Apolipoprotein D

Abstract

Apolipoprotein D (apoD) is a 29-kDa glycoprotein that is primarily associated with high density lipoproteins in human plasma. It is an atypical apolipoprotein and, based on its primary structure, apoD is predicted to be a member of the lipocalin family. Lipocalins adopt a beta-barrel tertiary structure and transport small hydrophobic ligands. Although apoD can bind cholesterol, progesterone, pregnenolone, bilirubin and arachidonic acid, it is unclear if any, or all of these, represent its physiological ligands. The apoD gene is expressed in many tissues, with high levels of expression in spleen, testes and brain. ApoD is present at high concentrations in the cyst fluid of women with gross cystic disease of the breast, a condition associated with increased risk of breast cancer. It also accumulates at sites of regenerating peripheral nerves and in the cerebrospinal fluid of patients with neurodegenerative conditions, such as Alzheimer's disease. ApoD may, therefore, participate in maintenance and repair within the central and peripheral nervous systems. While its role in metabolism has yet to be defined, apoD is likely to be a multi-ligand, multi-functional transporter. It could transport a ligand from one cell to another within an organ, scavenge a ligand within an organ for transport to the blood or could transport a ligand from the circulation to specific cells within a tissue.

Schizophrenia Breakdown in the Well-regulated Lifelong Process of Brain Development and Maturation

“…Apolipoprotein D levels have been shown to be elevated in old age and in a number of other neuropathologic disorders such as Alzheimer's disease (Kalman et al 2000) and excitotoxic damage (Montpied et al 1999) in regionally specific patterns. This suggests that upregulation of apolipoprotein D may be a localized response to regional brain lipid pathology (for review see Rassart et al 2000). This possibility is supported by the observation that in an animal model of Niemann-Pick disease (degenerative disease involving cholesterol homeostasis) most of the apolipoprotein D was associated with the myelin fraction (Suresh et al 1998).…”

A neuroscientist's guide to lipidomics

“…We do not know precisely how 2-AG crosses the water-filled cleft to reach CB 1 r-containing terminals, but its amphipathic nature and/or its association with extracellular lipid-binding proteins 69,70 are likely to be important. Another element that may facilitate the transynaptic movement of 2-AG relates to the molecular structure of the CB 1 r. CB 1 r belongs to a subgroup of about 60 G-protein-coupled receptors that contain a characteristic alkyl-binding domain that is implicated in the recognition of lipid ligands 71 .…”

Apolipoprotein D is Elevated in Oligodendrocytes in the Peri-Infarct Region after Experimental Stroke: Influence of Enriched Environment

“…Studies in Drosophila show that deletion of a homolog of apoD, GLaz reduces lifespan and stress resistance, whereas overexpression has the opposite effects (Sanchez et al, 2006;Walker et al, 2006), suggesting a protective role of apoD. Along the same line is the finding that apoD binds toxic arachidonic acid and heme-related products (Rassart et al, 2000). In addition, apoD could be an important source of cholesterol and lipid reutilization in regenerative processes by sequestering these components released by the dying neurons.…”

“…In the CNS, apoD expression is mainly localized to oligodendrocytes and neuronal populations (Ong et al, 1997;Rassart et al, 2000). Apolipoprotein D mRNA is elevated at sites of regenerating peripheral nerves (Boyles et al, 1990;Spreyer et al, 1990), and CNS injury increases expression of apoD mRNA and protein levels (Franz et al, 1999).…”