The Role of PCSK9 in the Brain

2021.02.10 | Graduate School of Health

On Friday 26 February at 15:00, Angela Pärn defends her PhD dissertation entitled "The Role of PCSK9 in the Brain".

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein that is involved in the regulation of low-density lipoprotein (LDL) metabolism and plasma cholesterol levels. Its therapeutic inhibition efficiently lowers plasma cholesterol, and antibodies directed against PCSK9 are in clinical use. Furthermore, novel drugs that completely block PCSK9 synthesis have been recently approved. While PCSK9 is mostly expressed in the developing and adult liver, it is also present in several other tissues, including the brain. Intriguingly, PCSK9 expression in the brain peaks during cortical and cerebellar development and decreases markedly thereafter. Accordingly, PCSK9 has been proposed to have an important role in brain development and homeostasis. Thus, it is important to assure that the longterm inhibition of PCSK9 has no potential adverse neurological effects. The focus of this thesis was to study the consequences of altered PCSK9 activity in developing and adult mouse brain. The results demonstrate that although we find moderate changes in the brain lipids of PCSK9 KO mice, neither overexpression nor deficiency of PCSK9 during brain development nor low plasma cholesterol resulting from PCSK9 deficiency in adulthood has major consequences for brain functioning. Accordingly, our results complement the belief that the current and future PCSK9-inhibiting therapies are safe to use on patients.    

The summary is written by the PhD student.    

The defence is public and takes place online. Please read the attached press release for more information.

Contact:

PhD student Angela Pärn

Mail: angela.parn@biomed.au.dk

Phone: (+37) 256251645

Read full press release