Potential Roles of Peroxisomes in Alzheimer's Disease and in Dementia of the Alzheimer's Type

Article type: Review Article

Authors: Lizard, Gérard^{a; *} | Rouaud, Olivier^b | Demarquoy, Jean^a | Cherkaoui-Malki, Mustapha^a | Iuliano, Luigi^{c; *}

Affiliations: [a] Centre de Recherche INSERM 866 ‘Lipides, Nutrition, Cancer’, Université de Bourgogne Equipe ‘Biochimie du peroxysome, Inflammation et Métabolisme Lipidique’, Dijon, France | [b] Service de Neurologie, CHU de Dijon, Dijon, France | [c] Department of Medico-Surgiacl Sciences and Biotechnology, Laboratory of Vascular Biology and Mass Spectrometry, Sapienza University of Rome, Latina, Italy

Correspondence: [*] Correspondence to: Dr. Gérard Lizard, Ph.D., Centre de Recherche INSERM 866 – Equipe BIO-peroxIL, Faculté des Sciences Gabriel, 6 Bd Gabriel, 21000 Dijon, France. Tel.: +33 380 39 62 56; Fax: +33 380 39 62 50; E-mail: [email protected] and Prof. Luigi Iuliano, MD, Department of MedicaSurgical Sciences and Biotechnology, Laboratory of Vascular Biology and Mass Spectrometry, Sapienza University of Rome, corso della Republica 79, 04100 Latina, Italy. Tel.: +39 0773 31757231; Fax: +39 06 62 29 1089; E-mail: [email protected].

Abstract: In Alzheimer's disease (AD) and dementia of the Alzheimer's type (DAT), the role played by peroxisomes is not well known. Peroxisomes are present in all eukaryotic cells, with the exception of erythrocytes. They are involved in the β-oxidation process of long-chain fatty acids, very-long-chain fatty acids, and branched-chain fatty acids. They participate in the α-oxidation of phytanic acid, the biosynthesis of bile acids, and the breakdown of eicosanoids. Peroxisomes are also involved in the synthesis of specific fatty acids such as docosahexaenoic acid (DHA), which is essential for the brain and retina, and plasmalogens (PLGN), which play crucial roles in neural cells and are essential components of myelin. Several studies conducted in animal models and in humans provided evidence for a role of DHA in preventing brain degeneration. Significantly lower levels of PLGN were observed in patients with severe dementia. Moreover, a decreased activity of carnitine acetyltransferase, an enzyme present in peroxisome (but also detected in mitochondria, endoplasmic reticulum, and nucleus), was reported in AD patients. We give an overview of the potential role of peroxisomes, especially in the part played by DHA, PLGN, carnitine, and carnitine-dependent peroxisomal enzymes, on the development of AD and DAT. The potential of developing novel therapies targeted on peroxisomal metabolism to prevent cognitive decline and other age-related neurological disorders is discussed.

Keywords: Alzheimer's disease, carnitine-dependent enzymes, dementia, DHA, peroxisome, plasmalogen

DOI: 10.3233/JAD-2011-111163

Journal: Journal of Alzheimer's Disease, vol. 29, no. 2, pp. 241-254, 2012