Kjell Fuxe
Anknuten till Forskning
To understand the communication modes and the molecular integrative mechanisms in the brain that make possible the operation of the neural-glial networks involved in mental and neurological disorders
Om mig
Jag har arbetat med att förstå kommunikation och integration i hjärnans neuronala-gliala nätverk. Denna forskning har givit bevis för existensen av centrala DA, NA and serotonin neuron, volym transmission i dess olika former, och receptor-receptor interaktioner i heteroreceptor komplex i centrala nervsystemet. Jag använde denna kunskap till att utveckla nya strategier för behandling av kokain addiktion, schizofreni, depression och Parkinson's sjukdom.
Denna forskning ledde till att vi kunde utveckla DA receptor agonister för behandling av Parkinson's sjukdom och bidraga med signifikanta insatser inom molekylär neuropsykofarmakologi. Integration av signaler från synaptisk transmission och volymtransmission kunde äga rum via synaptiska och extrasynaptiska komplex vilket representerade en ny viktig mekanism för modulering av synapser. Vår hypotes var att reorganisationen av homo-och heteroreceptor komplex i det postsynaptiska membranet kan representera den molekylära basen för inlärning och minne. De nya heteroreceptor komplex som vi upptäckte tycks representera nya mål för behandling av kokainaddiktion, schizofreni, depression och Parkinson's sjukdom.
Läs mer om vår forskning på Fuxe and Borroto-Escuela laboratory.
Forskningsbeskrivning
Konceptet över allosteriska receptor-receptor interaktioner i G protein kopplade receptor (GPCR) innehållande homo-och heteroreceptor komplex, i vilka de interagerar direkt med varandra, ger en ny dimension till begreppet molekylär integration i hjärnan. Receptor-receptor interaktioner förändrar på ett dynamiskt sätt receptorernas bindning av sin trans- mittor , samt deras farmakologi, signalering och internalisering och sålunda deras funktion. Vi har introducerat hypotesen att vulnerabiliteten hos distinkta heteroreceptor komplex kan vara en viktig orsak till flera av hjärnans sjukdomar genom avsevärda förändringar i deras mängd och allosteriska receptor-receptor interaktioner.
Summary of recent work in the lab:
I- Concepts introduced by our group on GPCR heteroreceptor complexes and their integrative receptor-receptor interactions in the CNS for understanding brain integration and providing novel treatments of brain disease (https://pubmed.ncbi.nlm.nih.gov/28270751/)
II- Understanding integrative molecular mechanisms involving especially adenosine (A2AR)- dopamine (D2R) heteroreceptor complexes and their receptor-receptor interactions but also MOR-D2likeR heteroreceptor complexes. It will help elucidate cocaine and morphine addiction and open up novel treatment options of these types of addiction (https://pubmed.ncbi.nlm.nih.gov/30384981/)
III- Understanding integrative molecular mechanisms involving especially FGFR1-5-HT1A heteroreceptor complexes and their receptor-receptor interactions. Also the 5-HT1A isoreceptor complexes and other 5-HT1A and oxytocin heteroreceptor complexes. This research may help us understand depression and provide novel, antidepressant drugs, especially of treatment resistant depression (https://pubmed.ncbi.nlm.nih.gov/26687454/)
IV- Understanding integrative molecular mechanisms involving especially A2AR-D2R heteroreceptor complexes and their receptor-receptor interactions in ventral striatum in relation to Schizophrenia. The role of distinc immune receptors and their potential physical interactions with NMDAR and D2R are also proposed to play a significant role in Schizophrenia. This research has led to the A2AR hypothesis of schizophrenia with A2AR-D2R complexes having a significant role. Targeting these complexes may lead to development of novel antipsychotic drugs (https://pubmed.ncbi.nlm.nih.gov/32349279/)
V- Understanding integrative molecular mechanisms involving especially A2AR-D2R heteroreceptor complexes and their receptor-receptor interactions in dorsal striatum is of high relevance to see what goes wrong in sensory-motor integration in Parkinson’s disease. This research has led to the hypothesis that disturbances in A2AR-D2R, A2AR-mGluR5 and A2AR-D2R-mGluR5 complexes have a significant role in Parkinsonn’s disease by enhancing the brake in motor activation. It is produced through overactivity in the dorsal striato-pallidal GABA pathway induced by inhibition of the inhibitory D2R function in the receptor complexes present in this pathway. Targeting these complexes may lead to development of novel antiparkinsonian drugs (https://pubmed.ncbi.nlm.nih.gov/30637481/)
The future looks highly interesting moving further into molecular integration and communication in health and disease and understanding the molecular basis of learning and memory.
Pedagogiska meriter
1968-1979 Prosektor – Histology, Karolinska Institutet, Sweden
1979-2005 Professor – Histology, Karolinska Institutet, Sweden
SUPERVISION OF GRADUATE STUDENTS AND POSTDOCTORAL FELLOWS
1971-2004 Main supervisor of 22 PhD Theses at Karolinska Institutet, Stockholm, Sweden
1971-2018 Supervisor of 43 post doctoral fellows at Karolinska Institutet, Stockholm, Sweden
POSITIONS OF TRUST
2017 Member of the Baillet Latour Scientific Committee for Medical Research. Belgium
2012 Ambassador for the 28th CINP World Congress Neuropsychopharmacology
2009 Chairman for independent awards committee for the outstanding contributions to the fields of basic and clinical acupuncture and meridian studies. South Korea
2008 Presentation of the IPSEN Award on Neuronal Plasticity at FENS, Geneva, Switzerland.
1986-2005 Member of the Nobel Assembly, Karolinska Institutet, Sweden
1980- Member of the Royal Swedish Academy of Sciences
1992-1995 Member of the Scientific Board and Kuratorium of the Max del Brück Center Germany
1983-1995 Member of the Medical Advisory Board of the American Parkinson Disease Association.
1993 Member of the Foundation IPSEN Jury on Neuronal Plasticity, Paris, France
Utbildning
1965-04-25 PhD, Histology, Karolinska Institutet, Sweden
1971 MD, Karolinska Institutet, Sweden
Akademiska priser och utmärkelser
ACADEMIC HONOURS
2019 Minisymposium (Fuxe, Svenningsson, Vukojevic and Borroto-Escuela) at the Nobel Forum, KI Neuroscience Networks. Sweden
2018 Chapter in 10th volume of "The History of Neuroscience by Autobiography”
2013 Foreign member of the Mexican Academy of Sciences, Mexico City, Mexico
2007 Doctor Honoris Cause, University of Malaga, Malaga, Spain
1986- 2005 Member of the Nobel Assembly, Stockholm, Sweden
1980- Member of the Royal Swedish Academy of Sciences
2005 Minisymposium on receptor-receptor interactions and volume transmission in honour of Kjell Fuxe at Karolinska Institutet. Sweden
2005 Lecture at the Melvin Yahr Memorial Symposium in the 16th International Congress on Parkinsons’s Disease and Related disorders in Berlin, Germany
2005 Honorary lecture at the Annual Italian Neuroscience Meeting in Ischia, Italy
2002 Doctor Honoris Cause, University of Ferrara, Ferrara, Italy
2000 Menek Goldstein Memorial Lecture, New York, USA
1999 Charles Medal, Prague, Czech
1998 Doctor Honoris Cause at the University of Barcelona, Spain
1993 Cass Memorial Lecture, University of Dundee, UK
1993 Honorary Doctorate at the Albert Einstein International Academy Foundation, USA
1992 Doctor Honoris Cause of Université Claude Bernard, Lyon, France
1992 The Albert Einstein International Academy Foundation Cross of Merit, USA
1991 The Albert Einstein Academy Foundation Alfred Nobel Medal for Peace, Kansas, USA
1990 The Albert Einstein Academy Bronze Medal Award, Missouri, USA
1988 Honorary Doctorate, Marquis Guiseppe Scicluna International University, USA
1980- Member of the Royal Swedish Academy of Science, Stockholm Sweden.
1977 Gold Medal for research on prolactin, First Int Prolactin Symposium, Nice, France
AWARDS AND PRIZES
2018 CINP pioneer award with receipt of Arvid Carlsson medal, June 16, Vienna, Austria
2018 Albert Nelson Marquis Lifetime Achievement Award by Marquis Who’s Who
2012 Camillo Golgi Medal Award, Golgi Foundation, Brescia, Italy
2012 “Sigillo d’Ateneo” University of Urbino, Italy
2009 Grant Award from Fundacio La Marato de TV3 ,Barcelona, Spain
2007 The university of Modena medal, Modena, Italy
2007 Rapid Response Innovation Award at the Michael J. Fox Foundation, USA
2006 The Palay Award in structural Neuroscience, Cajal Club, USA
2003 ECNP Neuropsychopharmacology Award 2003, by ECNP committee, Prague, Czech
1998 Humboldt Prize Award, Germany
1993 The Fishberg Professorship Award at the Mount Sinai Medical Center, USA
1992 IPSEN Prize by the IPSEN foundation, Paris, France
1990 The Adele and Robert Blank Lectureship Award, NYU Medical Center, USA
1985 The New York Academy of Sciences Award in Biological and Medical Sciences, USA
1980 International Madonina Prize of the Biological Sciences, Milan, Italy
1979 Hilda and Alfred Erikssons Prize of the Swedish Royal Academy, Sweden
1979 Erik H. Fernströms Reward at Karolinska Institute, Sweden
1975 Kaiser Award, Med Faculty, University of Honolulu, Hawaii, USA