In vitro transcytosis of Helicobacter pylori histidine-rich protein through gastric epithelial-like cells and the blood–brain barrier

2021 ◽  
Author(s):  
Takashi Iwasaki ◽  
Aiki Maruyama ◽  
Yurika Inui ◽  
Toshihiko Sakurai ◽  
Tsuyoshi Kawano
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Helicobacter Pylori ◽  
Disease Progression ◽  
Blood Brain Barrier ◽  
Gastric Epithelium ◽  
Brain Barrier ◽  
Blood Brain ◽  
H Pylori

Abstract Recent epidemiological studies have supported the correlation between Helicobacter pylori infection and the development of Alzheimer's disease. HpHpn, a histidine-rich H. pylori protein, forms amyloid-like oligomers; it may be a pathogenic factor for Alzheimer's disease progression. HpHpn may also be transported from the gastric epithelium to the brain. However, HpHpn is secreted from H. pylori on the outer surface of gastric epithelia; therefore, the hypothesized movement of HpHpn across the gastric epithelium to the blood remains controversial. Here, we found the HpHpn showed acidic pH-dependent cellular uptake and subsequent secretion in human gastric epithelial-like carcinoma cells. Furthermore, HpHpn exhibited in vitro permeability across the blood–brain barrier. Although further in vivo experiments are required, our findings suggest that in vitro transcytosis of HpHpn in gastric epithelial cells and the blood–brain barrier may provide new insights into the correlation between H. pylori infections and Alzheimer's disease progression.

Do Periodontal Pathogens or Associated Virulence Factors Have a Deleterious Effect on the Blood-Brain Barrier, Contributing to Alzheimer’s Disease?

2021 ◽  
pp. 1-17
Author(s):  
Mhd Ammar Kouki ◽  
Anna Barlach Pritchard ◽  
Jane Elizabeth Alder ◽  
StJohn Crean
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Virulence Factors ◽  
Current Knowledge ◽  
Brain Barrier ◽  
Periodontal Pathogens ◽  
Blood Brain

The central nervous system (CNS) is protected by a highly selective barrier, the blood-brain barrier (BBB), that regulates the exchange and homeostasis of bloodborne molecules, excluding xenobiotics. This barrier forms the first line of defense by prohibiting pathogens from crossing to the CNS. Aging and chronic exposure of the BBB to pathogens renders it permeable, and this may give rise to pathology in the CNS such as Alzheimer’s disease (AD). Researchers have linked pathogens associated with periodontitis to neuroinflammation and AD-like pathology in vivo and in vitro. Although the presence of periodontitis-associated bacteria has been linked to AD in several clinical studies as DNA and virulence factors were confirmed in brain samples of human AD subjects, the mechanism by which the bacteria traverse to the brain and potentially influences neuropathology is unknown. In this review, we present current knowledge about the association between periodontitis and AD, the mechanism whereby periodontal pathogens might provoke neuroinflammation and how periodontal pathogens could affect the BBB. We suggest future studies, with emphasis on the use of human in vitro models of cells associated with the BBB to unravel the pathway of entry for these bacteria to the CNS and to reveal the molecular and cellular pathways involved in initiating the AD-like pathology. In conclusion, evidence demonstrate that bacteria associated with periodontitis and their virulence factors are capable of inflecting damage to the BBB and have a role in giving rise to pathology similar to that found in AD.

P2-264: Oxysterols, Blood-Brain Barrier (BBB) and Alzheimer's Disease: in vitro studies on endothelial cells and pericytes

2011 ◽  
Vol 7 ◽  
pp. S396-S397
Author(s):  
Julien Saint-Pol ◽  
Elodie Vandenhaute ◽  
Marie-Christine Boucau ◽  
Lucie Dehouck ◽  
Roméo Cecchelli ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
In Vitro Studies ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals Highly Stabilized Curcumin Nanoparticles Tested in an In Vitro Blood–Brain Barrier Model and in Alzheimer’s Disease Tg2576 Mice

2012 ◽  
Vol 15 (2) ◽  
pp. 324-336 ◽  
Author(s):  
Kwok Kin Cheng ◽  
Chin Fung Yeung ◽  
Shuk Wai Ho ◽  
Shing Fung Chow ◽  
Albert H. L. Chow ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Curcumin Nanoparticles ◽  
Blood Brain ◽  
Blood Brain Barrier Model ◽  
Barrier Model ◽  
Tg2576 Mice

scholarly journals Preformulation Studies of a Stable PTEN-PDZ Lipopeptide Able to Cross an In Vitro Blood-Brain-Barrier Model as a Potential Therapy for Alzheimer’s Disease

2020 ◽  
Vol 37 (10) ◽  
Author(s):  
Aikaterini Lalatsa ◽  
Yujiao Sun ◽  
Jose Ignacio Gamboa ◽  
Shira Knafo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Cell Permeability ◽  
Brain Barrier ◽  
Blood Brain ◽  
Blood Brain Barrier Model ◽  
Bbb Permeability ◽  
Barrier Model

Abstract Purpose Amyloid β (Aβ) drives the accumulation of excess Phosphatase and Tensin Homolog Deleted on Chromosome 10 (PTEN) at synapses, inducing synaptic depression and perturbing memory. This recruitment of PTEN to synapses in response to Aβ drives its interaction with PSD95/Disc large/Zonula occludens-1 (PDZ) proteins and, indeed, we previously showed that an oligo lipopeptide (PTEN-PDZ) capable of blocking such PTEN:PDZ interactions rescues the synaptic and cognitive deficits in a mouse model of Alzheimer’s disease. Hence, the PTEN:PDZ interaction appears to be crucial for Aβ-induced synaptic and cognitive impairment. Here we have evaluated the feasibility of using PTEN-PDZ lipopeptides based on the human/mouse PTEN C-terminal sequence, testing their stability in biological fluids, their cytotoxicity, their ability to self-assemble and their in vitro blood-brain barrier (BBB) permeability. Myristoyl or Lauryl tails were added to the peptides to enhance their cell permeability. Methods Lipopeptides self assembly was assessed using electron microscopy and the thioflavin T assay. Stability studies in mouse plasma (50%), intestinal washing, brain and liver homogenates as well as permeability studies across an all human 2D blood-brain barrier model prepared with human cerebral endothelial cells (hCMEC/D3) and human astrocytes (SC-1800) were undertaken. Results The mouse lauryl peptide displayed enhanced overall stability in plasma, ensuring a longer half-life in circulation that meant there were larger amounts available for transport across the BBB (Papp0-4h: 6.28 ± 1.85 × 10−6 cm s−1). Conclusion This increased availability, coupled to adequate BBB permeability, makes this peptide a good candidate for therapeutic parenteral (intravenous, intramuscular) administration and nose-to-brain delivery. Graphical Abstract

scholarly journals β-Amyloid Protein Induces Mitophagy-Dependent Ferroptosis Through the CD36/PINK/PARKIN Pathway Leading to Blood-Brain Barrier Destruction in Alzheimer's Disease

2021 ◽  
Author(s):  
li Jianhua ◽  
Li mengyu ◽  
Ge Yangyang ◽  
Chen Jiayi ◽  
Ma Jiamin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanism ◽  
Blood Brain Barrier ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Blood Brain ◽  
Bbb Permeability

Abstract Background Blood-brain barrier (BBB) dysfunction may occur in the onset of Alzheimer's disease (AD). While pericytes are a vital part of the neurovascular unit and the BBB, acting as the gatekeeper of the BBB. Amyloid β (Aβ) deposition and neurofibrillary tangles in the brain are the central pathological features of AD. CD36 promotes vascular amyloid deposition and leads to vascular brain damage, neurovascular dysfunction, and cognitive deficits. However, the molecular mechanism in destroying pericytes of the BBB are still unclear. Objectives To investigate the effect of low-dose Aβ1-40 administration on pericyte outcome and BBB injury molecular mechanism. Methods We selected 6-month-old and 9-month-old APP/PS1 mice and wild-type (WT) mice of the same strain, age, and sex as controls. We assessed the BBB by PET/CT. Brain pericytes were extracted and cocultured with endothelial cells (bEnd.3) to generate an in vitro BBB model to observe the effect of Aβ1-40 on the BBB. Furthermore, we explored the intracellular degradation and related molecular mechanisms of Aβ1-40 after being engulfed in cells through CD36. Results BBB permeability and the number of pericytes decreased in APP/PS1 mice. Aβ1-40 increases the permeability of the BBB in an in vivo model and downregulates the expression of CD36, which reversed the Aβ-induced changes in BBB permeability. Aβ1-40 was phagocytized in pericytes with high expression of CD36. We observed that this molecule inhibited pericyte proliferation, caused mitochondrial damage, and increased mitophagy. Finally, we confirmed that Aβ1-40 induced pericyte mitophagy-dependent ferroptosis through the CD36/PINK1/Parkin pathway. Conclusions PDGFRβ (a marker of pericytes), CD36, and amyloid β colocalized in vitro and in vivo and that Aβ1-40 caused BBB destruction by upregulating the expression of CD36 in pericytes. The mechanism by which Aβ1-40 destroys the BBB involves induction of pericyte mitophagy-dependent ferroptosis through the CD36/PINK1/Parkin pathway.

scholarly journals A first-principles study on potential chelation agents and indicators of Alzheimer's disease

RSC Advances ◽  
2020 ◽  
Vol 10 (58) ◽  
pp. 35574-35581
Author(s):  
Bryan Wang ◽  
Xuan Luo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Serum ◽  
Blood Brain Barrier ◽  
First Principles ◽  
Brain Barrier ◽  
Serum Transferrin ◽  
Human Serum Transferrin ◽  
First Principles Study ◽  
Blood Brain

Human-serum transferrin is involved in the transportation of aluminum across the blood–brain barrier.

Sign in / Sign up

Export Citation Format

Share Document