Alexandru Ioan Cuza University of Iasi
Effects of 6-hydroxy-nicotine on chlorisondamine-induced oxidative stress and neurotoxicity: relevance for Alzheimers disease
The Executive Agency for Higher Education, Research, Development and Innovation Funding (UEFISCDI)
The search for neuroprotective therapeutics for Alzheimers 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.