Hypoxia response in neurological diseases. The role of HIF-P4H inhibition in Alzheimer’s disease and PHYH deficiency in Refsum disease
Thesis event information
Date and time of the thesis defence
Place of the thesis defence
Lecture hall F101, Aapistie 7, Oulu
Topic of the dissertation
Hypoxia response in neurological diseases. The role of HIF-P4H inhibition in Alzheimer’s disease and PHYH deficiency in Refsum disease
Doctoral candidate
Master of Science Margareta Kurkela
Faculty and unit
University of Oulu Graduate School, Faculty of Biochemistry and Molecular Medicine, ECM & Hypoxia
Subject of study
Biochemistry and Molecular Medicine
Opponent
Associate Professor Blanca I. Aldana, University of Copenhagen
Custos
Professor Peppi Karppinen, University of Oulu
Effects of sensing hypoxia in Alzheimer's disease and Refsum disease
Activation of hypoxia response protects neurons in a mouse model for Alzheimer’s disease. Hypoxia refers to decreased oxygen availability. Hypoxia inducible factor (HIF) senses hypoxia, and in a low oxygen environment HIF induces the expression of hundreds of genes which are involved with for example energy metabolism and development of blood vessels. Moderate hypoxia has been discovered to be beneficial for health.
In this PhD thesis, the effects of moderate hypoxia and activation of hypoxia response in a mouse model of Alzheimer’s disease were investigated. It was discovered that hypoxia reduces accumulation of the β-amyloid and improves the survival of neural cells in the mouse model. Additionally for these effects, inducing HIF in normal room air protects the mice from behavioral changes detected in Alzheimer’s disease.
Refsum disease is an accumulation disorder where phytanic acid, mainly acquired from milk products, accumulates in the body leading to neurological symptoms, such as weakening of peripheral nerves and issues with voluntary movements.
In this PhD thesis, phytanoyl-CoA dioxygenase (PHYH) was investigated. Mutations in PHYH cause Refsum disease. It was discovered that PHYH is an oxygen sensing enzyme expressed in a wide variety of tissues. These results increase understanding of the Refsum disease.
In this PhD thesis, the effects of moderate hypoxia and activation of hypoxia response in a mouse model of Alzheimer’s disease were investigated. It was discovered that hypoxia reduces accumulation of the β-amyloid and improves the survival of neural cells in the mouse model. Additionally for these effects, inducing HIF in normal room air protects the mice from behavioral changes detected in Alzheimer’s disease.
Refsum disease is an accumulation disorder where phytanic acid, mainly acquired from milk products, accumulates in the body leading to neurological symptoms, such as weakening of peripheral nerves and issues with voluntary movements.
In this PhD thesis, phytanoyl-CoA dioxygenase (PHYH) was investigated. Mutations in PHYH cause Refsum disease. It was discovered that PHYH is an oxygen sensing enzyme expressed in a wide variety of tissues. These results increase understanding of the Refsum disease.
Last updated: 13.5.2024