Role of HIF-P4H inhibition and HIF stabilisation in inflammatory diseases

Thesis event information

Date and time of the thesis defence

Place of the thesis defence

Leena Palotie Auditorium (101A), Kontinkangas Campus (Aapistie 5). Remote access: https://oulu.zoom.us/j/69194989535?pwd=Smw1VjVYKzZwMjl5MVR4Y3piQmZPZz09

Topic of the dissertation

Role of HIF-P4H inhibition and HIF stabilisation in inflammatory diseases

Doctoral candidate

Licentiate of medicine Teemu Ollonen

Faculty and unit

University of Oulu Graduate School, Faculty of Biochemistry and Molecular Medicine, ECM and Hypoxia

Subject of study

Biochemistry and molecule medicine

Opponent

Professor Mikko Hiltunen, University of Eastern Finland

Custos

Professor Peppi Karppinen, University of Oulu

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The hypoxia response provides protection against central nervous system degenerative diseases

Hypoxia-inducible factor (HIF) is a vital molecule that regulates the body’s hypoxia response, aiming to ensure optimal tissue oxygen uptake and energy metabolism in a state in which oxygen is not available in sufficient amounts at tissue level. HIF stabilization is regulated by 3 distinct HIF-prolyl 4-hydroxylase enzymes, whose action by either physiological oxygen depletion or drug inhibition elicits the activation of a hypoxic response and an immediate response to its regulatory pathways. For these regulatory pathways, there are several indications, in addition to the effects on basal metabolism and circulation, of the responses that regulate chronic inflammation.

The dissertation study examined the effect of these regulatory pathways on inflammatory diseases both in terms of general metabolism and in particular in terms of chronic inflammatory degenerative diseases of the central nervous system. The dissertation investigated the course of chronic inflammatory diseases modeled using different mouse lines and research settings, and tested the curative effects of the hypoxia response elicited by different methods.

The results show that activation of the chronic hypoxia response reduces overall obesity in mice, protects against alcohol-induced hepatic steatosis, and provides protection against amyloidogenic accumulation and degenerative diseases of the central nervous system and inflammatory demyelinating diseases. The results of the study provide new information on the course of the disease for these diseases, as well as indications of the therapeutic potential of new drugs to protect against the disease.
Last updated: 19.3.2021