BrainMap

LUCIAN HRITCU

Profesor univ. dr. habil.

Professor - UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Teaching staff

Web of Science ResearcherID: G-5378-2010

Curriculum Vitae (07/10/2025)

Expertise & keywords

Antiaggregation potential of 6-hydroxy-L-nicotine from Paenarthrobacter nicotinovorans pAO1 against amyloid peptide: in vitro and in vivo studies Call name: P 4 - Proiecte de cercetare exploratorie - PCE-2021
PN-III-P4-PCE-2021-1692 2022 - 2024

Role in this project: Project coordinator

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://cercetare.bio.uaic.ro/grupuri/bioactive/content/grants/PCE2022_hl.html

Abstract:

Alzheimer's disease (AD) is characterized by progressive degradation of memory processes, being associated with three major changes that occur in the brain: i) the formation of intra- and extracellular beta-amyloid deposits; ii) the appearance of neurofibrillary tangles and iii) the death of cholinergic neurons and a significant decrease in acetylcholine level. The identification of neuroprotective therapies for AD was dominated by the hypothesis of amyloid cascade and tau proteins. Unfortunately, both approaches have so far failed to provide an effective therapeutic strategy. The involvement of α7 and α4β2 subtypes of nicotinic receptors (nAChRs) in the pathogenesis of AD has led to the proposal of a new therapeutic approach. Immunohistochemical studies in the brains of patients with sporadic AD have shown that Aβ1-42 and α7nAChR are present in neuritic plaques and this interaction may be inhibited by α7nAChRs ligands. Nicotine, through its ability to bind to nAChRs is the ideal molecule for the development of new derivatives with therapeutic applications. The project aims to test the antiaggregating potential against Aβ1-42 of 6-hydroxy-L-nicotine (6HLN), derived from the metabolism of nicotine in the microorganism Paenarthrobacter nicotinovorans pAO1. To achieve this goal, the project activities will focus on evaluating the action of 6HLN in vitro on cell lines and in vivo on 5xFAD transgenic mice, in order to identify its therapeutic potential.

Steps towards an Arthrobacter nicotinovorans biotechnology for neuro-pharmaceuticals production Call name: P 1 - SP 1.1 - Proiecte de cercetare pentru stimularea tinerelor echipe independente
PN-III-P1-1.1-TE-2016-0367 2019 - 2020

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://www.bio.uaic.ro/cercetare/grupuri/bioactive/content/grants/te2019.html

Abstract:

6-hidroxy-nicotine (6HNic), a naturally occurring metabolite of Arthrobacter nicotinovorans was shown to bind the nicotinic acetylcholine receptors and to modulate their function. Experimental tests using laboratory rats have demonstrated the ability of 6HNic to cope with the acetylcholine depletion and to restore normal brain functions. 6HNic has been thereby identified as a high impact bio-pharmaceutical with application in the therapy of neurodegenerative disorders associated with low acetylcholine levels.

6HNic is produced in our group by using a genetically engineered strain of Arthrobacter nicotinovorans. The cultivation conditions currently employed allow for a yield of approx. 50 mg 6HNic / 100 ml culture. This is enough for common in-vitro and in-vivo lab test, but not near sufficient for the large scale test required for establishing the real therapeutic potential of 6HNic. The scope of the funding application is to develop a technology for high-yield production of the neuroprotective agent 6HNic using high-density cultures in a bio-fermenter. For this, a genetically engineered Arthrobacter strain will be created by knocking-out specific genes using suicidal vectors. The mutant strain will be further accommodated to a bio-reactor and the conditions for optimum 6HNic production will be evaluated. The final goal is to formulate an high-yield Arthrobacter based method for the production of 6HNic which would allow our group to further deepen the study of nicotine derivatives applications in biotechnology.

Steps towards an Arthrobacter nicotinovorans biotechnology for neuro-pharmaceuticals production Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2016-0177 2017 - 2018

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://www.bio.uaic.ro/cercetare/grupuri/bioactive/content/grants/ped2017.html

Abstract:

6-hidroxy-nicotine (6HNic), a naturally occurring metabolite of Arthrobacter nicotinovorans was shown to bind the nicotinic acetylcholine receptors and to modulate their function. Experimental tests using laboratory rats have shown the ability of 6HNic to cope with the acetylcholine depletion and to restore normal brain functions. 6HNic has been thereby identified as a high impact bio-pharmaceutical with application in the therapy of neurodegenerative disorders associated with low acetylcholine levels. The scope of the funding application is to develop a technology for the production of the neuroprotective agent 6HNic in an industrial-like environment and to test it at a pilot scale. For this, a genetically engineered Arthrobacter strain will be created by knocking-out specific genes using suicidal vectors. The mutant strain will be further accommodated to a bio-reactor and the conditions for optimum 6HNic production will be evaluated. The final goal is to formulate a microbial based biotechnology for the production of 6HNic ready to be transferred to the industrial environment.

Effects of 6-hydroxy-nicotine on chlorisondamine-induced oxidative stress and neurotoxicity: relevance for Alzheimer’s disease Call name: Projects for Young Research Teams - RUTE -2014 call
PN-II-RU-TE-2014-4-0106 2015 - 2017

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation:

Project website: http://www.bio.uaic.ro/cercetare/grupuri/bioactive/content/grants/te2015.html

Abstract:

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 funding application aims to form a young 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.

The characterization of pathophysiological protein modifications by bio-affinity mass spectrometric methods Call name: Projects for Young Research Teams - RUTE -2014 call
PN-II-RU-TE-2014-4-0920 2015 - 2017

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation:

Project website: https://teclu.chem.uaic.ro/brindusapetre

Abstract:

All pathophysiological disorders from neurodegenerative diseases to diabetes, heart diseases, cancer and rare diseases are characterized by damage in structure or function of essential biological macromolecules (e.g. peptides, proteins and enzymes). The proposed research project comprises two major objectives: (i), Neurological Abeta peptide involved in Alzheimer’s disease (AD) and the effect of oxidative stress will be investigated by structural mass spectrometry (MS) in combination with bioaffinity strategies. The major interest is to obtain detailed understanding of oxidative Abeta aggregation mechanism, investigating toxic oligomeric species formed in the initial step of this process. Synthetic nitrated Abeta peptides will be used for identification, characterization and quantification of oligomers in AD mouse models. (ii), Moreover we propose to start developing new mass spectrometric based approaches for early diagnostic of treatable rare diseases. Lysosomal storage diseses (LSD’s) are a large group of rare metabolic disorders caused by the deficiency of single enzymes in metabolizing biopolymer substrates. Synthetic substrates for a few defected lysosomal enzymes will be synthesized and used for fluorimetric and mass spectrometric based diagnostic approaches. Together our data will improve the quality of methods and will increase further research interest regarding intrigue parallels existing between pathology of AD and lysosomal Niemann-Pick rare disorder.

FILE DESCRIPTION	DOCUMENT
List of research grants as project coordinator or partner team leader	Download (223.6 kb) 22/11/2019
Significant R&D projects for enterprises, as project manager
R&D activities in enterprises
Peer-review activity for international programs/projects