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.
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http://dx.doi.org/10.3390/pharmaceutics15041086 | DOI Listing |
Alzheimers Dement
December 2024
Neurology Department, Duke University, Durham, NC, USA
Background: APOE4 leads to increased neuroinflammation, neurocognitive decline, increased risk of Alzheimer’s disease, and may be associated with increased delirium risk. However, the safety and feasibility of pharmacologic modulation of APOE to prevent neuroinflammation and postoperative delirium is unclear.
Methods: We performed a Phase II, triple blind, escalating dose, randomized controlled trial to determine the safety, feasibility, and efficacy of the APOE mimetic peptide CN‐105 for preventing postoperative neuroinflammation and delirium.
Cell Rep
December 2024
Department of Neurodegenerative Diseases, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA. Electronic address:
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by extracellular amyloid plaques and neuronal Tau tangles. A recent study found that the APOE3 Christchurch (APOECh) variant could delay AD progression. However, the underlying mechanisms remain unclear.
View Article and Find Full Text PDFCardiovasc Diabetol
November 2024
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Background: Diabetic heart disease may eventually lead to heart failure, a leading cause of mortality in diabetic individuals. The lack of effective treatments for diabetes-induced heart failure may result from a failure to address the underlying pathological processes, including chronic, low-grade inflammation. Previous studies have reported that lipoxin A (LXA), known to promote resolution of inflammation, attenuates diabetes-induced atherosclerosis, but its impact on diabetic hearts has not been sought.
View Article and Find Full Text PDFInt Immunopharmacol
December 2024
The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou Province, PR China. Electronic address:
Apolipoprotein (Apo) E mimetic peptides down-regulate the inflammatory response and alleviate damage to secondary neurons after intracerebral hemorrhage (ICH). We designed a novel apoE receptor mimetic composed of the low-density lipoprotein receptor-associated protein-1 (LRP1) receptor-binding domain of apoE with 6 lysines (6KApoEp). The 6KApoEp peptide is small enough to penetrate the blood-brain barrier (BBB) and modulate the inflammatory response during damage to the central nervous system.
View Article and Find Full Text PDFJ Alzheimers Dis Rep
September 2024
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
Background: During Alzheimer's disease (AD) progression, there is a decline in the bioactive sphingolipid sphingosine-1-phosphate (S1P). Previous research showed that FTY720, an S1P mimetic, prevented cognitive decline and reduced ceramide levels in transgenic mice with familial AD carrying the human APOE4 gene (E4FAD) at 6-7 months of age.
Objective: The objective of this study is to explore the protective effects of FTY720 at late-stage AD.
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