Helicobacter pylori Urease: Potential Contributions to Alzheimer's Disease
Augusto F Uberti1, Natalia Callai-Silva1, Matheus V C Grahl1
1Laboratory of Neurotoxins, Brain Institute of Rio Grande do Sul (BRAINS) and Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre CEP 90610-000, RS, Brazil.
International Journal of Molecular Sciences
|March 25, 2022
Summary
Helicobacter pylori urease (HPU) may contribute to Alzheimer's disease (AD) by inducing tau hyperphosphorylation and neuroinflammation. This study investigated HPU's neurotoxic effects in cells and rats, linking it to AD-like pathology.
Area of Science:
- Neuroscience
- Microbiology
- Pathology
Background:
- Alzheimer's disease (AD) is characterized by tau protein hyperphosphorylation.
- Helicobacter pylori infection is increasingly linked to neurodegenerative diseases.
- H. pylori produces urease (HPU), a potential neurotoxic agent.
Purpose of the Study:
- To investigate the neurotoxic potential of H. pylori urease (HPU).
- To determine if HPU can induce tau hyperphosphorylation and neuroinflammation in vitro and in vivo.
- To explore the association between H. pylori infection and tauopathies like AD.
Main Methods:
- Cultured SH-SY5Y neuroblastoma and BV-2 microglial cells were exposed to HPU.
- Rats received daily intraperitoneal injections of HPU.
- Biochemical analyses (tau phosphorylation, GSK-3β levels, Iba1 expression) and behavioral tests were performed.
Main Results:
- HPU induced reactive oxygen species (ROS), increased intracellular calcium ([Ca2+]i) in neuroblastoma cells, and reduced viability in microglial cells.
- HPU treatment in rats led to tau hyperphosphorylation at specific sites (Ser199, Thr205, Ser396) and microglial activation in the hippocampus.
- No alterations in total tau or GSK-3β levels were observed, and HPU was not detected in brain homogenates.
Conclusions:
- H. pylori urease (HPU) exhibits neurotoxic properties, inducing tau hyperphosphorylation and neuroinflammation.
- These findings support a potential mechanism linking H. pylori infection to tauopathies, including Alzheimer's disease.
- HPU may mediate the association between H. pylori and AD pathogenesis, possibly without direct brain entry.
Related Concept Videos
01:16Treating Helicobacter pylori in Peptic Ulcers: Antimicrobial Therapy
595
Helicobacter pylori, a resilient gram-negative bacterium, can thrive in the stomach's harsh, acidic environment. Infection with H. pylori leads to a cascade of events within the stomach lining. One of the critical disruptions caused by this bacterium is the interference with somatostatin production, a hormone responsible for regulating acid secretion. This interference tips the balance, escalating acid secretion and diminishing bicarbonate levels. This imbalance compromises the defensive...
595
01:24Pathophysiology of Peptic Ulcer Disease: Mucosal Defense Factors
636
Peptic ulcer disease, commonly called PUD, represents a multifaceted condition characterized by disruptions in the lining of the gastrointestinal (GI) tract. Central to the protection of the gastrointestinal lining is the mucosal-bicarbonate barrier. This physiological defense mechanism is a formidable shield against the corrosive effects of gastric acid and pepsin secretion in the stomach. Its role is pivotal in maintaining the structural integrity of the stomach's inner lining.
636
01:30Peptic Ulcer Disease I: Introduction
313
Peptic Ulcer Disease (PUD) is characterized by mucosal excavation in the esophagus, stomach, pylorus, or duodenum. It can manifest as acute or chronic based on the extent and duration of mucosal involvement.
An acute ulcer, marked by superficial erosion and minimal inflammation, swiftly resolves upon identifying and addressing the underlying cause. In contrast, a chronic ulcer persists, potentially eroding through the muscular wall and forming fibrous tissue.
Peptic ulcers can also be...
An acute ulcer, marked by superficial erosion and minimal inflammation, swiftly resolves upon identifying and addressing the underlying cause. In contrast, a chronic ulcer persists, potentially eroding through the muscular wall and forming fibrous tissue.
Peptic ulcers can also be...
313
01:22Pathophysiology of Peptic Ulcer Disease: Injurious Factors
758
Peptic ulcers are sores on the stomach's inner lining and the upper small intestine, which are the result of disruptions in the mucosal layer that houses parietal cells which produce gastric acid, and chief cells which secrete pepsinogen.
In the antrum region, G cells secrete the gastrin hormone that binds to gastrin-cholecystokinin-B (CCK2) receptors on parietal and enterochromaffin-like (ECL) cells in the fundic glands. Simultaneously, the vagus nerve releases acetylcholine, which binds...
In the antrum region, G cells secrete the gastrin hormone that binds to gastrin-cholecystokinin-B (CCK2) receptors on parietal and enterochromaffin-like (ECL) cells in the fundic glands. Simultaneously, the vagus nerve releases acetylcholine, which binds...
758
01:26Alzheimer's Disease: Overview
709
Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
709
01:22Alzheimer's Disease: Treatment
276
Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
276