Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Helicobacter Pylori Urease: Potential Contributions to Alzheimer’s Disease

Version 1 : Received: 11 January 2022 / Approved: 13 January 2022 / Online: 13 January 2022 (15:37:01 CET)

How to cite: Uberti, A.F.; Callai-Silva, N.; Grahl, M.V.C.; Piovesan, A.R.; Nachtigall, E.G.; Furini, C.R.G.; Carlini, C.R. Helicobacter Pylori Urease: Potential Contributions to Alzheimer’s Disease. Preprints 2022, 2022010194 (doi: 10.20944/preprints202201.0194.v1). Uberti, A.F.; Callai-Silva, N.; Grahl, M.V.C.; Piovesan, A.R.; Nachtigall, E.G.; Furini, C.R.G.; Carlini, C.R. Helicobacter Pylori Urease: Potential Contributions to Alzheimer’s Disease. Preprints 2022, 2022010194 (doi: 10.20944/preprints202201.0194.v1).

Abstract

Alzheimer’s disease (AD) causes dementia and memory loss in the elderly. Deposits of beta-amyloid peptide and hyperphosphorylated tau protein are present in AD’s brain. A filtrate of Helicobacter pylori’s culture was previously found to induce hyperphosphorylation of tau in vivo, suggesting that bacterial exotoxins could permeate the blood brain barrier and directly induce tau’s phosphorylation. H. pylori, which infects ~60% of the world population and causes gastritis and gastric cancer, produces a pro-inflammatory urease (HPU). Here the neurotoxic potential of HPU was investigated in cultured cells and in rats. SH-SY5Y neuroblastoma cells exposed HPU (50-300 nM) produced reactive oxygen species (ROS) and had an increased [Ca2+]i. HPU-treated BV-2 microglial cells produced ROS, cytokines IL-1β and TNF-α, expressed Iba1 and showed reduced viability, consistent with a neurotoxic effect of HPU. Rats received daily i.p. HPU (5 µg) for 7 days. Hyperphosphorylation of tau at Thr205, Ser199 and Ser396 sites was seen in hippocampal homogenates of treated rats, with no alterations in total tau or GSK-3b levels. HPU was not detected in the brain homogenates. Behavioral tests were performed to assess cognitive impairments. Our findings support previous data suggesting an association between infection by H. pylori and tauopathies such as AD, possibly mediated by its urease.

Keywords

Helicobacter pylori; urease; neuroinflammation; tau hyperphosphorylation; pro-inflammatory cytokines; object recognition test; elevated plus maze; SH-SY5Y neuroblastoma cells; BV-2 microglia

Subject

LIFE SCIENCES, Biochemistry

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.