The DOI matches its Crossref record; 87 of the 88 references it cites were found in a registry or an index.
Apolipoprotein E structure: insights into function
Abstract
Human apolipoprotein E (apoE) is a member of the family of soluble apolipoproteins. Through its interaction with members of the low-density lipoprotein receptor family, apoE has a key role in lipid transport both in the plasma and in the central nervous system. Its three common structural isoforms differentially affect the risk of developing atherosclerosis and neurodegenerative disorders, including Alzheimer's disease. Because the function of apoE is dictated by its structure, understanding the structural properties of apoE and its isoforms is required both to determine its role in disease and for the development of therapeutic strategies.
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In the citing paper
“Several biophysical studies have shown that apoE displays low thermodynamic stability and significant conformational plasticity, and allelic differences as well as single point mutations have been shown to affect protein conformation and to hinder physiological function”
From Thermodynamic destabilization and aggregation propensity as the mechanism behind the association of apoE3 mutants and lipoprotein glomerulopathy (2018) · cites this paper as [13]
In the citing paper
“Several biophysical studies have shown that apoE displays low thermodynamic stability and significant conformational plasticity, and allelic differences as well as single point mutations have been shown to affect protein conformation and to hinder physiological function”
From Thermodynamic destabilization and aggregation propensity as the mechanism behind the association of apoE3 mutants and lipoprotein glomerulopathy (2018) · cites this paper as [13]
In the citing paper
“Inter-domain interactions within apoE have been hypothesized to underlie key conformational changes related to apoE function [44], [45].”
From Biophysical Analysis of Apolipoprotein E3 Variants Linked with Development of Type III Hyperlipoproteinemia (2011) · cites this paper as [44]
In the citing paper
“Several studies have suggested that the structural and biophysical properties of apoE can dictate the function of the protein and have provided insight into the mechanisms by which apoE is involved in cardiovascular and neurological diseases [42], [43], [44], [45], [46], [47], [48], [49].”
From Biophysical Analysis of Apolipoprotein E3 Variants Linked with Development of Type III Hyperlipoproteinemia (2011) · cites this paper as [44]
In the citing paper
“of the second unfolding transition of apoE3 variant (Table 3) that corresponds to the unfolding of the N-terminal domain where the K146E mutation is located [13], [44], [65].”
From Biophysical Analysis of Apolipoprotein E3 Variants Linked with Development of Type III Hyperlipoproteinemia (2011) · cites this paper as [44]
In the citing paper
“Apo E4 isoform is associated with elevated total and LDL-cholesterol levels, due to the higher affinity of apo E4 for VLDL and LDL”
From Description of a Large Family with Autosomal Dominant Hypercholesterolemia Associated with the APOE p.Leu167del Mutation (2013) · cites this paper as Hatters DM et al. 2006
In the citing paper
“Mutated ApoE2 (Arg158Cys) exhibits only 2% affinity to LDL receptor compared to the wide type ApoE3 isoform [13]”
From A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation (2024) · cites this paper as [13]
In the citing paper
“Biophysical and computational analyses suggest that unfolding of the N-terminal domain constitutes a necessary conformational change for lipid binding and apoE function (19).”
From Molecular Basis for Increased Risk for Late-onset Alzheimer Disease Due to the Naturally Occurring L28P Mutation in Apolipoprotein E4 (2014) · cites this paper as [19]
In the citing paper
“ApoE variants with lower thermodynamic stability and changes in conformational plasticity have been shown to have altered interdomain interactions and defective physiological functions (19, 24 -28).”
From Molecular Basis for Increased Risk for Late-onset Alzheimer Disease Due to the Naturally Occurring L28P Mutation in Apolipoprotein E4 (2014) · cites this paper as [19]
In the citing paper
“First, apoE4 preferentially forms a “molten globule state” that ultimately reduces the in vitro stability of apoE4 relative to the other isoforms.”
From Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels (2008) · cites this paper as Hatters et al., 2006
In the citing paper
“Second, apoE4 forms a unique salt bridge interaction between Arg-61 in the N terminal and Glu-255 in the carboxy-terminal domain.”
From Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels (2008) · cites this paper as Hatters et al., 2006
In the citing paper
“ApoE contains two independently folded functional domains; these are a 22-kDa N-terminal domain (residues 1–191) and a 10-kDa C-terminal domain (residues 216–299) linked by a hinge region (18, 19).”
From Role of the N- and C-Terminal Domains in Binding of Apolipoprotein E Isoforms to Heparan Sulfate and Dermatan Sulfate: A Surface Plasmon Resonance Study (2008) · cites this paper as [19]
In the citing paper
“This domain interaction mediated by a salt bridge formation between Arg-61 and Glu-255 is unique to apoE4 (Fig. 1) [15].”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [15]
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Lipid Droplets and Cellular Lipid Metabolism
Walther, T. C., & Farese, R. V. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061009-102430 · Cited by 1,701
“Apo E binds lipoproteins by opening its four-helix bundle and exposing hydrophobic, amphipathic sequences to the lipid surface (86).”
BackgroundApolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C.-C., & Bu, G. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0228-7 · Cited by 1,425
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“Human APOE contains 299 amino acid residues and has independently folded amino-terminal and carboxy-terminal domains, which are joined together by a flexible hinge regio”
BackgroundMolecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994
“ε2 encodes Cys residues at the position 112 and 158, ε3 encodes a Cys residue at position 112 and a Arg residue at position 158, and ε4 comprises Arg residues at both positions [447].”
BackgroundBrasaemle, D. (2007) · Journal of Lipid Research · doi:10.1194/jlr.r700014-jlr200 · Cited by 997
“helices into the acyl chains of the surface phospholipid monolayer of lipoproteins (34, 35).”
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Verghese, P. B., Castellano, J. M., & Holtzman, D. M. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70325-2 · Cited by 857
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“The precise mechanisms by which ε2 carriage (and, hence, apo E2 isoforms) might confer advantageous lipid profiles (or other possible cardioprotective effects) are only partially understood.(167) They may relate to comparatively more efficient binding of apo E2 isoforms with Figure 4.”
ApoE and Aβ in Alzheimer’s Disease: Accidental Encounters or Partners?
Kanekiyo, T., Xu, H., & Bu, G. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.045 · Cited by 608
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APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes
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“Given the reported impairment of APOE4’s lipid-transport function 22 , and our finding of associations with lipid metabolism (Fig.”
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“Impaired PC biosynthesis might influence apo E association with VLDLs directly since the phospholipid species that bind to apo E can dramatically change the protein conformation and potentially alter the biological activity of apo E [80].”
BackgroundPencheva, N., Tran, H., Buss, C., Huh, D., Drobnjak, M., Busam, K., & Tavazoie, S. F. (2012) · Cell · doi:10.1016/j.cell.2012.10.028 · Cited by 415
“The three isoforms differ at residues 112 and 158 in the N-terminal region, which contains the receptor-binding domain (Hatters et al., 2006).”
Apolipoprotein E in Alzheimer's Disease: An Update
Yu, J.-T., Tan, L., & Hardy, J. (2014) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071013-014300 · Cited by 394
APOE and Alzheimer’s Disease: From Lipid Transport to Physiopathology and Therapeutics
Husain, M. A., Laurent, B., & Plourde, M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.630502 · Cited by 353
Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels
Riddell, D. R., Zhou, H., Atchison, K., Warwick, H. K., Atkinson, P. J., Jefferson, J., Xu, L., Aschmies, S., Kirksey, Y., Hu, Y., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1972-08.2008 · Cited by 346
“ApoE4 has two major structural characteristics that distinguish it from apoE3 or apoE2 (Hatters et al., 2006).”
BackgroundSharma, P., Srivastava, P., Seth, A., Tripathi, P. N., Banerjee, A. G., & Shrivastava, S. K. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.12.006 · Cited by 331
Apolipoprotein E isoforms and lipoprotein metabolism
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“The latter interaction occurs in quasi-spherical apoE/dipalmitoyl phosphatidylcholine particles where the two apoE molecules adopt a horseshoe shape (7,26).”
BackgroundImpact of apoE genotype on oxidative stress, inflammation and disease risk
Jofre‐Monseny, L., Minihane, A. M., & Rimbach, G. H. (2008) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200700322 · Cited by 326
“This is thought to impact on the chemical and thermal stability of the protein and in the formation of folding intermediates, with apoE2 showing the greatest stability and least formation of intermediates, while apoE4 shows the opposite properties, forming a typical molten globule configuration [20].”
ApoE Cascade Hypothesis in the pathogenesis of Alzheimer’s disease and related dementias
Martens, Y. A., Zhao, N., Liu, C.-C., Kanekiyo, T., Yang, A. J., Goate, A. M., Holtzman, D. M., & Bu, G. (2022) · Neuron · doi:10.1016/j.neuron.2022.03.004 · Cited by 316
Apolipoprotein E, Especially Apolipoprotein E4, Increases the Oligomerization of Amyloid β Peptide
Hashimoto, T., Serrano-Pozo, A., Hori, Y., Adams, K. W., Takeda, S., Banerji, A. O., Mitani, A., Joyner, D., Thyssen, D. H., Bacskai, B. J., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.1542-12.2012 · Cited by 294
“The C-terminal domain of apoE contains the major lipidbinding region (243–272 aa residues; Hatters et al., 2006; Mahley et al., 2009).”
BackgroundApolipoprotein E: Structural Insights and Links to Alzheimer Disease Pathogenesis
Chen, Y., Strickland, M. R., Soranno, A., & Holtzman, D. M. (2021) · Neuron · doi:10.1016/j.neuron.2020.10.008 · Cited by 298
“As discussed, only two structural models of lipidated recombinant ApoE have been assessed (Hatters et al., 2006; Henry et al., 2018).”
Apolipoprotein E: From lipid transport to neurobiology
Hauser, P. S., Narayanaswami, V., & Ryan, R. O. (2011) · Progress in Lipid Research · doi:10.1016/j.plipres.2010.09.001 · Cited by 320
“Finally, other studies point to a role of apoE4 in potentiating Ab-induced lysosomal leakage [152,198] and/or activating the endoplasmic reticulum stress response, leading to increased apoptosis [199,200].”
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“ApoE in human populations exhibits E2, E3, and E4 isoforms, of which E3 is the most common (Hatters et al., 2006).”
Pyrene: A Probe to Study Protein Conformation and Conformational Changes
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Structure of HDL: Particle Subclasses and Molecular Components
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“The three human APOE isoforms differ from one another in the protein sequence at amino acid positions 112 and 158 (Figure 1; Mahley, 1988; Raffai et al., 2001; Hatters et al., 2006).”
BackgroundTIP47 functions in the biogenesis of lipid droplets
Bulankina, A. V., Deggerich, A., Wenzel, D., Mutenda, K. E., Wittmann, J., Rudolph, M. G., Burger, K. N. J., & Höning, S. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200812042 · Cited by 268
“ApoE is also a major determinant of lipoprotein particle recognition and uptake via the low density lipoprotein receptor and other related receptors (Hatters et al., 2006).”
Cholesterol: its regulation and role in central nervous system disorders
Orth, M., & Bellosta, S. (2012) · Cholesterol · doi:10.1155/2012/292598 · Cited by 339
“Therefore, irrespective of the amino acid at position 112, animal apoE behaves like human apoE3 [192].”
BackgroundHigh Density Lipoprotein Structure–Function and Role in Reverse Cholesterol Transport
Lund-Katz, S., & Phillips, M. C. (2010) · Subcellular Biochemistry · doi:10.1007/978-90-481-8622-8_7 · Cited by 262
“…with studies of other natural apoE mutations have led to the identification of a cluster of basic amino acids in the regions spanning residues 136–150 as the recognition site responsible for the binding of apoE to the low density lipoprotein (LDL) receptor (Hatters et al., 2006; Weisgraber, 1994).”
BackgroundInfluentialWagner, S., Zensi, A., Wien, S., Tschickardt, S., Maier, W., Vogel, T., Worek, F., Pietrzik, C. U., Kreuter, J., & von Briesen, H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032568 · Cited by 265
Nanoparticles for Targeted Brain Drug Delivery: What Do We Know?
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“Apolipoprotein E (ApoE) is a family member of soluble apolipoproteins [91,92].”
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Thoe, E. S., Fauzi, A., Tang, Y.-Q., Chamyuang, S., & Chia, A. Y. Y. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119129 · Cited by 234
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APOε4 is associated with enhanced in vivo innate immune responses in human subjects
Gale, S. C., Gao, L., Mikacenic, C., Coyle, S. M., Rafaels, N., Murray Dudenkov, T., Madenspacher, J. H., Draper, D. W., Ge, W., Aloor, J. J., et al. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.01.032 · Cited by 202
“Compared with the common (wildtype) ApoE3 variant, which is found mostly in high-density lipoprotein particles, ApoE4 has increased N-C–terminal interactions that favor its association with VLDL(7) and decreased stability.(8) In addition to associations with cardiovascular disease and Alzheimer disease,(6) ApoE4 has m…”
Bains, G. K., Kim, S. H., Sorin, E. J., & Narayanaswami, V. (2012) · Biochemistry · doi:10.1021/bi3005285 · Cited by 209
Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease
Najm, R., Jones, E. A., & Huang, Y. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0324-6 · Cited by 183
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Lipid droplet proteins and metabolic diseases
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“How the allele-specific effects on antioxidant activity relate to the intrinsic differences in protein structure is yet to be determined, but it may have to do with the differential cysteine content of the three isoforms at residue 112 (outlined in Section 2) since cysteine itself binds metal ions (Hatters et al., 200…”
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Brasaemle, D., Subramanian, V., Garcia, A., Marcinkiewicz, A., & Rothenberg, A. (2008) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-008-9998-8 · Cited by 182
“Although the 4-helix bundle assumes a closed conformation when apolipoprotein E is soluble, it opens up to embed the hydrophobic faces of the 4 helices into the acyl chains of phospholipid monolayers covering lipoproteins [33, 34].”
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Moulton, M. J., Barish, S., Ralhan, I., Chang, J., Goodman, L. D., Harland, J. G., Marcogliese, P. C., Johansson, J. O., Ioannou, M. S., & Bellen, H. J. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2112095118 · Cited by 180
Saeed, A., Feofanova, E. V., Yu, B., Sun, W., Virani, S. S., Nambi, V., Coresh, J., Guild, C., Boerwinkle, E., Ballantyne, C. M., et al. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.04.050 · Cited by 176
“The different relationships of RLP-C and LDL-TG with APOE ε2/2 may be explained in part by the low affinity of apoE2 for the LDL (apoB/E) receptor, potentially leading to delayed clearance of VLDL and chylomicron remnants (48).”
Hultman, K., Strickland, S., & Norris, E. H. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.76 · Cited by 183
Hepatitis C Virus Attachment Mediated by Apolipoprotein E Binding to Cell Surface Heparan Sulfate
Jiang, J., Cun, W., Wu, X., Shi, Q., Tang, H., & Luo, G. G. (2012) · Journal of Virology · doi:10.1128/jvi.07222-11 · Cited by 190
“ApoE is a 34-kDa (299 amino acids) apoprotein containing a 22-kDa N-terminal domain (residues 1 to 191) that is recognized by the receptor(s) and a 10-kDa C-terminal domain (residues 222 to 299) that interacts with phospholipids (31, 35, 51).”
BackgroundMartínez-Morillo, E., Hansson, O., Atagi, Y., Bu, G., Minthon, L., Diamandis, E. P., & Nielsen, H. M. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1266-2 · Cited by 168
“The Apoe2 and Apoe4 isoforms differ in only one amino acid as compared to Apoe3, but this substitution affects their structure and function [12].”
BackgroundApolipoprotein E and cholesterol in aging and disease in the brain
de Chaves, E. P., Narayanaswami, V., Christoffersen, C., & Nielsen, L. B. (2008) · Future Lipidology · doi:10.2217/17460875.3.5.505 · Cited by 164
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“with very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) in plasma [21, 26, 28, 29].”
BackgroundHu, J., Liu, C.-C., Chen, X.-F., Zhang, Y.-W., Xu, H., & Bu, G. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0001-3 · Cited by 161
“Previous studies have shown that apoE2 may exhibit a more stable conformation [40] and”
BackgroundUnderstanding the association of apolipoprotein E4 with Alzheimer disease: clues from its structure
Zhong, N., & Weisgraber, K. H. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.r800009200 · Cited by 159
Self-citationDirect Transcriptional Effects of Apolipoprotein E
Theendakara, V., Peters-Libeu, C. A., Spilman, P., Poksay, K. S., Bredesen, D. E., & Rao, R. V. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.3562-15.2016 · Cited by 152
“Although it is true that ApoE3 and ApoE4 are known to change structures depending on how much lipid is associated with the protein (Hatters et al., 2006; Peters-Libeu et al., 2006), it is likely that several different conformations of both ApoE3 and ApoE4 were present in our system.”
BackgroundSelf-citationOxidative Stress and Metabolic Syndrome: Cause or Consequence of Alzheimer's Disease?
Contreras, D. L., Carvajal, K., Toral-Ríos, D., Franco-Bocanegra, D., & Campos‐Peña, V. (2014) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2014/497802 · Cited by 155
“(Arg, Arg) [35].”
Garai, K., Verghese, P. B., Baban, B., Holtzman, D. M., & Frieden, C. (2014) · Biochemistry · doi:10.1021/bi5008172 · Cited by 145
APOE genotype and stress response - a mini review
Dose, J., Huebbe, P., Nebel, A., & Rimbach, G. (2016) · Lipids in Health and Disease · doi:10.1186/s12944-016-0288-2 · Cited by 137
“Basis of the APOE protein isoforms are single amino acid interchanges at positions 112 and 158 (APOE3 has cysteine on residue 112 and arginine at residue 158, while APOE2 carries cysteine and APOE4 arginine on both positions; [38, 39]).”
BackgroundFrieden, C., Wang, H., & Ho, C. M. W. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705080114 · Cited by 134
“with an earlier prediction that had proposed only a single salt bridge between the two domains of apoE4 and no such interactions in apoE3 (9).”
BackgroundInfluentialFrieden, C., & Garai, K. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207022109 · Cited by 133
“The isolated C-terminal domain is known to aggregate (9), thereby preventing structure determination by standard methods.”
BackgroundResultInfluentialMarduel, M., Ouguerram, K., Serre, V., Bonnefont-Rousselot, D., Marques-Pinheiro, A., Erik Berge, K., Devillers, M., Luc, G., Lecerf, J.-M., Tosolini, L., et al. (2013) · Human Mutation · doi:10.1002/humu.22215 · Cited by 133
“Apo E distribution in each lipoprotein fraction showed a higher proportion in HDLs (77% vs. 63%– 69”
BackgroundInfluentialMaffre, P., Nienhaus, K., Amin, F., Parak, W. J., & Nienhaus, G. U. (2011) · Beilstein Journal of Nanotechnology · doi:10.3762/bjnano.2.43 · Cited by 133
Fitz, N. F., Nam, K. N., Wolfe, C. M., Letronne, F., Playso, B. E., Iordanova, B. E., Kozai, T. D. Y., Biedrzycki, R. J., Kagan, V. E., Tyurina, Y. Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23762-0 · Cited by 129
Cun, W., Jiang, J., & Luo, G. G. (2010) · Journal of Virology · doi:10.1128/jvi.01021-10 · Cited by 127
“Studies with lipid-free apoE proteins suggested that there are interactions between the N- and C-terminal domains only in apoE4, not in apoE2 or apoE3 (19, 21).”
BackgroundBlood protein coating of gold nanoparticles as potential tool for organ targeting
Schäffler, M., Sousa, F., Wenk, A., Sitia, L., Hirn, S., Schleh, C., Haberl, N., Violatto, M. B., Canovi, M., Andreozzi, P., et al. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2013.12.100 · Cited by 128
“So, it is smaller than HSA and has an elongated structure in a lipid-free state [36].”
BackgroundLee, J., Acosta, E. G., Stoeck, I. K., Long, G., Hiet, M., Mueller, B., Fackler, O., Kallis, S., & Bartenschlager, R. F. W. (2014) · Journal of Virology · doi:10.1128/jvi.01660-14 · Cited by 126
“We note that ApoE is able to interact with phospholipid head groups and is known to undergo large conformational changes in the presence of lipids (16).”
BackgroundInfluentialApoE genotype, cardiovascular risk and responsiveness to dietary fat manipulation
Minihane, A. M., Jofre‐Monseny, L., Olano-Martin, E., & Rimbach, G. H. (2007) · Proceedings of The Nutrition Society · doi:10.1017/s0029665107005435 · Cited by 128
“The Cys112 to Arg112 substitution in apoE4, although not appearing to appreciably influence receptor binding, is thought to impact on both protein stability and carboxyl-terminal and amino-terminal domain interactions (for review, see Hatters et al .”
InfluentialTLR4 Targeting as a Promising Therapeutic Strategy for Alzheimer Disease Treatment
Zhou, Y., Chen, Y., Xu, C., Zhang, H., & Lin, C. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.602508 · Cited by 120
Zensi, A., Begley, D. J., Pontikis, C., Legros, C., Mihoreanu, L., Büchel, C., & Kreuter, J. (2010) · Journal of drug targeting · doi:10.3109/1061186x.2010.513712 · Cited by 119
“Whereas apolipoprotein E appears to preferentially interact with receptors of the low-density lipoprotein (LDL) receptor family (Hatters et al., 2006), Apo A-I seems to prefer the scavenger receptors, important receptors of the macrophage system.”
BackgroundA rapid and cost-effective method for genotyping apolipoprotein E gene polymorphism
Zhong, L., Xie, Y.-Z., Cao, T.-T., Wang, Z., Wang, T., Li, X., Shen, R.-C., Xu, H., Bu, G., & Chen, X. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0069-4 · Cited by 113
“binding; therefore apoE modulates cholesterol homeostasis in an isoform-dependent manner [13].”
BackgroundAPOE3 -Jacksonville (V236E) variant reduces self-aggregation and risk of dementia
Liu, C.-C., Murray, M. E., Li, X., Zhao, N., Wang, N., Heckman, M. G., Shue, F., Martens, Y., Li, Y., Raulin, A.-C., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abc9375 · Cited by 108
Zhao, L., Gottesdiener, A. J., Parmar, M., Li, M., Kaminsky, S. M., Chiuchiolo, M. J., Sondhi, D., Sullivan, P. M., Holtzman, D. M., Crystal, R. G., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.04.020 · Cited by 107
“The major physiological differences between APOE3, the most common isoform, and APOE2 and APOE4, are due to differences in amino acids at 1 of 2 positions, residues 112 (APOE4) and 158 (APOE2), which are cysteine-arginine interchanges (Hatters et al., 2006).”
The Potential Therapeutic Application of Peptides and Peptidomimetics in Cardiovascular Disease
Recio, C., Μaione, F., Iqbal, A. J., Mascolo, N., & Feo, V. D. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00526 · Cited by 109
“It also plays a crucial role in the regulation of plasma cholesterol levels, given that it contains an LDL binding domain in its structure (Hatters et al., 2006; Mahley et al., 2006).”
BackgroundVerdegem, D., Badillo, A., Wieruszeski, J., Landrieu, I., Leroy, A., Bartenschlager, R. F. W., Pénin, F., Lippens, G. M., & Hanoulle, X. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.182436 · Cited by 105
Jeong, W., Lee, H. G., Cho, S., & Seo, J. (2019) · PubMed · doi:10.14348/molcells.2019.0200 · Cited by 104
“Among isoforms, ApoE4 displays lower transport affinity and binding capacity for lipids (Hatters et al., 2006; Vance, 2012), which could reduce cholesterol transport from astrocytes to neurons.”
BackgroundAPOE p.Leu167del mutation in familial hypercholesterolemia
Awan, Z. A., Choi, H. Y., Stitziel, N. O., Ruel, I. L., Bamimore, M. A., Husa, R., Gagnon, M.-H., Wang, R.-H. L., Peloso, G. M., Hegele, R. A., et al. (2013) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2013.09.007 · Cited by 115
Alzheimer’s Disease: Mechanism and Approach to Cell Therapy
Amemori, T., Jendelová, P., Růžička, J., Urdzíková, L. M., & Syková, E. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161125961 · Cited by 110
“APOE has a receptor-binding site in its N-terminal domain and a lipid-binding site in its C-terminal domain [268].”
BackgroundApolipoprotein E, amyloid-beta, and neuroinflammation in Alzheimer’s disease
Dorey, E., Chang, N., Liu, Q. Y., Yang, Z., & Zhang, W. (2014) · Neuroscience Bulletin · doi:10.1007/s12264-013-1422-z · Cited by 105
“hydrophobic lipid core with surface ApoE proteins wrapped around polar lipid head groups ([39]).”
InfluentialHuang, R. Y.-C., Garai, K., Frieden, C., & Gross, M. L. (2011) · Biochemistry · doi:10.1021/bi2010027 · Cited by 97
Lipid metabolism and neuroinflammation in Alzheimer’s disease: a role for liver X receptors
Kang, J., & Rivest, S. (2012) · Endocrine Reviews · doi:10.1210/er.2011-1049 · Cited by 94
Roles of ApoE4 on the Pathogenesis in Alzheimer’s Disease and the Potential Therapeutic Approaches
Sun, Y.-Y., Wang, Z., & Huang, H. (2023) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-023-01365-1 · Cited by 102
Simon, R., Girod, M., Fonbonne, C., Salvador, A., Clément, Y., Lantéri, P., Amouyel, P., Lambert, J. C., & Lemoine, J. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.018861 · Cited by 92
“Apolipoprotein E (ApoE) is a 299-amino acid protein associated with lipoproteins in the plasma and the cerebrospinal fluid (1).”
BackgroundJendresen, C., Årskog, V., Daws, M. R., & Nilsson, L. N. G. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0835-4 · Cited by 94
“Importantly, we report the first evidence that a TREM2-binding domain is found in amino acids 130–149 of human ApoE, which is the conserved receptor-binding domain in the main ApoE isoforms, ε2, ε3, and ε4, as reviewed in [48].”
BackgroundInvolvement of apolipophorin III in antibacterial defense of Galleria mellonella larvae
Zdybicka‐Barabas, A., & Cytryńska, M. (2010) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2010.10.001 · Cited by 91
Mazumdar, B., Banerjee, A. K., Meyer, K., & Ray, R. (2011) · Hepatology · doi:10.1002/hep.24523 · Cited by 91
“It is likely that an affinity of E1 for apolipoproteins directs the HCV E1-G pseudotype virus toward LDL-R, driven, of course, by the binding of apolipoproteins with LDL-R mediated by oppositely charged residues on the interacting proteins.(33,34) The fact that E2 lacks this affinity may explain that the HCV E2-G pseu…”
BackgroundStructure of saposin A lipoprotein discs
Popovic, K., Holyoake, J., Pomès, R., & Privé, G. G. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1115743109 · Cited by 90
Dietary fats, cerebrovasculature integrity and Alzheimer’s disease risk
Takechi, R., Galloway, S., Pallebage‐Gamarallage, M. M., Lam, V., & Mamo, J. C. L. (2009) · Progress in Lipid Research · doi:10.1016/j.plipres.2009.10.004 · Cited by 89
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Yao, Z., Qi, W., Zhang, H., Zhang, Z., Liu, L., Shao, Y., Zeng, H., Yin, J., Pan, H., Guo, X., et al. (2023) · eLife · doi:10.7554/elife.83069 · Cited by 88
“Apoe plays an important role in maintaining the normal levels of cholesterol and triglycerides in serum by transporting lipids in the blood ( Hatters et al., 2006 ).”
The APOE ε4 allele increases the risk of impaired spatial working memory in obstructive sleep apnea
Cosentino, F., Bosco, P., Drago, V., Prestianni, G., Lanuzza, B., Iero, I., Tripodi, M., Spada, R. S., Toscano, G., Caraci, F., et al. (2008) · Sleep Medicine · doi:10.1016/j.sleep.2007.10.015 · Cited by 84
“Additionally, research has described how e4 is related with elevated total cholesterol, atherosclerotic disease [70], and vascular dementia [71], all diseases that might have an impact on small vessels serving white matter.”
BackgroundZhong, N., Ramaswamy, G., & Weisgraber, K. H. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.014464 · Cited by 87
Self-citationDifferent Apolipoproteins Impact Nanolipoprotein Particle Formation
Chromy, B. A., Arroyo, E. S., Blanchette, C., Bench, G., Benner, H., Cappuccio, J. A., Coleman, M. A., Henderson, P. T., Hinz, A. K., Kuhn, E. A., et al. (2007) · Journal of the American Chemical Society · doi:10.1021/ja074753y · Cited by 84
Jones, P. B., Adams, K. W., Rozkalne, A., Spires-Jones, T. L., Hshieh, T. T., Hashimoto, T., von Armin, C. A. F., Mielke, M., Bacskai, B. J., & Hyman, B. T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014586 · Cited by 84
“However, the difference between the two distances is small enough to suggest that ApoE might encapsulate Ab, in a similar fashion to the way in which it interacts with lipids [32].”
BackgroundVaillant, A. (2018) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.8b00156 · Cited by 83
APOE ε4 allele is associated with cognitive impairment in patients with multiple sclerosis
Shi, J., Zhao, C., Vollmer, T. R., Tyry, T. M., & Kuniyoshi, S. M. (2007) · Neurology · doi:10.1212/01.wnl.0000264004.62612.44 · Cited by 82
The Complex Role of Apolipoprotein E in Alzheimer’s Disease: an Overview and Update
Mahoney‐Sanchez, L., Belaidi, A. A., Bush, A. I., & Ayton, S. (2016) · Journal of Molecular Neuroscience · doi:10.1007/s12031-016-0839-z · Cited by 84
“…or neuronmediated (Li et al. 2012) clearance of Aβ; (2) Aβ clearance via the blood-brain barrier (BBB) (Bachmeier et al. 2013); (3) Aβ clearance via the interstitial fluid or perivasculature (Castellano et al. 2011; Hawkes et al. 2012); and (4) proteolytic degradation of Aβ (Jiang et al. 2008).”
BackgroundFunctional insights from biophysical study of TREM2 interactions with apoE and Aβ 1‐42
Kober, D. L., Stuchell‐Brereton, M. D., Kluender, C. E., Dean, H. B., Strickland, M. R., Steinberg, D. F., Nelson, S. S., Baban, B. A., Holtzman, D. M., Frieden, C., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12194 · Cited by 86
“1-299); (2) C-term deletion (1-238); (3) C-term and partial hinge deletion (1-191); or (4) C-term and complete hinge deletion (1-169) (Figure 4.”
APOE and neuroenergetics: an emerging paradigm in Alzheimer's disease
Wolf, A. B., Caselli, R. J., Reiman, E. M., & Valla, J. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.10.011 · Cited by 84
Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients
Staquicini, F. I., Cardó‐Vila, M., Kolonin, M. G., Trepel, M., Edwards, J. K., Nunes, D. N., Сергеева, А., Efstathiou, E., Sun, J. D., Almeida, N. F., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114503108 · Cited by 79
“ApoE is a secreted protein that acts through the low-density lipoprotein receptor to mediate lipoprotein binding and catabolism (33).”
BackgroundApolipoprotein E4 domain interaction: Synaptic and cognitive deficits in mice
Zhong, N., Scearce-Levie, K. A., Ramaswamy, G., & Weisgraber, K. H. (2008) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2008.01.006 · Cited by 77
Self-citationGenetic influences on blood lipids and cardiovascular disease risk: tools for primary prevention
Ordovas, J. M. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.27113e · Cited by 74
Gau, B., Garai, K., Frieden, C., & Gross, M. L. (2011) · Biochemistry · doi:10.1021/bi200911c · Cited by 74
Metadata
- Authors
- Hatters, D. M., Peters-Libeu, C. A., & Weisgraber, K. H.
- Affiliations
- Gladstone Institutes (US)
- Corresponding author
- Weisgraber, Karl H.
- ORCID
- Hatters, Danny M.
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2006-08
- Volume
- 31
- Issue
- 8
- Pages
- 445-454
- ISSN
- 0968-0004 (ISSN-L)
- OpenAlex
- W2051394059
- Cited by
- 583
- References
- 88
- Citations by year
- 2026: 25 · 2025: 32 · 2024: 26 · 2023: 32 · 2022: 34 · 2021: 37 · 2020: 22 · 2019: 21 · 2018: 24 · 2017: 25 · 2016: 32 · 2015: 32 · 2014: 42 · 2013: 24 · 2012: 42
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG020235, P01AG022074)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein E, protein structure, APOE isoforms, low-density lipoprotein receptor family, lipid transport, atherosclerosis, Alzheimer's disease, neurodegenerative diseases, central nervous system, treatment options
- MeSH terms
- Animals, Apolipoproteins E, Humans, Models, Molecular, Protein Binding, Protein Folding, Neurodegenerative Diseases, Protein Isoforms, Atherosclerosis
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