Cell Biology

A brief overview of the project

Neurodegenerative diseases are currently a major health issue and a topic for a research priority at the global level. Thus, neuro-degenerative diseases occur commonly in adults over the age of 65, you are responsible for disability in progressive and irreversible, and is a burden on the socio-economic significance. To date, there is no therapeutic intervention has merit or good argument to stop it or to slow the progression of these diseases, only symptomatic therapies, the benefits of the net, but it is often low. The results of the clinical trials, and recent experimental, have shown the existence of a possible causal link between the different features of the composition of the gut microbiota, and neuro-degenerative diseases, in particular Parkinson's disease. The substrate of these causal link is mediated both by the individual products of the microbiota (e.g., the amyloid protein function, biosurfactants, endotoxin), as well as of the endogenous proteins whose expression may be modulated/drug-induced microbiotă (for example, calprotectina is an inflammatory marker but also a protein and a potential amiloidogenă). Also, the dysfunction that occurs between the host and the microbiota of the intestine (dysbiosis with inflammation of the gut) could produce changes in neuronal favorable neurodegenerării (for example, changes to the side-effects of the alteration of the intestinal barrier and/or blood-brain barrier, or as a result of the disruption to the axis of the microbiotă-gut-brain oxidative stress, dysfunction of the mitochondrial etc). All of these aspects have not been investigated so far, in more detail, and is a research topic of interest.

Project objective:

The characterization of the effect of the proteins of the bacterial amyloid, functional, and other products amiloidogene of the gut microbiota on the aggregation of pathological proteins, and the propagation of the pathology of a pattern in the prionic in models of neurodegeneration, in order to identify new biomarkers and target molecules, the development of strategies of prevention, and of personalized therapies in Parkinson's disease, sporadically also in other neurodegenerative diseases, thus contributing to the improvement of the approach of having a major impact on your health. 

The objectives of the project:

1. The development and improvement of the protocol for the test and/or immuno-dose standard of the product amiloidogene the bacteria of interest. 
2. The evaluation of the association between the fecal of the product amiloidogeni bacterial agents of interest, the level of the calprotectinei the feces, and the Parkinson's disease-phase motor is an early study on the analytical, observational, case-control. 
3. The confirmation of the results on the association between the fecal of the product amiloidogeni the bacterial level of the calprotectină, and Parkinson's disease, testing for possible associations with other proteinopatii are affected. 
4. The characterization of the effects of the by-products amiloidogeni you have the gut microbiota associated with disease, Parkinson's disease at the stage of motor and early calprotectină on the aggregation and internalization/propagation of alpha-sinucleinei, in vitro, cell lines, and in the presence and absence of the rotenonei . 
5. The evaluation of the effect of the by-products amiloidogeni you have the gut microbiota associated with disease, Parkinson's disease, calprotectină, and short-chain fatty acids on clinical manifestations, pathology of the gut and the pathology of the brain in vivo models of proteins for the diagnosis of Parkinson's disease in terms of microbiotă the gut of wild, by using protocols that are based on the results of in vitro studies. 
6. The evaluation of the effect of the by-products amiloidogeni you have the gut microbiota associated with disease, Parkinson's disease, calprotectinei and of short chain fatty acids on clinical manifestations, pathology of the gut and the pathology of the brain in models of proteins for the diagnosis of Parkinson's disease in terms of microbiotă of the gut is controlled using the protocols on the basis of the results of the previous one. 
7. The evaluation of the effect of the by-products amiloidogeni of the gut microbiota (selected on the basis of the results of the previous), the calprotectinei of fatty acids with short-chain on the cell lines and the patterns of the proteins to other neurodegenerative diseases that involves the folding of the poor, and the aggregation of pathological proteins. 
8. The development of a model of incidence on the involvement of the protein amiloidogene bacterial infection, and other products amiloidogeni you have the gut microbiota and the calprotectinei in the diagnosis of Parkinson's disease by means of extrapolation from the Alzheimer's disease and other proteinopatii are affected.

Expected results:

1. biomarkers of streptococci to the stage of the engine's early stages of Parkinson's disease – may be a biomarker of microbiotă, or which are mixed, the host-microbiotă.
2. biomarkers of streptococci to the stage of the engine's early stages of Parkinson's disease confirmed on a different group of patients, and to have a specific, known in comparison with other neurodegenerative diseases. 
3. experimental paradigm is optimized for the assessment of the effects of the by-products of intestinal microbiota, and other molecules on the aggregation, the internalization and propagation of alpha-sinucleinei under different experimental conditions. 
4. the model etiopatogen an intermediary for Parkinson's disease/Alzheimer's disease on the causal relationship between the exposure of the products to amiloidogene bacterial aggregation is a pathological alpha-sinucleinei, and the spread of the model prionic of the gut to the brain. 
5. murine model, optimized for the study of gut microbiota in Parkinson's disease. 
6. the model etiopatogen on the involvement of the protein amyloid in functional bacterial infection, and other products amiloidgeni you have the gut microbiota in the aggregation of pathological proteins, and in the propagation of the model prionic of pathology in Parkinson's disease, found in Alzheimer's disease and other neurodegenerative diseases involving abnormal protein.
7. the list of targets for the molecular potential interventions/strategies in the therapeutic prevention of custom, or to stop/slow the progression of neurodegenerative diseases, which are identified in the framework of the project.

Delivery:

Communication social sciences

• • A. C. Smith – The bacteria and neurodegeneration (Bacteria and neurodegeneration) – a National Conference on Alzheimer's disease And 2019, Bucharest, Romania, on February 2019, oral presentation
  • B. Popescu – Gastrointestinal dysmotility is the major cause of motor fluctuations in PD (host of the debate) – The 13th World Congress on Controversies in Neurology (CONy), Madrid, Spania, aprilie 2019 – oral presentation
  • B. Popescu – Are microbiota reasonable targets in the therapy of neurodegenerative diseases? – YES – The 13th World Congress on Controversies in Neurology (CONy), Madrid, Spania, aprilie 2019 – oral presentation
  • Laura Dumitrescu, Daciana Marta, Emilia Manole, Adela Danau, Antonia Lefter, Laura Cristina Ceafalan, Mihaela Gherghiceanu, Bogdan Ovidiu Popescu – Intestinal barrier integrity, bacterial endotoxin exposure and inflammation markers in Parkinson’s disease. Annual Scientific Meeting of Victor Babes Institute; The 12th National Pathology Symposium, November 21-23, 2019, Bucharest, Romania oral presentation

• Laura Dumitrescu, Daciana Marta, Adela Danau, Antonia Lefter, Delia Tulba, Liviu Cozma, Emilia Manole, Mihaela Gherghiceanu, Laura Cristina Ceafalan, Bogdan Ovidiu Popescu – Intestinal inflammation and intestinal barrier integrity markers in sporadic Parkinson’s disease, International Pathology Conference of “Victor Babes” Institute, Bucharest, Romania, 4-6 November, 2021, Modern Medicie, Supplement 1/2021:60, oral presentation

• Bogdan Ovidiu Popescu – Microbiota and neurodegenerative diseases, International Pathology Conference of “Victor Babes” Institute, Bucharest, Romania, 4-6 November, 2021, Modern Medicie, Supplement 1/2021:37, oral presentation
• Emilia Manole, Gisela Gaina, Oana Mosoia, Alexandra Bastian, Laura Ceafalan – The two different faces of Interleukin-6, as a myokine and as a cytokine. International Pathology Conference of “Victor Babes” Institute, Bucharest, Romania, 17-19 November, 2022, oral presentation

Publications

1. Octavian Ioghen, Emilia Manole, Mihaela Gherghiceanu, Bogdan O. Popescu, Laura Cristina Ceafalan, Non-Myelinating Schwann cells in health and disease. In Demyelination disorders, Cap. 4, Ed. Emeritus Prof. Stavros Baloyannis, Fabian H. Rossi, Welwin Liu, 2020, IntechOpen, ISBN: 978-1-83968-654-2, Print ISBN: 978-1-83968-653-5.
2. Emilia Manole, Alexandra Bastian, Ana Maria Oproiu, Monica Teodora Neagu, Carolina Constantin, Gheorghita Izvoranu, Schwann cell plasticity in peripheral nerve regeneration after injury. In Demyelination disorders, Cap. 3, Ed. Emeritus Prof. Stavros Baloyannis, Fabian H. Rossi, Welwin Liu , 2020, IntechOpen, ISBN: 978-1-83968-654-2, Print ISBN: 978-1-83968-653-5.
3. Laura C. Ceafalan, Maria Dobre, Elena Milanesi, Andrei M. Niculae, Emilia Manole, Mihaela Gherghiceanu, Mihail E. Hinescu, Gene expression profile of adhesion and extracellular matrix molecules during early stages of skeletal muscle regeneration, Journal of Cellular and Molecular Medicine. 2020; 24(17): 10140–10150. IF 5.295
4. Emilia Manole, Laura Dumitrescu, Cristina Niculite, Bogdan Ovidiu Popescu, Laura Cristina Ceafalan, Potential roles of functional bacterial amyloid proteins,bacterial biosurfactants and other putative gut microbiota-products in the etiopatho-geny of Parkinson’s Disease, BIOCELL 2021, 45(1), 1-16. IF you 1.110
5. E Manole, C Niculite, IM Lambrescu, G Gaina, O Ioghen, LC Ceafalan, ME Hinescu, Macrophages and Stem Cells-Two to Tango for Tissue Repair? Biomolecules 2021;11(5):697 IF 6.064
6. Laura Dumitrescu, Daciana Marta, Adela Danau, Antonia Lefter, Delia Tulba, Liviu Cozma, Emilia Manole, Mihaela Gherghiceanu, Laura Cristina Ceafalan,  Bogdan Ovidiu Popescu, Serum and fecal markers of intestinal inflammation and intestinal barrier permeability are elevated in Parkinson’s disease, Frontiers in Neuroscience Vol 15, Art. nr. 689726 IF 5.152
7. Emilia Manole, Gisela Gaina, Laura Cristina Ceafalan, Mihail Eugen Hinescu, Skeletal muscle stem cells in aging: asymmetric/symmetric divisions switching, Symmetry, 2022, 14, 2676. IF 2.7