Kjell Fuxe, Professor Emeritus, portrait format

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

Kjell Fuxe

Affiliated to research

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

Department and organisational affiliation:

About me

I have been working on understanding the communication and integration of neuronal-glial networks of the brain. This research provided evidence for the existence of central monoamine neurons, volume transmission and its different forms, and receptor-receptor interactions in heteroreceptor complexes in the CNS. I applied this knowledge to develop novel strategies for treatment of Schizophrenia, depression, cocaine addiction and Parkinson's disease.

This research introduced for example, several dopamine receptor agonists for treatment of Parkinson's disease and lead to important work in molecular neuropsychopharmacology. Integration of synaptic and volume transmission signals can take place through synaptic and extrasynaptic heteroreceptor complexes, becoming a new major mechanism for neuromodulation of synapses. The reorganization of homo- and heteroreceptor complexes in the postsynaptic membrane with novel adaptor proteins may form the molecular basis for learning and memory. The novel heteroreceptor complexes discovered represents new targets for treatment of mental and neurological diseases. 

Research description

The concept of allosteric receptor-receptor interactions in G protein-coupled receptor (GPCR) homo- and heteroreceptor complexes, in which they physically interact, provides a new dimension to molecular integration in the brain. The receptor-receptor interactions dynamically change recognition, pharmacology, signaling and trafficking of the participating receptors and thus their function. We introduced a novel hypothesis that vulnerability of distinct GPCR heteroreceptor complexes can be a major cause for brain disorders involving dramatic dysfunction through marked changes in their densities and allosteric receptor-receptor interactions.

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. 

Teaching portfolio

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

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

 

Education

1965-04-25      PhD, Histology, Karolinska Institutet, Sweden

1971                MD, Karolinska Institutet, Sweden

Academic honours, awards and prizes

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

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, 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

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

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