Top

European Journal of Medical Research

Published in:

Open Access 01-12-2023 | Review

A comprehensive review of the family of very-long-chain fatty acid elongases: structure, function, and implications in physiology and pathology

Authors: Xiangyu Wang, Hao Yu, Rong Gao, Ming Liu, Wenli Xie

Published in: European Journal of Medical Research | Issue 1/2023

Abstract

Background

The very-long-chain fatty acid elongase (ELOVL) family plays essential roles in lipid metabolism and cellular functions. This comprehensive review explores the structural characteristics, functional properties, and physiological significance of individual ELOVL isoforms, providing insights into lipid biosynthesis, cell membrane dynamics, and signaling pathways.

Aim of review

This review aims to highlight the significance of the ELOVL family in normal physiology and disease development. By synthesizing current knowledge, we underscore the relevance of ELOVLs as potential therapeutic targets.

Key scientific concepts of review

We emphasize the association between dysregulated ELOVL expression and diseases, including metabolic disorders, skin diseases, neurodegenerative conditions, and cancer. The intricate involvement of ELOVLs in cancer biology, from tumor initiation to metastasis, highlights their potential as targets for anticancer therapies. Additionally, we discuss the prospects of using isoform-specific inhibitors and activators for metabolic disorders and cancer treatment. The identification of ELOVL-based biomarkers may advance diagnostics and personalized medicine.

Conclusion

The ELOVL family's multifaceted roles in lipid metabolism and cellular physiology underscore its importance in health and disease. Understanding their functions offers potential therapeutic avenues and personalized treatments.

Agostini M, Melino G. Targeting lipid metabolism in cancer: neuroblastoma. 2022;41(2):255–60. https://doi.org/10.1007/s10555-022-10040-8.CrossRef

Barabas P, Liu A, Xing W, Chen CK, Tong Z, Watt CB, et al. Role of ELOVL4 and very long-chain polyunsaturated fatty acids in mouse models of Stargardt type 3 retinal degeneration. Proc Natl Acad Sci USA. 2013;110(13):5181–6. https://doi.org/10.1073/pnas.1214707110.CrossRefPubMedPubMedCentral

Brunner PM, Israel A, Zhang N, Leonard A, Wen HC, Huynh T, et al. Early-onset pediatric atopic dermatitis is characterized by T(H)2/T(H)17/T(H)22-centered inflammation and lipid alterations. J Allergy Clin Immunol. 2018;141(6):2094–106. https://doi.org/10.1016/j.jaci.2018.02.040.CrossRefPubMed

Burdge GC, Calder PC. Introduction to fatty acids and lipids. World Rev Nutr Diet. 2015;112:1–16. https://doi.org/10.1159/000365423.CrossRefPubMed

Carmona-Antonanzas G, Tocher DR, Martinez-Rubio L, Leaver MJ. Conservation of lipid metabolic gene transcriptional regulatory networks in fish and mammals. Gene. 2014;534(1):1–9. https://doi.org/10.1016/j.gene.2013.10.040.CrossRefPubMed

Castellini C, Mattioli S, Moretti E, Cotozzolo E, Perini F, Dal Bosco A, et al. Expression of genes and localization of enzymes involved in polyunsaturated fatty acid synthesis in rabbit testis and epididymis. Sci Rep. 2022;12(1):2637. https://doi.org/10.1038/s41598-022-06700-y.CrossRefPubMedPubMedCentral

Currie E, Schulze A, Zechner R, Walther TC, Farese RV Jr. Cellular fatty acid metabolism and cancer. Cell Metab. 2013;18(2):153–61. https://doi.org/10.1016/j.cmet.2013.05.017.CrossRefPubMedPubMedCentral

de Antueno RJ, Knickle LC, Smith H, Elliot ML, Allen SJ, Nwaka S, Winther MD. Activity of human Delta5 and Delta6 desaturases on multiple n-3 and n-6 polyunsaturated fatty acids. FEBS Lett. 2001;509(1):77–80. https://doi.org/10.1016/s0014-5793(01)03135-0.CrossRefPubMed

de Carvalho C, Caramujo MJ. The various roles of fatty acids. Molecules. 2018;23:10. https://doi.org/10.3390/molecules23102583.CrossRef

10.

de la Garza Puentes A, Montes Goyanes R, Chisaguano Tonato AM, Torres-Espinola FJ, Arias Garcia M, de Almeida L, et al. Association of maternal weight with FADS and ELOVL genetic variants and fatty acid levels- The PREOBE follow-up. PLoS ONE. 2017;12(6):e0179135. https://doi.org/10.1371/journal.pone.0179135.CrossRefPubMedPubMedCentral

11.

Diociaiuti, A., Martinelli, D., & Nicita, F. (2021). Two italian patients with ELOVL4-related neuro-ichthyosis: expanding the genotypic and phenotypic spectrum and ultrastructural characterization. 12:3. doi: https://doi.org/10.3390/genes12030343

12.

Dyall SC, Balas L, Bazan NG, Brenna JT, Chiang N, da Costa Souza F, et al. Polyunsaturated fatty acids and fatty acid-derived lipid mediators: recent advances in the understanding of their biosynthesis, structures, and functions. Prog Lipid Res. 2022;86:101165. https://doi.org/10.1016/j.plipres.2022.101165.CrossRefPubMedPubMedCentral

13.

Ellezam B, Kaseka ML, Nguyen DK, Michaud J. SCA34 caused by ELOVL4 L168F mutation is a lysosomal lipid storage disease sharing pathology features with neuronal ceroid lipofuscinosis and peroxisomal disorders. Acta Neuropathol. 2023;146(2):337–52. https://doi.org/10.1007/s00401-023-02582-0.CrossRefPubMed

14.

Fantini J. Lipid rafts and human diseases: why we need to target gangliosides. FEBS Open Bio. 2023. https://doi.org/10.1002/2211-5463.13612.CrossRefPubMedPubMedCentral

15.

Foko Kuate CA, Ebenhoh O, Bakker BM, Raguin A. Kinetic data for modeling the dynamics of the enzymes involved in animal fatty acid synthesis. Biosci Rep. 2023;43:7. https://doi.org/10.1042/BSR20222496.CrossRef

16.

Garcia-Corrales, A. V., Verberk, S. G., & Haidar, M. (2023) Fatty acid elongation by ELOVL6 hampers remyelination by promoting inflammatory foam cell formation during demyelination. 120(37), e2301030120. doi: https://doi.org/10.1073/pnas.2301030120

17.

Hu T, Zhang H, Du Y, Luo S, Yang X, Zhang H, et al. ELOVL2 restrains cell proliferation, migration, and invasion of prostate cancer via regulation of the tumor suppressor INPP4B. Cell Signal. 2022;96:110373. https://doi.org/10.1016/j.cellsig.2022.110373.CrossRefPubMed

18.

Iizuka K, Takao K, Yabe D. ChREBP-mediated regulation of lipid metabolism: involvement of the gut microbiota, liver, and adipose tissue. Front Endocrinol (Lausanne). 2020;11: 587189. https://doi.org/10.3389/fendo.2020.587189.CrossRefPubMed

19.

Ishihara N, Suzuki S, Tanaka S, Watanabe Y, Nagayama D, Saiki A, et al. Atorvastatin increases Fads1, Fads2 and Elovl5 gene expression via the geranylgeranyl pyrophosphate-dependent Rho kinase pathway in 3T3-L1 cells. Mol Med Rep. 2017;16(4):4756–62. https://doi.org/10.3892/mmr.2017.7141.CrossRefPubMedPubMedCentral

20.

Isokawa M, Sassa T, Hattori S, Miyakawa T, Kihara A. Reduced chain length in myelin sphingolipids and poorer motor coordination in mice deficient in the fatty acid elongase Elovl1. FASEB Bioadv. 2019;1(12):747–59. https://doi.org/10.1096/fba.2019-00067.CrossRefPubMedPubMedCentral

21.

Jörgensen JA, Zadravec D, Jacobsson A. Norepinephrine and rosiglitazone synergistically induce Elovl3 expression in brown adipocytes. Am J Physiol Endocrinol Metab. 2007;293(5):E1159-1168. https://doi.org/10.1152/ajpendo.00213.2007.CrossRefPubMed

22.

Jakobsson A, Westerberg R, Jacobsson A. Fatty acid elongases in mammals: their regulation and roles in metabolism. Prog Lipid Res. 2006;45(3):237–49. https://doi.org/10.1016/j.plipres.2006.01.004.CrossRefPubMed

23.

Kieu, T. L., Pierre, L., Derangère, V., Perrey, S., Truntzer, C., Jalil, A., et al. (2022). Downregulation of Elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of TGF-β receptors. 13(9), 758. doi: https://doi.org/10.1038/s41419-022-05209-6

24.

Kitazawa H, Miyamoto Y, Shimamura K, Nagumo A, Tokita S. Development of a high-density assay for long-chain fatty acyl-CoA elongases. Lipids. 2009;44(8):765–73. https://doi.org/10.1007/s11745-009-3320-8.CrossRefPubMed

25.

Kong, L., Dawkins, E., Campbell, F., Winkler, E., Derks, R. J. E., Giera, M., . . . Kros, A. (2020). Photo-controlled delivery of very long chain fatty acids to cell membranes and modulation of membrane protein function. Biochim Biophys Acta Biomembr, 1862(5), 183200. doi: https://doi.org/10.1016/j.bbamem.2020.183200

26.

Kyselova L, Vitova M, Rezanka T. Very long chain fatty acids. Prog Lipid Res. 2022;87: 101180. https://doi.org/10.1016/j.plipres.2022.101180.CrossRefPubMed

27.

Lai, K. Z. H., Yehia, N. A., Semnani-Azad, Z., Mejia, S. B., Boucher, B. A., Malik, V., . . . Hanley, A. J. (2023). Lifestyle Factors Associated with Circulating Very Long-Chain Saturated Fatty Acids in Humans: A Systematic Review of Observational Studies. Adv Nutr, 14(1), 99–114. doi: https://doi.org/10.1016/j.advnut.2022.10.004

28.

Li, X., Wang, J., Wang, L., Gao, Y., Feng, G., Li, G., . . . Ouyang, H. (2022). Lipid metabolism dysfunction induced by age-dependent DNA methylation accelerates aging. 7(1), 162. doi: https://doi.org/10.1038/s41392-022-00964-6

29.

Liu Y, Wang F, Yu XL, Miao ZM, Wang ZC, Chen Y, Wang YG. Genetic analysis of the ELOVL6 gene polymorphism associated with type 2 diabetes mellitus. Braz J Med Biol Res. 2013;46(7):623–8. https://doi.org/10.1590/1414-431x20133103.CrossRefPubMedPubMedCentral

30.

Luo J, Yang H. Mechanisms and regulation of cholesterol homeostasis. 2020;21(4):225–45. https://doi.org/10.1038/s41580-019-0190-7.CrossRef

31.

Macášek, J., & Zeman, M. (2021). Altered Indices of Fatty Acid Elongases ELOVL6, ELOVL5, and ELOVL2 Activities in Patients with Impaired Fasting Glycemia. 19(7), 386–392. doi: https://doi.org/10.1089/met.2021.0012

32.

Macasek J, Zeman M, Zak A, Stankova B, Vecka M. Altered indices of fatty acid elongases ELOVL6, ELOVL5, and ELOVL2 activities in patients with impaired fasting glycemia. Metab Syndr Relat Disord. 2021;19(7):386–92. https://doi.org/10.1089/met.2021.0012.CrossRefPubMed

33.

Malik K, He H, Huynh TN, Tran G, Mueller K, Doytcheva K, et al. Ichthyosis molecular fingerprinting shows profound T(H)17 skewing and a unique barrier genomic signature. J Allergy Clin Immunol. 2019;143(2):604–18. https://doi.org/10.1016/j.jaci.2018.03.021.CrossRefPubMed

34.

Matsuzaka, T., Kuba, M., Koyasu, S., Yamamoto, Y., Motomura, K., Arulmozhiraja, S, et al.. (2020). Hepatocyte ELOVL Fatty Acid Elongase 6 Determines Ceramide Acyl-Chain Length and Hepatic Insulin Sensitivity in Mice. 71(5), 1609–1625. doi: https://doi.org/10.1002/hep.30953

35.

Matsuzaka T, Kuba M, Koyasu S, Yamamoto Y, Motomura K, Arulmozhiraja S, et al. Hepatocyte ELOVL fatty acid elongase 6 determines ceramide acyl-chain length and hepatic insulin sensitivity in mice. Hepatology. 2020;71(5):1609–25. https://doi.org/10.1002/hep.30953.CrossRefPubMed

36.

Matsuzaka T, Shimano H. Role of fatty acid elongase Elovl6 in the regulation of fatty acid quality and lifestyle-related diseases. Yakugaku Zasshi. 2022;142(5):473–6. https://doi.org/10.1248/yakushi.21-00176-4.CrossRefPubMed

37.

Molino D, Galli T. Biogenesis and transport of membrane domains-potential implications in brain pathologies. Biochimie. 2014;96:75–84. https://doi.org/10.1016/j.biochi.2013.09.014.CrossRefPubMed

38.

Monirujjaman M, Pant A, Nelson R, Bathe O, Jacobs R, Mazurak VC. Alterations in hepatic fatty acids reveal depletion of total polyunsaturated fatty acids following irinotecan plus 5-fluorouracil treatment in an animal model of colorectal cancer. Prostaglandins Leukot Essent Fatty Acids. 2021;174: 102359. https://doi.org/10.1016/j.plefa.2021.102359.CrossRefPubMed

39.

Morigny P, Houssier M, Mairal A, Ghilain C, Mouisel E, Benhamed F, et al. Interaction between hormone-sensitive lipase and ChREBP in fat cells controls insulin sensitivity. Nat Metab. 2019;1(1):133–46. https://doi.org/10.1038/s42255-018-0007-6.CrossRefPubMed

40.

Motoi Y, Ito Z, Suzuki S, Takami S, Matsuo K, Sato M, et al. FADS2 and ELOVL6 mutation frequencies in Japanese Crohn’s disease patients. Drug Discov Ther. 2019;13(6):354–9. https://doi.org/10.5582/ddt.2019.01081.CrossRefPubMed

41.

Mueller N, Sassa T, Morales-Gonzalez S, Schneider J, Salchow DJ, Seelow D, Knierim E, Stenzel W, Kihara A, Schuelke M. De novo mutation in ELOVL1 causes ichthyosis, acanthosis nigricans, hypomyelination, spastic paraplegia, high frequency deafness and optic atrophy. J Med Genet. 2019;56(3):164–75. https://doi.org/10.1136/jmedgenet-2018-105711.CrossRefPubMed

42.

Nie L, Pascoa TC, Pike ACW, Bushell SR, Quigley A, Ruda GF, et al. The structural basis of fatty acid elongation by the ELOVL elongases. Nat Struct Mol Biol. 2021;28(6):512–20. https://doi.org/10.1038/s41594-021-00605-6.CrossRefPubMedPubMedCentral

43.

Nikulin S, Razumovskaya A, Poloznikov A, Zakharova G, Alekseev B, Tonevitsky A. ELOVL5 and IGFBP6 genes modulate sensitivity of breast cancer cells to ferroptosis. Front Mol Biosci. 2023;10:1075704. https://doi.org/10.3389/fmolb.2023.1075704.CrossRefPubMedPubMedCentral

44.

Nitta S, Kandori S, Tanaka K, Sakka S, Siga M, Nagumo Y, Negoro H, Kojima T, Mathis BJ, Shimazui T, Miyamoto T. ELOVL5-mediated fatty acid elongation promotes cellular proliferation and invasion in renal cell carcinoma. Cancer Sci. 2022;113(8):2738. https://doi.org/10.1111/cas.15454.CrossRefPubMedPubMedCentral

45.

Ohno Y, Suto S, Yamanaka M, Mizutani Y, Mitsutake S, Igarashi Y, et al. ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis. Proc Natl Acad Sci U S A. 2010;107(43):18439–44. https://doi.org/10.1073/pnas.1005572107.CrossRefPubMedPubMedCentral

46.

Pei X, Qi D, Liu J, Si H, Huang S, Zou S, et al. Screening marker genes of type 2 diabetes mellitus in mouse lacrimal gland by LASSO regression. Sci Rep. 2023;13(1):6862. https://doi.org/10.1038/s41598-023-34072-4.CrossRefPubMedPubMedCentral

47.

Posor Y, Jang W. Phosphoinositides as membrane organizers. 2022;23(12):797–816. https://doi.org/10.1038/s41580-022-00490-x.CrossRef

48.

Radmark O. Formation of eicosanoids and other oxylipins in human macrophages. Biochem Pharmacol. 2022;204: 115210. https://doi.org/10.1016/j.bcp.2022.115210.CrossRefPubMed

49.

Risha MA, Ali A, Siengdee P, Trakooljul N, Dannenberger D, Wimmers K, Ponsuksili S. Insights into molecular pathways and fatty acid membrane composition during the temperature stress response in the murine C2C12 cell model. Sci Total Environ. 2022;807(Pt 3): 151019. https://doi.org/10.1016/j.scitotenv.2021.151019.CrossRefPubMed

50.

Robichaud PP, Munganyiki JE, Boilard E, Surette ME. Polyunsaturated fatty acid elongation and desaturation in activated human T-cells: ELOVL5 is the key elongase. J Lipid Res. 2018;59(12):2383–96. https://doi.org/10.1194/jlr.M090050.CrossRefPubMedPubMedCentral

51.

Rugolo F, Bazan NG, Calandria J, Jun B, Raschella G, Melino G, Agostini M. The expression of ELOVL4, repressed by MYCN, defines neuroblastoma patients with good outcome. Oncogene. 2021;40(38):5741–51. https://doi.org/10.1038/s41388-021-01959-3.CrossRefPubMed

52.

Sassa T, Kihara A. Metabolism of very long-chain Fatty acids: genes and pathophysiology. Biomol Ther (Seoul). 2014;22(2):83–92. https://doi.org/10.4062/biomolther.2014.017.CrossRefPubMed

53.

Sassa T, Ohno Y, Suzuki S, Nomura T, Nishioka C, Kashiwagi T, Kihara A. Impaired epidermal permeability barrier in mice lacking elovl1, the gene responsible for very-long-chain fatty acid production. Mol Cell Biol. 2013;33(14):2787–96. https://doi.org/10.1128/mcb.00192-13.CrossRefPubMedPubMedCentral

54.

Sassa T, Wakashima T, Ohno Y, Kihara A. Lorenzo’s oil inhibits ELOVL1 and lowers the level of sphingomyelin with a saturated very long-chain fatty acid. J Lipid Res. 2014;55(3):524–30. https://doi.org/10.1194/jlr.M044586.CrossRefPubMedPubMedCentral

55.

Seebacher F, Zeigerer A, Kory N, Krahmer N. Hepatic lipid droplet homeostasis and fatty liver disease. Semin Cell Dev Biol. 2020;108:72–81. https://doi.org/10.1016/j.semcdb.2020.04.011.CrossRefPubMed

56.

Shimano H. SREBP-1c and Elovl6 as targets for obesity-related disorders. Yakugaku Zasshi. 2015;135(9):1003–9. https://doi.org/10.1248/yakushi.15-00175-1.CrossRefPubMed

57.

Slieker RC, Relton CL, Gaunt TR, Slagboom PE, Heijmans BT. Age-related DNA methylation changes are tissue-specific with ELOVL2 promoter methylation as exception. Epigenetics Chromatin. 2018;11(1):25. https://doi.org/10.1186/s13072-018-0191-3.CrossRefPubMedPubMedCentral

58.

Su YC, Feng YH, Wu HT, Huang YS, Tung CL, Wu P, et al. Elovl6 is a negative clinical predictor for liver cancer and knockdown of Elovl6 reduces murine liver cancer progression. Sci Rep. 2018;8(1):6586. https://doi.org/10.1038/s41598-018-24633-3.CrossRefPubMedPubMedCentral

59.

Tamura K, Makino A, Hullin-Matsuda F, Kobayashi T, Furihata M, Chung S, et al. Novel lipogenic enzyme ELOVL7 is involved in prostate cancer growth through saturated long-chain fatty acid metabolism. Cancer Res. 2009;69(20):8133–40. https://doi.org/10.1158/0008-5472.can-09-0775.CrossRefPubMed

60.

Tanno H, Sassa T, Sawai M, Kihara A. Production of branched-chain very-long-chain fatty acids by fatty acid elongases and their tissue distribution in mammals. Biochim Biophys Acta Mol Cell Biol Lipids. 2021;1866(1): 158842. https://doi.org/10.1016/j.bbalip.2020.158842.CrossRefPubMed

61.

Tian X, Li S, Ge G. Apatinib promotes ferroptosis in colorectal cancer cells by targeting ELOVL6/ACSL4 signaling. Cancer Manag Res. 2021;13:1333–42. https://doi.org/10.2147/cmar.s274631.CrossRefPubMedPubMedCentral

62.

Uchida Y, Holleran WM. Omega-O-acylceramide, a lipid essential for mammalian survival. J Dermatol Sci. 2008;51(2):77–87. https://doi.org/10.1016/j.jdermsci.2008.01.002.CrossRefPubMed

63.

Walther TC, Chung J, Farese RV Jr. Lipid droplet biogenesis. Annu Rev Cell Dev Biol. 2017;33:491–510. https://doi.org/10.1146/annurev-cellbio-100616-060608.CrossRefPubMedPubMedCentral

64.

Wang Y, Botolin D, Christian B, Busik J, Xu J, Jump DB. Tissue-specific, nutritional, and developmental regulation of rat fatty acid elongases. J Lipid Res. 2005;46(4):706–15. https://doi.org/10.1194/jlr.M400335-JLR200.CrossRefPubMed

65.

Wei M, Li P, Guo K. The impact of PSRC1 overexpression on gene and transcript expression profiling in the livers of ApoE(-/-) mice fed a high-fat diet. Mol Cell Biochem. 2020;465(1–2):125–39. https://doi.org/10.1007/s11010-019-03673-x.CrossRefPubMed

66.

Yang Y, Chen Z, Zhou L, Wu G, Ma X, Zheng Y, et al. In silico development and validation of a novel glucose and lipid metabolism-related gene signature in gastric cancer. Transl Cancer Res. 2022;11(7):1977–93. https://doi.org/10.21037/tcr-22-168.CrossRefPubMedPubMedCentral

67.

Yang Y, Liu L, Li M, Cheng X, Fang M, Zeng Q, Xu Y. The chromatin remodeling protein BRG1 links ELOVL3 trans-activation to prostate cancer metastasis. Biochim Biophys Acta Gene Regul Mech. 2019;1862(8):834–45. https://doi.org/10.1016/j.bbagrm.2019.05.005.CrossRefPubMed

68.

Yeboah GK, Lobanova ES, Brush RS, Agbaga MP. Very long chain fatty acid-containing lipids: a decade of novel insights from the study of ELOVL4. J Lipid Res. 2021;62: 100030. https://doi.org/10.1016/j.jlr.2021.100030.CrossRefPubMedPubMedCentral

69.

Zhang Y, Pang S, Sun B, Zhang M, Jiao X, Lai L, et al. ELOVLs predict distinct prognosis value and immunotherapy efficacy in patients with hepatocellular carcinoma. Front Oncol. 2022;12: 884066. https://doi.org/10.3389/fonc.2022.884066.CrossRefPubMedPubMedCentral

Title: A comprehensive review of the family of very-long-chain fatty acid elongases: structure, function, and implications in physiology and pathology
Authors: Xiangyu Wang
Hao Yu
Rong Gao
Ming Liu
Wenli Xie
Publication date: 01-12-2023
Publisher: BioMed Central
Published in: European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI: https://doi.org/10.1186/s40001-023-01523-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A comprehensive review of the family of very-long-chain fatty acid elongases: structure, function, and implications in physiology and pathology

Abstract

Background

Aim of review

Key scientific concepts of review

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Aim of review

Key scientific concepts of review

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2023

Functional independence, frailty and perceived quality of life in patients who developed delirium during ICU stay: a prospective cohort study

Evaluating safety risks of whole-body cryotherapy/cryostimulation (WBC): a scoping review from an international consortium

Evaluation of three scoring systems for predicting renal prognosis in antineutrophil cytoplasmic antibody-associated glomerulonephritis

Lifestyle factors, metabolic factors and socioeconomic status for pelvic organ prolapse: a Mendelian randomization study

Bacterial pathogens and in-hospital mortality in revision surgery for periprosthetic joint infection of the hip and knee: analysis of 346 patients

Current clinical presentations of AIDS dementia in a tropical environment: study of 26 observations in the neurology department of the University Hospital of Conakry