Lipid participation in neuronal differentiation and neurodegenerative processes

Team of work

Principal InvestigatorFalomir

Falomir Lockhart, Lisandro

Investigator
lfalomir@med.unlp.edu.ar

Giménez, Ezequiel Gimenez

Research Fellow
egimenez@med.unlp.edu.ar

Collaborators from other institutions

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

Outeiro, Tiago F.
Department of Neurodegeneration and Restorative Research, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center Göttingen, Göttingen, Alemania.

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

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.

Analysis of pyrene-labelled apolipoprotein A-I oligomerization in solution: Spectra deconvolution and changes in P-value and excimer formation.
Tárraga, Wilson A.; Falomir-Lockhart, Lisandro J.; Garda, Horacio A.; González, Marina C.
2021. Archives of biochemistry and biophysics: ELSEVIER SCIENCE INC,- . vol. 699, ISSN 0003-9861

Dataset on pyrene-labelled apolipoprotein A-I, model development and fitting to monitor oligomeric species of its lipid-free form.
Tarraga W; Garda H. A; Falomir Lockhart L; Gonzalez M. C.
2021. Data in brief: Elsevier, 2021 - . vol. 13, n° 35, ISSN 2352-3409

Fatty acid signaling mechanisms in neural cells: Fatty acid receptors. Frontiers in celular neuroscience.
Falomir-Lockhart, Lisandro Jorge; Cavazzutti, Gian Franco; Giménez, Ezequiel; Toscani, Andrés Martín.
2019: Frontiers Media S.A.,vol. 13, ISSN 1662-5102
doi.org/10.3389/fncel.2019.00162

Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells.
Sampayo, R. G; Toscani, A. M; Rubashkin, M. G; Thi, K; Masullo, L. A; Violi, I. L; Lakins, J. N; Cáceres, A; Hines, W. C; Leskow, F. C; Stefani, F. D; Chialvo, D. R; Bissell, M. J; Weaver, V. M; Simian, M.
2018. Journal of cell biology. ROCKEFELLER UNIV PRESS, vol. 217, n° 8, p. 2777-2798. ISSN 0021-9525

FABP1 knockdown in human enterocytes impairs proliferation and alters lipid metabolism.
Rodriguez Sawicki, L; Bottasso Arias, N. M; Scaglia, N; Falomir Lockhart, L; Franchini, G. R; Storch, J; Córsico, B.
2017. Biochimica et biophysica acta-molecular and cell biology of lipids. ELSEVIER SCIENCE BV. vol. 1862, n° 12, p. 1587-1594. ISSN 1388-1981

Distinct ErbB2 receptor populations differentially interact with beta1 integrin in breast cancer cell models.
Toscani, M; Sampayo, R; Barabas, F; Fuentes, F; Simian, M; Coluccio Leskow, F.
2017. Plos one. San Francisco: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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 α-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 α-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

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

“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.




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