Analysis of the Association between &lt;i&gt;Apolipoprotein D&lt;/i&gt; and Schizophrenia

Li, Dawei; Duan, Shiwei; Duan, Yun; Chen, Qingying; Li, Xingwang; Liu, Zhuangjun; Gao, Feng

doi:10.1159/000095740

Cited by 5 publications

(4 citation statements)

References 58 publications

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“…ApoD (Yoshida et al, 1996;Terrisse et al, 1998;Thomas et al, 2001Thomas et al, , 2003bOrdonez et al, 2006;Zhang et al, 2006). These data strongly reinforce the concept that there is true disease related connection between neurological diseases and ApoD.…”

Section: Discussionmentioning

confidence: 52%

Expression of somatostatin and somatostatin receptor subtypes in Apolipoprotein D (ApoD) knockout mouse brain: An immunohistochemical analysis

Rajput

Billová

Patel³

et al. 2009

Journal of Chemical Neuroanatomy

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Section: Discussionmentioning

confidence: 52%

Expression of somatostatin and somatostatin receptor subtypes in Apolipoprotein D (ApoD) knockout mouse brain: An immunohistochemical analysis

Rajput

Billová

Patel³

et al. 2009

Journal of Chemical Neuroanatomy

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“…Reference Collection 11 (Provost et al, 1995;Séguin et al, 1995;Namdar-Aligoodarzi et al, 2015;Lim et al, 2016;Diez-Hermano et al, 2020). Reference Collection 12 (Drayna et al, 1987;Eichner et al, 1989;Kamboh et al, 1989;Baker et al, 1994;Vijayaraghavan et al, 1994;Desai et al, 2002Desai et al, , 2003Helisalmi et al, 2004;Hansen et al, 2006;Zhang et al, 2006;Chen et al, 2008;Shibata et al, 2013;Lövkvist et al, 2014;Guven et al, 2019).…”

Section: Apod Systematic Review Reference Collectionsmentioning

confidence: 99%

The Lipocalin Apolipoprotein D Functional Portrait: A Systematic Review

Sánchez

Ganfornina

2021

Front. Physiol.

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Apolipoprotein D is a chordate gene early originated in the Lipocalin protein family. Among other features, regulation of its expression in a wide variety of disease conditions in humans, as apparently unrelated as neurodegeneration or breast cancer, have called for attention on this gene. Also, its presence in different tissues, from blood to brain, and different subcellular locations, from HDL lipoparticles to the interior of lysosomes or the surface of extracellular vesicles, poses an interesting challenge in deciphering its physiological function: Is ApoD a moonlighting protein, serving different roles in different cellular compartments, tissues, or organisms? Or does it have a unique biochemical mechanism of action that accounts for such apparently diverse roles in different physiological situations? To answer these questions, we have performed a systematic review of all primary publications where ApoD properties have been investigated in chordates. We conclude that ApoD ligand binding in the Lipocalin pocket, combined with an antioxidant activity performed at the rim of the pocket are properties sufficient to explain ApoD association with different lipid-based structures, where its physiological function is better described as lipid-management than by long-range lipid-transport. Controlling the redox state of these lipid structures in particular subcellular locations or extracellular structures, ApoD is able to modulate an enormous array of apparently diverse processes in the organism, both in health and disease. The new picture emerging from these data should help to put the physiological role of ApoD in new contexts and to inspire well-focused future research.

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“…Electrostatic repulsion might lead to subtle effects on the shape of the ligand pocket. Further genetic analyses describe single nucleotide polymorphisms that are linked to Alzheimer disease (46) or to schizophrenia (47,48), either via a mutation in the signal peptide or by influencing mRNA processing.…”

Section: Discussionmentioning

confidence: 99%

Structural Insight into the Dual Ligand Specificity and Mode of High Density Lipoprotein Association of Apolipoprotein D

Eichinger

Nasreen

Kim

et al. 2007

Journal of Biological Chemistry

137

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Human apolipoprotein D (ApoD) occurs in plasma associated with high density lipoprotein. Apart from the involvement in lipid metabolism, its binding activity for progesterone and arachidonic acid plays a role in cancer development and neurological diseases. The crystal structures of free ApoD and its complex with progesterone were determined at 1.8 Å resolution and reveal a lipocalin fold. The narrow, mainly uncharged pocket within the typical ␤-barrel accommodates progesterone with its acetyl side chain oriented toward the bottom. The cavity adopts essentially the same shape in the absence of progesterone and allows complexation of arachidonic acid as another cognate ligand. Three of the four extended loops at the open end of the ␤-barrel expose hydrophobic side chains, which is an unusual feature for lipocalins and probably effects association with the high density lipoprotein particle by mediating insertion into the lipid phase. This mechanism is in line with an unpaired Cys residue in the same surface region that can form a disulfide cross-link with apolipoprotein A-II.Human ApoD 2 (1, 2) is a glycoprotein of 169 amino acids, which was discovered in plasma (3) as an atypical lipoprotein. There, ApoD is peripherally associated with HDL via disulfide bond with ApoA-II (4), which itself forms an amphipathic ␣-helical belt that wraps around the lipid disc (5).ApoD was also isolated as a progesterone-binding protein abundant in mammary gross cystic disease fluid (6), and it was found as a monomeric protein in apocrine secretion, where it seems to bind odorants (7). ApoD mRNA is expressed in a variety of organs (8) as well as in certain human cancers. Indeed, ApoD has received attention as prognostic marker for various, often steroid-responsive tumors, including prostate cancer (9), breast carcinoma, and cutaneous malignant melanoma (10).In addition, ApoD is synthesized by astrocytes in the central nervous system (11), and there, it seems to be involved in arachidonic acid transport, metabolism, and signaling (12). Notably, ApoD plays a well documented pathophysiological role in several psychiatric disorders (12), especially in schizophrenia (13).ApoD has been prepared as a soluble recombinant protein via secretion into the periplasm of Escherichia coli, and its binding activity for progesterone and arachidonic acid, both with K D values around 1 M, was demonstrated (14). However, recombinant ApoD reveals a pronounced tendency to adsorb to surfaces and to form aggregates upon storage, which may be explained by hydrophobic surface properties that enable ApoD to interact with HDL and/or with lipid membranes in its physiological environment. Using systematic substitution of presumably exposed hydrophobic residues, we were able to construct a "solubilized" mutant of ApoD that retained native ligand binding function and appeared to be suitable for structural analysis (15). EXPERIMENTAL PROCEDURESProtein Production and Crystallization-An engineered version of ApoD was produced in E. coli via periplasmic secretion essent...

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Analysis of the Association between <i>Apolipoprotein D</i> and Schizophrenia

Cited by 5 publications

References 58 publications

Expression of somatostatin and somatostatin receptor subtypes in Apolipoprotein D (ApoD) knockout mouse brain: An immunohistochemical analysis

Expression of somatostatin and somatostatin receptor subtypes in Apolipoprotein D (ApoD) knockout mouse brain: An immunohistochemical analysis

The Lipocalin Apolipoprotein D Functional Portrait: A Systematic Review

Structural Insight into the Dual Ligand Specificity and Mode of High Density Lipoprotein Association of Apolipoprotein D

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