Abstract

Background: Alzheimer’s disease (AD) is a progressive, multifactorial neurodegenerative disorder that is the main cause of dementia globally. AD is associated with increased oxidative stress, resulting from imbalance in production and clearance of reactive oxygen species (ROS). ROS can damage DNA and other macromolecules, leading to genome instability and disrupted cellular functions. Base excision repair (BER) plays a major role in repairing oxidative DNA lesions. Here, we compared the expression of BER components APE1, OGG1, PARP1 and Polβ in blood and postmortem brain tissue from patients with AD, mild cognitive impairment (MCI) and healthy controls (HC).

Results: BER mRNA levels were correlated to clinical signs and cerebrospinal fluid biomarkers for AD. Notably, the expression of BER genes was higher in brain tissue than in blood samples. Polβ mRNA and protein levels were significantly higher in the cerebellum than in the other brain regions, more so in AD patients than in HC. Blood mRNA levels of OGG1 was low and PARP1 high in MCI and AD.

Conclusions: These findings reflect the oxidative stress-generating energy-consumption in the brain and the importance of BER in repairing these damage events. The data suggest that alteration in BER gene expression is an event preceding AD. The results link DNA repair in brain and blood to the etiology of AD at the molecular level and can potentially serve in establishing novel biomarkers, particularly in the AD prodromal phase.

Abstract:

We report that the meningococcal pilus biogenesis protein PilG directly binds DNA in vitro and that thebinding is independent of the DNA uptake sequence (DUS). The affinity was mapped to the N-terminal amino acid residues 43 to 45. A reduction in DNA transformation was observed when PilG DNA binding was reduced by mutation of these residues, defining a biologically significant DNA binding domain. N-terminal PilG also interacts with the N-terminal region of PilQ, the major structural component of the pilus biogenesis machinery. These data suggest that PilG and PilQ in concert bind DNA during Type 4 pilus-mediated transformation.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0134954

Venue: The Norwegian Academy of Science and Letters (DNVA) in Oslo, Norway

We are delighted to announce that the Top Gear in Science 2015 (TGS2015) meeting now is open for registration.

Registration and payment by June 12 2015 using this link:
https://nettskjema.uio.no/answer/tgs2015.html

Registration fee: 490 NOK

For more information go to the "more" link.

 Time: June 4 2015 9 am - 4 pm
Venue: Domus Medica 4, L-200, University of Oslo, Norway

For registration please visit this link

Addendum: The NSSO2015 symposium was immediately fully booked.

Contact:

For more information please go to the "more" link below.

5th of Mars at 11:30 am at The Rotunda, Domus Medica 4

This is a unique seminar with the Olav Thon Foundation's International Research Awardees for Mathematics/Natural Science and Medicine 2015, Judith Campisi (Buck Institute for Research on Aging, USA) and Yossi Shiloh (Tel Aviv University, Israel). Our guest Vilhelm A. Bohr, NIH, will close the seminar with his talk.

Please see our program letter for more info, and for registration.

Link to the "Cradle of TB" seminar program