Lipid participation in neuronal differentiation
 and neurodegenerative processes


Team of work

Falomir Lockhart, Lisandro
Principal Investigator
lysfalomir@yahoo.com.ar
Córsico, Betina
Investigator
bcorsico@med.unlp.edu.ar
Giménez, Ezequiel 
Research Fellow
eze.gmz4@gmail.com
Toscani, Andrés Martín
Research Fellow
amtoscani@gmail.com
León, Antonella
Dissertation Student
antonella.leon@outlook.com
Cabazzutti, Gian Franco
Dissertation Student
gianfrancocavazzutti@gmail.com
Carrero Riveros, Maria Alejandra
Dissertation Student
mariaalejandracarrero@gmail.com
   


Collaborators from other institutions

International

Jovin, Thomas M. 
Max Planck Institute für Biophysikalische Chemie, Göttingen, Alemania.

Outeiro, Tiago F. 
Georg-August-Universität Göttingen, Göttingen, Alemania.

Schüle, Birgitt 
The Parkinson's Institute and Clinical Center, Sunnyvale, CA, Estados Unidos.


National

Borsarelli, Claudio D. 
Centro de Investigaciones y Transferencia de Santiago del Estero, UNSE, Santiago del Estero, Argentina. 

Dántola, Laura 
Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas, Fac. de Cs. Exactas, UNLP, La Plata, Argentina. 

Giordano, Luciana 
Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman", Ciudad Autónoma de Buenos Aires, Argentina. 


Line overview

Neurodegenerative diseases are pathologic processes of growing concern. Parkinson´s Disease, for example, has a prevalence of near 2 % in the population above 65 years old. One can differentiate an idiopathic or senile, and a familial or early-onset forms. Different genetic and external factors converge and promote this disease, strongly associated to oxidative stress, mitochondrial function and the amiloide aggregation of the protein a-Synuclein (aSyn). This research line focuses in the study of the participation of lipids, mainly fatty acids, in different physiopathologic processes associated to Parkinson´s Disease, such as cellular differentiation, mitochondrial activity, lipid-mediated signal transduction in neurons and glial cells, immflamatory response in the brain, and expression and aggregation of aSyn.
In this project, we combine biophysicochemical, biochemical and cell biology study strategies, as well as the development fluorescent probes for the study of neuronal function. We plan to employ different cell lines. The incorporation of fibroblast and reprogrammed stem-cells from patients (with a molecular and clinical diagnose of Parkinson´s Disease) for confirming the most relevant results will allow us to mechanistically relate the genetic alterations with the triggering events of the neurodegenerative processes. The general aim of the project is to better understand the molecular events that trigger the Parkinson´s Disease and, in particular, elucidate the role of lipids in neurodegenerative diseases, in order to identify putative new strategies for early diagnosis and targets for therapeutic and prevention.

The work focuses around the proteins associated to Parkinson´s Disease, mainly aSyn, but also we will evaluate the expression and role of LRRK2, DJ-1, PINK, Parkin and GBA. Regarding the role of fatty acids, we will also pay attention to the Fatty Acid-Binding Proteins (FABPs), Free Fatty Acid Receptors (FFARs) and Peroxisome Proliferator-Activated Receptors (PPARs). These families of proteins mediate the signaling functions of fatty acids and their derivatives and had been associated to different neuronal pathologies.


Publications

  • Echinococcus granulosus Antigen B binds to monocytes and macrophages modulating cellresponse to inflammation. Parasites and vectors.
    Silva, V; Folle, A; Ramos. A; Kitano, E; Iwai, L; Corraliza, I; Córsico, B; Ferreira, A.
    2016. Londres: BIOMED CENTRAL LTD, vol. 9, n° 69, p. 1350-1357. ISSN 1756-3305

  • Elevated alphasynuclein caused by SNCA gene triplication impairs neuronal differentiation and maturation in Parkinson's patientderived induced pluripotent stem cells.
    Oliveira, L. M. A; Falomir Lockhart, L. J; Botelho, M. G; Lin, K-H; Wales, P; Koch, J; Gerhardt, E; Taschenberger, H; Outeiro, T. F; Lingor, P; Schuele, B; Arndt-Jovin, D. J; Jovin, T. M.
    2015.
    Cell Death and Disease. , Roma: Nature Publishing Group, vol. 6, n° 1994


  • Extracellular vesicle sorting of a-Synuclein is regulated by sumoylation.
    Kunadt, M; Eckermann, K; Stuendl, A; Gong, J; Russo, B; Strauss, K; Rai, S; Kügler, S; Falomir Lockhart, L; Schwalbe, M; Krumova, P; Oliveira, L. M. A; Bähr, M; Möbius, W; Levin, J; Giese, A; Kruse, N; Mollenhauer, B; Geiss-Friedlander, R; Ludolph, A. C; Freischmidt, A; Feiler, M. S; Danzer, K. M; Zweckstetter, M; Jovin, T. M; Simons, M; Weishaupt, J. H; Schneider, A.
    2015. Acta Neuropathologica. , Berlin: SPRINGER, vol. 129, p. 695-713. ISSN 0001-6322


  • Characterization of fatty acid binding and transfer from Δ98Δ, a functional all-β abridged form of IFABP. 
    Rodriguez Sawicki, L; Guerbi, M. X; Falomir Lockhart, L. J; Curto, L; Delfino, J.M; Córsico, B; Franchini, G. R. 
    2014. Biochimica et Biophysica acta-molecular and cell biology of lipids. , Amsterdam: ELSEVIER SCIENCE BV,. vol. 1841, p. 1733-1740. ISSN 1388-1981
  • Higher vulnerability and stress sensitivity of neuronal precursor cells carrying an alpha-synuclein gene triplication. 
    Flierl, A; Oliveira, L. M. A; Falomir Lockhart, Lisandro J.; Mak, Sally; Hesley, Jayne; Soldner, Frank; Arndt-Jovin, Donna J.; Jaenisch, Rudolf ; Langstom, J. William ; Jovin, Thomas M.; Schuele, Birgitt . 
    2014. Plos one. , San Francisco: PUBLIC LIBRARY SCIENCE,. vol. 9, n° 11, ISSN 1932-6203
  • IFABP portal region insertion during membrane interaction depends on phospholipid composition.
    De Gerónimo, E; Rodriguez Sawicki, L; Bottasso, N; Franchini, G. R; Zamarreño, F; Costabel, M. D; Córsico, B; Falomir.Lockhart, L. J. 
    2014. Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids. , Amsterdam: ELSEVIER SCIENCE BV, 2014 - . vol. 1841, p. 141-150. ISSN 1388-1981
  • Biophysical properties and cellular toxicity of covalent cross-linked oligomers of α-synuclein formed by photoinduced side-chain tyrosyl radicals. 
    Borsarelli, C. D; Falomir Lockhart, L. J; Ostatná, V; Fauerbach, J. A; Hsiao, H. H; Urlaub, H; Palecek, E; Jares Erijman, E. A; Jovin, T. M. 
    2012. Free Radic Biol Med 53(4):1004-1015
  • Specificity and kinetics of α-Synuclein binding to model membranes determined with fluorescent ESIPT probe.
    Shvadchak, V. V; Falomir Lockhart, L. J; Yushchenko, D. A; Jovin, T. M.
    2011. J Biol Chem 286(15):13023-32


  • Interactions of a-Synuclein with Lipids and Artificial Membranes Monitored by ESIPT Probes. 
    Shvadchak, V. V; Falomir Lockhart, L. J; Yushchenko, D. A; Jovin, T. M. 
    2011. Lipids and Cellular Membranes in Amyloid Disease. Editor: Raz Jelinek. Wiley-VCH, 2011


Book - Book chapters

  • Análisis estructural y funcional de macromoléculas. 
    Córsico, B; Falomir-Lockhart, L. J; Franchini, G. R; Scaglia, N. 
    2013. La Plata. Libro de Catedra. Edulp, p. 422. ISBN 978-950-34-1057-8
  • Microscopía Óptica.
    Falomir Lockhart, L. J; Fuentes, F; Córsico, B; Franchini, G. R; Scaglia, N. 
    2013. Capítulo 13. Microscopía Óptica. La Plata: EDULP, 2013. p. 365-416. ISBN 978-950-34-1057-8
  • Fluorescencia. 
    De Gerónimo, E; Falomir Lockhart, L. J; Córsico, B; Franchini, Gr; Scaglia, N.
    2013. Capítulo 2. Fluorescencia. La Plata: EDULP, 2013. p. 39-77. ISBN 978-950-34-1057-8
  • Interaccion Proteina Proteina. 
    Rodriguez Sawicki, L; Bottasso, N; Córsico, B; Franchini, G; Falomir Lockhart, L. J; Scaglia, N. 
    2013. La Plata: EDULP, 2013. p. 299-342

Awards

  • “Premio mejor trabajo”
    6th Lipid Binding Protein Society Meeting. Vancouver, Canada. 2007. 
    Sterol carrier protein from Yarrowia lipolytica transfers fatty acids to acceptor membranes through a collision-mediated mechanism. 
    Falomir Lockhart, L. J; Burgardt, N. I; Ferreyra, R. G; Ceolin, M; Ermácora, M. R; Córsico, B.





INIBIOLP - Instituto de Investigaciones Bioquímicas de La Plata "Profesor Doctor Rodolfo R. Brenner"
Consejo Nacional de Investigaciones Científicas y Técnicas - Facultad de Ciencias Médicas - U.N.L.P.
Avenida 60 y 120 - C.P. 1900 La Plata - Prov. de Buenos Aires - Argentina. Tel. 54-221-4824894 - Fax. 54-221-4258988 - E-mail :