6-hydroxy-nicotine on chlorisondamine-induced oxidative stress
and neurotoxicity: relevance for Alzheimer’s disease
- Research project financed by the Ministry of Education and Scientific Research - Executive Unit for Financing Higher Education, Research, Development and Innovation (UEFISCDI), contract no. 122/2015;
amount - 549.700
lei (aprox. 125 000 euros);
- Funding period - 2 years (1.10.2015 - 30.09.2017).
The search for neuroprotective therapeutics for Alzheimer’s disease (AD) has been recently geared toward the identification of modulators for nicotinic acetylcholine receptors (nAChR). Using computational methods, the Arthrobacter nicotinovorans metabolic intermediate 6-hidroxy-nicotine (6HNic) have been identified as a putative nAChR ligand. The cognitive-functions tests performed on normal rats showed that chemically synthesized 6HNic has positive effects on spatial memory, mainly by decreasing brain oxidative stress.The current research project aims to form a team with the goal to isolate 6HNic and to evaluate its potential of improving the cognitive and non-cognitive functions in a rodent model of AD. For this, the Arthrobacter nicotinovorans enzyme responsible for 6HNic production will be cloned, expressed, purified and further used to produce the compound in an in-vitro reaction. After its isolation by HPLC from the reaction mixture, 6HNic will be injected in chlorisondamine-treated rats and its neuroprotective and anti-oxidant properties will be assessed using a combination of behavioral tests, flow-cytometry and biochemistry techniques. Also, the systemic toxicity as well as pro-apoptotic properties will be investigated, in an attempt to fully characterize the compound and to conclude its applicability in the field of AD.
||Project coordinator, Biochemistry||More details...|
||Microbiology, Immunology||More details...|
||Neurophysiology, Behavior||More details...|
Project's objectives and activities:
- pdf file only in Romanian
List of publications:
1. Mihăşan, Marius, and Roderich Brandsch. 2016. “A Predicted T4 Secretion System and Conserved DNA- Repeats Identified in a Subset of Related Arthrobacter Plasmids.” Microbiological Research 191: 32–37 [Fulltext].
2. Hritcu Lucian, Ionita Radu, Motei Diana Elena, Babii Cornelia, Stefan Marius, Mihasan Marius. 2017. “Nicotine versus 6-Hydroxy-L-Nicotine against Chlorisondamine Induced Memory Impairment and Oxidative Stress in the Rat Hippocampus.” Biomedicine & Pharmacotherapy 86: 102–8. [Fulltext]
Submitted or under review:
Conferences and posters - full list as a pdf
file in romanian
Marius Mihăşan, PhD
Adress : Room B228, Biochemistry and Molecular Biology Laboratory, Faculty of Biology, Alexandru I Cuza University of Iasi, Carol I B-vd., No. 20A, Iaşi, 700506, Romania