated environments, gut microbiota dysbiosis, and the hosts genome/epigenome may lead to lasting health effects, including intestinal barrier breakdown and inflammation, poor immune responses against enteric pathogens, and circulating gut born LPS to the brain during critical times of development with cognitive/behavioral impairments. If chronic and persistent, this vicious cycle could increase the risk for cardiovascular and neurodegenerative diseases later in life. In-place continuous interventions, including access to potable water, sanitation, vaccines, and healthy diets, are needed to ameliorate and possibly reverse such deleterious effects. Figure created with BioRender.com.
Figure 2
Figure 2
(A) Selected ApoE mimetic peptides (COG 133 and COG144) with beneficial effects in different models of intestinal and CNS injury. (B) ApoE mimetic peptides could improve IEC-6 and IEC-18 (murine crypt intestinal cell line) cell monolayer recovery with more Wnt-βcatenin and less β-catenin degradation complex (AXIN and APC) mRNA transcription and intestinal mucositis-driven inflammation following 5-Fluorouracil (5-FU) challenge. TJ = tight junctions, BBB = blood-brain barrier, SH = stroke hemorrhage. APC = adenomatous polyposis coli. Arrow up = increase and arrow down = decrease. Figure created with BioRender.com.
Figure 3
Figure 3
Schematic outline of the most beneficial effects of the apoE mimetic peptides based on preclinical models to support the potential use of these compounds to remediate the environmental enteric dysfunction-related outcomes. Arrow up = increase and arrow down = decrease. Figure created with BioRender.com.
Figure 4
Figure 4
(A) Summary of apoE mimetic peptides beneficial effects on the blood-brain barrier (BBB) in models of brain injury. (B) The assessment of novel in vitro models of BBB and brain organoids may help to elucidate whether selected apoE peptides could be beneficial in preserving the gut-brain axis of mice afflicted with malnutrition/enteric infections. Figure created with BioRender.com.
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