Παληκαράς Κωνσταντίνος, Επικ. Καθηγητής

 

Tο ερευνητικό αντικείμενο 

 

Η ερευνητική μονάδα «Νευρογενετικής και Γήρανσης» υπάγεται στο Εργαστήριο Πειραματικής Φυσιολογίας «Φυσιολογείον» της Ιατρικής Σχολής του Εθνικού και Καποδιστριακού Πανεπιστημίου Αθηνών (ΕΚΠΑ). Ο κεντρικός στόχος των ερευνητικών μας προσπαθειών είναι η διερεύνηση των μοριακών μηχανισμών που διέπουν τη λειτουργία του νευρικού συστήματος. Στο εργαστήριο μας χρησιμοποιούμε το νηματώδη Caenorhabditis elegans (Εικόνα 1) ως οργανισμό μοντέλο για να κατανοήσουμε τους μοριακούς μηχανισμούς λειτουργίας του νευρικού συστήματος.

 

Το νευρικό σύστημα του νηματώδη αποτελείται από μόλις 302 νευρώνες γεγονός που προσφέρει μια μοναδική πλατφόρμα ιδανική για τη μελέτη των πολύπλοκων νευρωνικών δικτύων. Παρά το μινιμαλιστικό νευρικό του σύστημα, ο νηματώδης C. elegans, εμφανίζει μεγάλη ποικιλία αισθητικών ικανοτήτων και συμπεριφορών. Τέτοιο ευρύ φάσμα ευδιάκριτων φαινοτύπων μπορεί να αξιοποιηθεί χρησιμοποιώντας εργαλεία εξελιγμένης γενετικής, οπτογενετικής, μοριακής βιολογίας καθώς και σύγχρονων μεθόδων μικροσκοπίας, ώστε να διασαφηνιστούν οι μοριακοί μηχανισμοί που διέπουν την κυτταρική ομοιόσταση. Πάνω σε αυτά τα εξαιρετικά χαρακτηριστικά, χτίζουμε τις μελέτες μας, εστιάζοντας στους μηχανισμούς ελέγχου ποιότητας των μιτοχονδρίων και το πως αυτοί επηρεάζουν την ομοιόσταση των κυττάρων και των διαφορετικών ιστών του οργανισμού (Εικόνα 2). Επιπλέον, τα ενδιαφέροντά μας περιλαμβάνουν 1. την ανακάλυψη νέων φυτικών και συνθετικών χημικών ενώσεων που διατηρούν την λειτουργία των μιτοχονδρίων κατά τη γήρανση, 2. Την μελέτη των μοριακών μηχανισμών που ρυθμίζουν τον νευροεκφυλισμό και τη γήρανση, 3., την ανάπτυξη μοντέλων νευροεκφυλιστικών ασθενειών στον C. elegans, και 4. την ανάπτυξη νέων γενετικών εργαλείων για την έρευνα του νηματώδη.

 

PUBLICATIONS

 

Selected publications:

  1. Xie C., Zhuang X., Niu Z., Ai R., Lautrup S., Zheng S., Jiang Y., Han R., SenGupta T., Cao S., Lagartos-Donate M., Cai C., Xie L., Caponio D., Wan W., Schmauck-Medina T., Zhang J., Wang H., Lou G., Xiao X., Zheng W., Palikaras K., Yang G., Caldwell K., Cladwell G., Shen H., Nilsen H., Lu J., Fang EF. Amelioration of Alzheimer’s disease pathology by mitophagy inducers identified via machine learning and cross-species workflow. Nature Biomedical Engineering, 2022; doi: 1038/s41551-021-00819-5
  2. Aman Y., Schmauck-Medina T., Hansen M., Morimoto RI., Simon AK., Bjedov I., Palikaras K., Simonsen A., Johansen T., Tavernarakis N., Rubinsztein DC., Patridge L., Kroemer G., Labbadia J. and Fang EF. Autophagy in healthy aging and disease. Nature Aging, 2021; doi: 1038/s43587-021-00098-4
  3.  
  4. Zaninello M.*, Palikaras K.*, Sotiriou A., Tavernarakis N. and Scorrano L. Sustained intracellular calcium rise mediates neuronal mitophagy in models of autosomal dominant optic atrophy. Cell Death and Differentiation, 2021 *equal contribution; doi: 1038/s41418-021-00847-3
  5. SenGupta T.*, Palikaras K.*, Esbensen Y.Q., Konstantinidis G., Galindo FJN., Achanta K., Kassahun H., Stavgiannoudaki I., Bohr VA., Akbar M., Gaare J., Tzoulis C., Tavernarakis N. and Nilsen H. Base excision repair causes age-depedent accumulation of single-stranded DNA breaks that contribute to Parkinson disease pathology. Cell Reports, 2021*equal contribution; doi: 1016/j.celrep.2021.109668
  6. Palikaras K.*, Achanta K., Choi S., Akbari M.* and Bohr VA.* Alteration of mitochondrial homeostasis is an early event in a elegans model of human tauopathy. Aging (Albany NY), 2021 *corresponding authors; doi: 10.18632/aging.203683
  7. Zaninello M., Palikaras K., Naon D., Iwata K., Herkenne S., Quintana-Cabrera R., Semenzato M., Grespi F., Ross-Cisneros F., Carelli V., Sadun A., Tavernarakis N. and Scorrano L. Inhibition of autophagy curtails visual loss in a model of autosomal dominant optic atrophy. Nature Communications, 2020; 1038/s41467-020-17821-1
  8. Lou G.*, Palikaras K.*, Lautrup S.*, Schneibye-Knudsen M., Tavernarakis N. and Fang E.F. Mitophagy and neuroprotection. Trends in Molecular Medicine, 2019 *equal contribution; doi: 1016/j.molmed.2019.07.002
  9. Fang EF.*, Hou Y.*, Palikaras K.*, Adriaanse BA., Kerr JS., Yang B., Lautrup S., Hasan-Olive M., Caponio D., Dan X., Rocktäschel P., Croteau DL., Akbari M., Greig NH., Fladby T., Nilsen H., Cader MZ., Mattson MP., Tavernarakis N., Bohr VA. Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease. Nature Neuroscience, 2019 *equal contribution; doi: 1038/s41593-018-0332-9
  • Palikaras K., Lionaki E. and Tavernarakis N. Mechanisms of mitophagy in cellular homeostasis, physiology and pathology. Nature Cell Biology, 2018; doi: 1038/s41556-018-0176-2
  • Palikaras K., Lionaki E. and Tavernarakis N. Coordination of mitophagy and mitochondrial biogenesis during ageing in elegans. Nature, 2015; doi: 10.1038/nature14300
  • Schiavi Maglioni S., Palikaras K., Shaik A., Strapazzon F., Brinkmann V., Torgovnick A., Castelein N., De Henau S., Braeckman BP., Cecconi F., Tavernarakis N., Natascia Ventura N. Iron-starvation-induced mitophagy mediates lifespan extension upon mitochondrial stress in C. elegans. Current Biology, 2015; doi: 10.1016/j.cub.2015.05.059

 

Research and methods publications:

  • Xie C., Zhuang X., Niu Z., Ai R., Lautrup S., Zheng S., Jiang Y., Han R., SenGupta T., Cao S., Lagartos-Donate M., Cai C., Xie L., Caponio D., Wan W., Schmauck-Medina T., Zhang J., Wang H., Lou G., Xiao X., Zheng W., Palikaras K., Yang G., Caldwell K., Cladwell G., Shen H., Nilsen H., Lu J., Fang EF. Amelioration of Alzheimer’s disease pathology by mitophagy inducers identified via machine learning and cross-species workflow. Nature Biomedical Engineering, 2022; doi: 1038/s41551-021-00819-5
  • Palikaras K.*, SenGupta T., Nilsen H., Tavernarakis N.* Assessment of dopaminergic neuron degeneration in a C. elegans model of Parkinson’s disease. STAR Protocols, 2022 *corresponding authors; doi: 1016/j.xpro.2022.101264
  • Zaninello M.*, Palikaras K.*, Sotiriou A., Tavernarakis N. and Scorrano L. Sustained intracellular calcium rise mediates neuronal mitophagy in models of autosomal dominant optic atrophy. Cell Death and Differentiation, 2021 *equal contribution; doi: 1038/s41418-021-00847-3
  • SenGupta T.*, Palikaras K.*, Esbensen Y.Q., Konstantinidis G., Galindo FJN., Achanta K., Kassahun H., Stavgiannoudaki I., Bohr VA., Akbar M., Gaare J., Tzoulis C., Tavernarakis N. and Nilsen H. Base excision repair causes age-depedent accumulation of single-stranded DNA breaks that contribute to Parkinson disease pathology. Cell Reports, 2021*equal contribution; doi: 1016/j.celrep.2021.109668
  • Palikaras K.*, Achanta K., Choi S., Akbari M.* and Bohr VA.* Alteration of mitochondrial homeostasis is an early event in a elegans model of human tauopathy. Aging (Albany NY), 2021 *corresponding authors; doi: 10.18632/aging.203683
  • Zaninello M., Palikaras K., Naon D., Iwata K., Herkenne S., Quintana-Cabrera R., Semenzato M., Grespi F., Ross-Cisneros F., Carelli V., Sadun A., Tavernarakis N. and Scorrano L. Inhibition of autophagy curtails visual loss in a model of autosomal dominant optic atrophy. Nature Communications, 2020; 1038/s41467-020-17821-1
  • Papandreou M.*, Palikaras K.* and Tavernarakis N.* Assessment of de novo protein synthesis rates in Caenorhabditis elegans. Journal of Visualized Experiments, 2020 *equal contribution; doi: 3791/61170
  • Palikaras K.* and Tavernarakis N.* Modeling age-associated neurodegenerative diseases in Caenorhabditis elegans. Journal of Visualized Experiments, 2020 *corresponding authors; doi: 3791/61169.
  • Fang EF.*, Hou Y.*, Palikaras K.*, Adriaanse BA., Kerr JS., Yang B., Lautrup S., Hasan-Olive M., Caponio D., Dan X., Rocktäschel P., Croteau DL., Akbari M., Greig NH., Fladby T., Nilsen H., Cader MZ., Mattson MP., Tavernarakis N., Bohr VA. Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease. Nature Neuroscience, 2019 *equal contribution; doi: 1038/s41593-018-0332-9
  • Palikaras K., Lionaki E. and Tavernarakis N. Mitophagy dynamics in Caenorhabditis elegans. Methods in Molecular Biology, 2019; doi: 1007/978-1-4939-8873-0_43
  • Fang EF., Palikaras K., Sun N., Fivenson EM., Spangler RD., Kerr JS., Cordonnier SA., Hou Y., Dombi E., Kassahun H., Tavernarakis N., Poulton J., Nilsen H., Bohr VA. In vitro and in vivo detection of mitophagy in human cells, elegans and mice. Journal of Visualized Experiments, 2017; doi: 10.3791/56301
  • Palikaras K. and Tavernarakis N. Assessing mitochondria selective autophagy in the nematode Caenorhabditis elegans. Methods in Molecular Biology, 2017; doi: 1007/978-1-4939-6824-4_21
  • Palikaras K., Mari M., Petanidou B., Pasparaki A, Filippidis G. and Tavernarakis N. Ectopic fat deposition contributes to age-associated pathology in Caenorhabditis elegans. Journal of Lipid Research, 2017; doi: 1194/jlr.M069385
  • Palikaras K. and Tavernarakis N. In vivo mitophagy monitoring in Caenorhabditis elegans to determine mitochondrial homeostasis. Bio-protocol, 2017; doi: 21769/BioProtoc.2215
  • Palikaras K. and Tavernarakis N. Measuring oxygen consumption rate in Caenorhabditis elegans. Bio-protocol, 2016; doi: 21769/BioProtoc.2049
  • Palikaras K. and Tavernarakis N. Intracellular Assessment of ATP Levels in Caenorhabditis elegans. Bio-protocol, 2016; doi: 21769/BioProtoc.2048
  • Palikaras K., Lionaki E. and Tavernarakis N. Coordination of mitophagy and mitochondrial biogenesis during ageing in elegans. Nature, 2015; doi: 10.1038/nature14300
  • Schiavi Maglioni S., Palikaras K., Shaik A., Strapazzon F., Brinkmann V., Torgovnick A., Castelein N., De Henau S., Braeckman BP., Cecconi F., Tavernarakis N., Natascia Ventura N. Iron-starvation-induced mitophagy mediates lifespan extension upon mitochondrial stress in C. elegans. Current Biology, 2015; doi: 10.1016/j.cub.2015.05.059
  • Taferner A., Pircher H., Koziel R., von Grafenstein S., Baraldo G., Palikaras K., Liedl K. R., Tavernarakis N. and Jansen-Duerr P. FAH domain containing protein 1 (FAHD-1 is required for mitochondrial function and locomotion activity in elegans. PLos ONE, 2015; doi: 10.1371/journal.pone.0134161
  • Mari M., Filipidis G., Palikaras K., Petanidou B., Fotakis K., Tavernarakis N. Imaging ectopic fat deposition in Caenorhabditis elegans muscles using non-linear microscopy. Microscopy Research and Technique, 2015; doi: 1002/jemt.22504
  • Morselli E., Maiuri M. C., Markaki M., Megalou E., Pasparaki A., Palikaras K., Galluzzi L., Criollo A., Malik S. A., Madeo F., Tavernarakis N. and Kroemer G. Caloric restriction and resveratrol prolong longevity via the sirtuin-1 mediated induction of autophagy. Cell Death and Disease, 2010; doi: 1038/cddis.2009.8

 

Reviews:

  • Borbolis F. and Palikaras K. The compartmentalized nature of neuronal mitophagy: molecular insights and implications. Experts Reviews in Molecular Medicine, 2022; doi: 1017/erm.2022.31
  • Charmpilas N., Fang E.F., Palikaras K. Mitophagy and neuroinflammation: a compelling interplay.

Current Neuropharmacology, 2022 *corresponding author; doi: 10.2174/1570159X20666220628153632

  • Aman Y., Schmauck-Medina T., Hansen M., Morimoto RI., Simon AK., Bjedov I., Palikaras K., Simonsen A., Johansen T., Tavernarakis N., Rubinsztein DC., Patridge L., Kroemer G., Labbadia J. and Fang EF. Autophagy in healthy aging and disease. Nature Aging, 2021; doi: 1038/s43587-021-00098-4
  • Doxaki C., Papadopoulou E., Maniadaki I., Tsakalis N., Palikaras K. and Vorgia P. Intracranial hypertension secondary to Guillain-Barre Syndrome: A Case Report and Literature Review. Frontiers in Pediatrics, 2021; doi: 3389/fped.2020.608695
  • Doxaki C and Palikaras K.* Neuronal Mitophagy: Friend or Foe? Frontiers in Developmental and Cell Biology, 2021 *corresponding author; doi: 3389/fcell.2020.611938
  • Palikaras K. and Tavernarakis N. Regulation and roles of mitophagy at synapses. Mechanisms of Ageing and Development, 2020; doi: 1016/j.mad.2020.111216
  • Lou G.*, Palikaras K.*, Lautrup S.*, Schneibye-Knudsen M., Tavernarakis N. and Fang E.F. Mitophagy and neuroprotection. Trends in Molecular Medicine, 2019 *equal contribution; doi: 1016/j.molmed.2019.07.002
  • Palikaras K., Lionaki E. and Tavernarakis N. Mechanisms of mitophagy in cellular homeostasis, physiology and pathology. Nature Cell Biology, 2018; doi: 1038/s41556-018-0176-2
  • Markaki M.*, Palikaras K.* and Tavernarakis N. Novel insights into the anti-aging role of mitophagy. International Review of Cell and Molecular Biology, 2018 *equal contribution; doi: 1016/bs.ircmb.2018.05.005
  • Gkikas I.*, Palikaras K.* and Tavernarakis N. The role of mitophagy in innate immunity. Frontiers in Immunology, 2018 *equal contribution; doi: 3389/fimmu.2018.01283
  • Palikaras K., Daskalaki I., Markaki M. and Tavernarakis N. Mitophagy and age-related pathologies: Development of new therapeutics by targeting mitochondrial turnover. Pharmacology and Therapeutics, 2017; doi: 1016/j.pharmthera.2017.04.005
  • Lionaki E.*, Markaki M.*, Palikaras K.* and Tavernarakis N. Mitochondria, autophagy and age-associated neurodegenerative diseases: New insights into a complex interplay. Biochimica et biophysica Acta – Bioenergetics, 2015 *equal contribution; doi: 1016/j.bbabio.2015.04.010
  • Palikaras K., Lionaki E., Tavernarakis N. Mitophagy: in sickness and in health. Molecular and Cellular Oncology; 2015; doi: 1080/23723556.2015.1056332
  • Palikaras K., Lionaki E., Tavernarakis N. Interfacing mitochondrial biogenesis and elimination to enhance host pathogen defense and longevity. Worm, 2015; doi: 1080/21624054.2015.1071763
  • Palikaras K., Lionaki E., Tavernarakis N. Balancing mitochondrial biogenesis and mitophagy to maintain energy metabolism homeostasis. Cell Death and Differentiation, 2015; doi: 1038/cdd.2015.86
  • Palikaras K., Lionaki E., Tavernarakis N. Coupling mitogenesis and mitophagy for longevity. Autophagy, 2015; doi: 1080/15548627.2015.1061172.
  • Palikaras K. and Tavernarakis N. Mitochondrial homeostasis: The interplay between mitophagy and mitochondrial biogenesis. Experimental Gerontology, 2014; doi: 1016/j.exger.2014.01.021
  • Nikoletopoulou V., Markaki M., Palikaras K. and Tavernarakis N. Crosstalk between apoptosis, necrosis and autophagy. Biochimica et Biophysica Acta-Molecular Cell Research, 2013; doi: 1016/j.bbamcr.2013.06.001
  • Palikaras K. and Tavernarakis N. Mitophagy in neurodegeneration and ageing. Frontiers in Genetics, 2012; doi: 3389/fgene.2012.00297
  • Morselli E., Maiuri M. C., Markaki M., Megalou E., Pasparaki A., Palikaras K., Criollo A., Galluzzi L., Malik S. A., Vitale I., Michaud M., Madeo F., Tavernarakis N. and Kroemer G. The life span-prolonging effect of sirtuin-1 is mediated by autophagy. Autophagy, 2010; doi: 4161/auto.6.1.10817

 

Book chapters

  1. Palikaras K. and Tavernarakis N. (2020) Mitophagy Encyclopedia of Molecular Pharmacology (Stefan Offermanns, Walter Rosenthal, editors), Springer Major Reference Works, Heidelberg, Germany
  2. Palikaras K., Princz A. and Tavernarakis N. (2018) Mitophagy modulators. Encyclopedia of Biomedical Gerontology (Suresh Rattan, editor), Elsevier Inc., San Diego, USA
  3. Mari M., Petanidou B., Palikaras K., Fotakis C., Tavernarakis N., and Filippidis G. (2015) Non-linear imaging techniques visualize the lipid profile of elegans. In Advanced Microscopy Techniques IV; and Neurophotonics II (Emmanuel Beaurepaire, Peter T. C. So, Francesco Pavone, and Elizabeth M. Hillman, editors), SPIE Press, Bellingham, USA.
  4. Palikaras K. and Tavernarakis N. (2015) Multiphoton fluorescence light microscopy. In eLS: Citable reviews in the life sciences (Jose M. Valpuesta, editor), Wiley-Blackwell, London, UK.
  5. Palikaras    and   Tavernarakis   N.   (2013)   Caenorhabditis   elegans (Nematode). In Brenner’s Encyclopedia of Genetics (2nd edition; Stanley Maloy and Kelly Hughes, editors), Academic Press, San Diego, USA.
  6. Palikaras K. and Tavernarakis N. (2012) Multiphoton fluorescence light microscopy. In eLS: Citable reviews in the life sciences (Jose M. Valpuesta, editor), Wiley-Blackwell, London, UK.

 

FUNDING

 

Μέλη της ερευνητικής ομάδας «Νευρογενετικής και γήρανσης»

Παληκαράς Κωνσταντίνος

 

Δρ. Φοίβος Μπορμπόλης, kmpormpol@med.uoa.gr

Δρ. Χριστίνα Δοξάκη, cdoxaki@med.uoc.gr

 

Κατερίνα Κιτοπούλου, aikitop@med.uoa.gr

Ρούσσος Αντώνης

 

Ειρήνη Μυτιληναίου, eirinimyt20@gmail.com

Παναγιώτα Μυλιώτη, panmilioti@gmail.com