Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Thay đổi mức lipid cung cấp bằng chứng cho rối loạn myelin trong thoái hóa thần kinh đa hệ thống
Tóm tắt
Bệnh thoái hóa thần kinh đa hệ thống (MSA) là một bệnh tiến triển nhanh chóng, được đặc trưng bởi hiện tượng parkinson, loạn điều phối tiểu não và thất bại tự động. Một dấu ấn bệnh lý của MSA là sự hiện diện của các tinh thể α-synuclein trong các tế bào oligodendrocyte, các tế bào hỗ trợ sản xuất myelin trong não. Bệnh lý não và các nghiên cứu trong ống nghiệm chỉ ra rằng sự không ổn định của myelin có thể là một sự kiện sớm trong bệnh sinh của MSA. Lipid là thành phần chính (78% w/w) của myelin và đã được cho là có liên quan đến rối loạn myelin trong MSA. Tuy nhiên, các thay đổi, nếu có, về mức độ/phân phối lipid trong não MSA vẫn chưa được biết đến. Tại đây, chúng tôi thực hiện một phân tích toàn diện về myelin trong MSA. Chúng tôi đã đo lường một cách định lượng ba nhóm lipid, sphingomyelin, sulfatide và galactosylceramide, tất cả đều quan trọng trong tính toàn vẹn và chức năng của myelin, ở các vùng trắng bị ảnh hưởng (dưới vỏ não vận động) và không bị ảnh hưởng (dưới vỏ não thị giác). Đối với cả ba nhóm lipid, phần lớn các loại lipid đều bị giảm nghiêm trọng (40–69%) trong chất trắng bị ảnh hưởng nhưng không bị ảnh hưởng của MSA. Phân tích sự phân bố của các loại lipid cho thấy không có sự thay đổi đáng kể nào trong độ dài/nội dung chuỗi axit béo với MSA. Sự giảm mức lipid đi kèm với sự gia tăng phát biểu của α-synuclein. Những dữ liệu này chỉ ra rằng mức độ tuyệt đối, chứ không phải phân phối, của lipid myelin đã bị thay đổi trong MSA, và cung cấp bằng chứng cho rối loạn lipid myelin trong bệnh lý MSA. Chúng tôi đề xuất rằng sự điều hòa sai lipid myelin trong quá trình bệnh sinh MSA có thể kích thích sự không ổn định của myelin.
Từ khóa
#bệnh thoái hóa thần kinh đa hệ thống #myelin #lipid #α-synuclein #loạn điều phối tiểu não #bệnh lý thần kinhTài liệu tham khảo
Bower JH, Maraganore DM, McDonnell SK, Rocca WA: Incidence of progressive supranuclear palsy and multiple system atrophy in Olmsted County, Minnesota, 1976 to 1990. Neurology 1997, 49: 1284–1288. 10.1212/WNL.49.5.1284
Schrag A, Ben-Shlomo Y, Quinn N: Prevalence of progressive supranuclear palsy and multiple system atrophy: a cross-sectional study. Lancet 1999, 354: 1771–1775. 10.1016/S0140-6736(99)04137-9
Schrag A, Wenning GK, Quinn N, Ben-Shlomo Y: Survival in multiple system atrophy. Mov Disord 2008, 23: 294–296. 10.1002/mds.21839
Papapetropoulos S, Tuchman A, Laufer D, Papatsoris AG, Papapetropoulos N, Mash DC: Causes of death in multiple system atrophy. J Neurol Neurosurg Psychiatry 2007, 78: 327–329. 10.1136/jnnp.2006.103929
Papp MI, Kahn JE, Lantos PL: Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci 1989, 94: 79–100. 10.1016/0022-510X(89)90219-0
Wenning G, Tison F, Ben Shlomo Y, Daniel S, Quinn N: Multiple system atrophy: a review of 203 pathologically proven cases. Mov Disord 1997, 12: 133–147. 10.1002/mds.870120203
Ozawa T: Morphological substrate of autonomic failure and neurohormonal dysfunction in multiple system atrophy: impact on determining phenotype spectrum. Acta Neuropathol 2007, 114: 201–211. 10.1007/s00401-007-0254-1
Ferguson B, Matyszak MK, Esiri MM, Perry VH: Axonal damage in acute multiple sclerosis lesions. Brain 1997, 120: 393–399. 10.1093/brain/120.3.393
Trapp BD, Nave K-A: Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci 2008, 31: 247–269. 10.1146/annurev.neuro.30.051606.094313
Wilkins A, Majed H, Layfield R, Compston A, Chandran S: Oligodendrocytes promote neuronal survival and axonal length by distinct intracellular mechanisms: a novel role for oligodendrocyte-derived glial cell line-derived neurotrophic factor. J Neurosci 2003, 23: 4967–4974.
Sailer A: First genome-wide association study in multiple system atrophy [abstract]. Mov Disord 2012, 27: 1425. 10.1002/mds.25029
Ozawa T, Takano H, Onodera O, Kobayashi H, Ikeuchi T, Koide R, Okuizumi K, Shimohata T, Wakabayashi K, Takahashi H, Tsuji S: No mutation in the entire coding region of the alpha-synuclein gene in pathologically confirmed cases of multiple system atrophy. Neurosci Lett 1999, 270: 110–112. 10.1016/S0304-3940(99)00475-9
Lincoln SJ, Ross OA, Milkovic NM, Dickson DW, Rajput A, Robinson CA, Papapetropoulos S, Mash DC, Farrer MJ: Quantitative PCR-based screening of [alpha]-synuclein multiplication in multiple system atrophy. Parkinsonism Relat Disord 2007, 13: 340–342. 10.1016/j.parkreldis.2006.12.005
Morris H, Vaughan J, Datta S, Bandopadhyay R, De Silva HAR, Schrag A, Cairns NJ, Burn D, Nath U, Lantos PL: Multiple system atrophy/progressive supranuclear palsy: α-synuclein, synphilin, tau, and APOE. Neurology 2000, 55: 1918–1920. 10.1212/WNL.55.12.1918
Song YJ, Lundvig DM, Huang Y, Gai WP, Blumbergs PC, Hojrup P, Otzen D, Halliday GM, Jensen PH: p25alpha relocalizes in oligodendroglia from myelin to cytoplasmic inclusions in multiple system atrophy. Am J Pathol 2007, 171: 1291–1303. 10.2353/ajpath.2007.070201
Marcus J, Honigbaum S, Shroff S, Honke K, Rosenbluth J, Dupree JL: Sulfatide is essential for the maintenance of CNS myelin and axon structure. Glia 2006, 53: 372–381. 10.1002/glia.20292
Bosio A, Binczek E, Haupt WF, Stoffel W: Composition and biophysical properties of myelin lipid define the neurological defects in galactocerebroside-and sulfatide-deficient mice. J Neurochem 1998, 70: 308–315. 10.1046/j.1471-4159.1998.70010308.x
Hanada K, Nishijima M, Akamatsu Y, Pagano RE: Both sphingolipids and cholesterol participate in the detergent insolubility of alkaline phosphatase, a glycosylphosphatidylinositol-anchored protein, in mammalian membranes. J Biol Chem 1995, 270: 6254–6260. 10.1074/jbc.270.20.11962
Scheiffele P, Roth MG, Simons K: Interaction of influenza virus haemagglutinin with sphingolipid-cholesterol membrane domains via its transmembrane domain. EMBO J 1997, 16: 5501–5508. 10.1093/emboj/16.18.5501
Kim WS, Hsiao J-HT, Bhatia S, Glaros EN, Don AS, Tsuruoka S, Shannon Weickert C, Halliday GM: ABCA8 stimulates sphingomyelin production in oligodendrocytes. Biochem J 2013, 452: 401–410. 10.1042/BJ20121764
O’Brien JS, Sampson EL: Lipid composition of the normal human brain: gray matter, white matter, and myelin. J Lipid Res 1965, 6: 537–544.
Bosio A, Binczek E, Stoffel W: Functional breakdown of the lipid bilayer of the myelin membrane in central and peripheral nervous system by disrupted galactocerebroside synthesis. Proc Natl Acad Sci 1996, 93: 13280–13285. 10.1073/pnas.93.23.13280
Coetzee T, Fujita N, Dupree J, Shi R, Blight A, Suzuki K, Suzuki K, Popko B: Myelination in the absence of galactocerebroside and sulfatide: normal structure with abnormal function and regional instability. Cell 1996, 86: 209–219. 10.1016/S0092-8674(00)80093-8
Wenning GK, Tison F, Seppi K, Sampaio C, Diem A, Yekhlef F, Ghorayeb I, Ory F, Galitzky M, Scaravilli T, Bozi M, Colosimo C, Gilman S, Shults CW, Quinn NP, Rascol O, Poewe W: Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS). Mov Disord 2004, 19: 1391–1402. 10.1002/mds.20255
Bielawski J, Szulc ZM, Hannun YA, Bielawska A: Simultaneous quantitative analysis of bioactive sphingolipids by high-performance liquid chromatography-tandem mass spectrometry. Methods 2006, 39: 82–91. 10.1016/j.ymeth.2006.05.004
Wong JW, Abuhusain HJ, McDonald KL, Don AS: MMSAT: automated quantification of metabolites in selected reaction monitoring experiments. Anal Chem 2012, 84: 470–474. 10.1021/ac2026578
Hejazi L, Wong JW, Cheng D, Proschogo N, Ebrahimi D, Garner B, Don AS: Mass and relative elution time profiling: two-dimensional analysis of sphingolipids in Alzheimer’s disease brains. Biochem J 2011, 438: 165–175. 10.1042/BJ20110566
Bleasel JM, Hsiao J-HT, Halliday GM, Kim WS: Increased expression of ABCA8 in multiple system atrophy brain is associated with changes in pathogenic proteins. J Parkinsons Dis 2013, 3: 331–339.
Gault CR, Obeid LM, Hannun YA: An overview of sphingolipid metabolism: from synthesis to breakdown. Adv Exp Med Biol 2010, 688: 1–23. 10.1007/978-1-4419-6741-1_1
Baumann N, Pham-Dinh D: Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiol Rev 2001, 81: 871–927.
Pewzner-Jung Y, Ben-Dor S, Futerman AH: When do Lasses (longevity assurance genes) become CerS (ceramide synthases)? Insights into the regulation of ceramide synthesis. J Biol Chem 2006, 281: 25001–25005. 10.1074/jbc.R600010200
Lahiri S, Futerman AH: LASS5 is a bona fide dihydroceramide synthase that selectively utilizes palmitoyl-CoA as acyl donor. J Biol Chem 2005, 280: 33735–33738. 10.1074/jbc.M506485200
Guillas I, Kirchman PA, Chuard R, Pfefferli M, Jiang JC, Jazwinski SM, Conzelmann A: C26-CoA-dependent ceramide synthesis of Saccharomyces cerevisiae is operated by Lag1p and Lac1p. EMBO J 2001, 20: 2655–2665. 10.1093/emboj/20.11.2655
Mizutani Y, Kihara A, Igarashi Y: Mammalian Lass6 and its related family members regulate synthesis of specific ceramides. Biochem J 2005, 390: 263–271. 10.1042/BJ20050291
Riebeling C, Allegood JC, Wang E, Merrill AH, Futerman AH: Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors. J Biol Chem 2003, 278: 43452–43459. 10.1074/jbc.M307104200
Venkataraman K, Riebeling C, Bodennec J, Riezman H, Allegood JC, Sullards MC, Merrill AH, Futerman AH: Upstream of growth and differentiation factor 1 (uog1), a mammalian homolog of the yeast Longevity Assurance Gene 1 (LAG1), regulatesN-Stearoyl-sphinganine (C18-(Dihydro) ceramide) synthesis in a fumonisin B1-independent manner in mammalian cells. J Biol Chem 2002, 277: 35642–35649. 10.1074/jbc.M205211200
Mizutani Y, Kihara A, Igarashi Y: LASS3 (longevity assurance homologue 3) is a mainly testis-specific (dihydro) ceramide synthase with relatively broad substrate specificity. Biochem J 2006, 398: 531–538. 10.1042/BJ20060379
Thomas RL, Matsko CM, Lotze MT, Amoscato AA: Mass spectrometric identification of increased C16 ceramide levels during apoptosis. J Biol Chem 1999, 274: 30580–30588. 10.1074/jbc.274.43.30580
Kroesen B-J, Jacobs S, Pettus BJ, Sietsma H, Kok JW, Hannun YA, de Leij LFMH: BcR-induced apoptosis involves differential regulation of C16 and C24-ceramide formation and sphingolipid-dependent activation of the proteasome. J Biol Chem 2003, 278: 14723–14731. 10.1074/jbc.M210756200
Ben-David O, Futerman AH: The role of the ceramide acyl chain length in neurodegeneration: involvement of ceramide synthases. Neuromolecular Med 2010, 12: 341–350. 10.1007/s12017-010-8114-x
Becker I, Wang-Eckhardt L, Yaghootfam A, Gieselmann V, Eckhardt M: Differential expression of (dihydro) ceramide synthases in mouse brain: oligodendrocyte-specific expression of CerS2/Lass2. Histochem Cell Biol 2008, 129: 233–241. 10.1007/s00418-007-0344-0
Imgrund S, Hartmann D, Farwanah H, Eckhardt M, Sandhoff R, Degen J, Gieselmann V, Sandhoff K, Willecke K: Adult ceramide synthase 2 (CERS2)-deficient mice exhibit myelin sheath defects, cerebellar degeneration, and hepatocarcinomas. J Biol Chem 2009, 284: 33549–33560. 10.1074/jbc.M109.031971
Campbell BC, McLean CA, Culvenor JG, Gai WP, Blumbergs PC, Jakala P, Beyreuther K, Masters CL, Li QX: The solubility of alpha-synuclein in multiple system atrophy differs from that of dementia with Lewy bodies and Parkinson’s disease. J Neurochem 2001, 76: 87–96. 10.1046/j.1471-4159.2001.00021.x
Culvenor JG, McLean CA, Cutt S, Campbell BC, Maher F, Jakala P, Hartmann T, Beyreuther K, Masters CL, Li QX: Non-Abeta component of Alzheimer’s disease amyloid (NAC) revisited. NAC and alpha-synuclein are not associated with Abeta amyloid. Am J Pathol 1999, 155: 1173–1181. 10.1016/S0002-9440(10)65220-0
Miller DW, Johnson JM, Solano SM, Hollingsworth ZR, Standaert DG, Young AB: Absence of alpha-synuclein mRNA expression in normal and multiple system atrophy oligodendroglia. J Neural Transm 2005, 112: 1613–1624. 10.1007/s00702-005-0378-1
Mori F, Tanji K, Yoshimoto M, Takahashi H, Wakabayashi K: Demonstration of alpha-synuclein immunoreactivity in neuronal and glial cytoplasm in normal human brain tissue using proteinase K and formic acid pretreatment. Exp Neurol 2002, 176: 98–104. 10.1006/exnr.2002.7929
Richter-Landsberg C, Gorath M, Trojanowski JQ, Lee VM: alpha-synuclein is developmentally expressed in cultured rat brain oligodendrocytes. J Neurosci Res 2000, 62: 9–14. 10.1002/1097-4547(20001001)62:1<9::AID-JNR2>3.0.CO;2-U
Kahle PJ, Neumann M, Ozmen L, Muller V, Jacobsen H, Spooren W, Fuss B, Mallon B, Macklin WB, Fujiwara H, Hasegawa M, Iwatsubo T, Kretzschmar HA, Haass C: Hyperphosphorylation and insolubility of alpha-synuclein in transgenic mouse oligodendrocytes. EMBO Rep 2002, 3: 583–588. 10.1093/embo-reports/kvf109
Stefanova N, Reindl M, Neumann M, Haass C, Poewe W, Kahle PJ, Wenning GK: Oxidative stress in transgenic mice with oligodendroglial alpha-synuclein overexpression replicates the characteristic neuropathology of multiple system atrophy. Am J Pathol 2005, 166: 869–876. 10.1016/S0002-9440(10)62307-3
Yazawa I, Giasson BI, Sasaki R, Zhang B, Joyce S, Uryu K, Trojanowski JQ, Lee VM: Mouse model of multiple system atrophy alpha-synuclein expression in oligodendrocytes causes glial and neuronal degeneration. Neuron 2005, 45: 847–859. 10.1016/j.neuron.2005.01.032
Lee HJ, Suk JE, Bae EJ, Lee SJ: Clearance and deposition of extracellular alpha-synuclein aggregates in microglia. Biochem Biophys Res Commun 2008, 372: 423–428. 10.1016/j.bbrc.2008.05.045
Lee HJ, Suk JE, Patrick C, Bae EJ, Cho JH, Rho S, Hwang D, Masliah E, Lee SJ: Direct transfer of alpha-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies. J Biol Chem 2010, 285: 9262–9272. 10.1074/jbc.M109.081125
Benes FM, Turtle M, Khan Y, Farol P: Myelination of a key relay zone in the hippocampal formation occurs in the human brain during childhood, adolescence, and adulthood. Arch Gen Psychiatry 1994, 51: 477–484. 10.1001/archpsyc.1994.03950060041004
Miller DJ, Duka T, Stimpson CD, Schapiro SJ, Baze WB, McArthur MJ, Fobbs AJ, Sousa AMM, Šestan N, Wildman DE: Prolonged myelination in human neocortical evolution. Proc Natl Acad Sci U S A 2012, 109: 16480–16485. 10.1073/pnas.1117943109
