PCSK9 and the nervous system: a no-brainer?

Ali K Jaafar; Romuald Techer; Kévin Chemello; Gilles Lambert; Steeve Bourane

doi:10.1016/j.jlr.2023.100426

PCSK9 and the nervous system: a no-brainer?

J Lipid Res. 2023 Sep;64(9):100426. doi: 10.1016/j.jlr.2023.100426. Epub 2023 Aug 14.

Authors

Ali K Jaafar¹, Romuald Techer¹, Kévin Chemello¹, Gilles Lambert², Steeve Bourane¹

Affiliations

¹ Laboratoire Inserm UMR 1188 DéTROI, Saint-Pierre, La Réunion, France.
² Laboratoire Inserm UMR 1188 DéTROI, Saint-Pierre, La Réunion, France; Faculté de Médecine, Université de La Réunion, Saint-Pierre, La Réunion, France. Electronic address: gilles.lambert@univ-reunion.fr.

Abstract

In the past 20 years, PCSK9 has been shown to play a pivotal role in LDL cholesterol metabolism and cardiovascular health by inducing the lysosomal degradation of the LDL receptor. PCSK9 was discovered by the cloning of genes up-regulated after apoptosis induced by serum deprivation in primary cerebellar neurons, but despite its initial identification in the brain, the precise role of PCSK9 in the nervous system remains to be clearly established. The present article is a comprehensive review of studies published or in print before July 2023 that have investigated the expression pattern of PCSK9, its effects on lipid metabolism as well as its putative roles specifically in the central and peripheral nervous systems, with a special focus on cerebrovascular and neurodegenerative diseases.

Keywords: Alzheimer’s disease; Brain; LDL receptor; Nervous system; PCSK9; Stroke.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Brain / metabolism
Cholesterol, LDL
Nervous System*
Proprotein Convertase 9* / genetics
Proprotein Convertase 9* / metabolism
Receptors, LDL / genetics
Receptors, LDL / metabolism

Substances

PCSK9 protein, human
Proprotein Convertase 9
Cholesterol, LDL
Receptors, LDL