본문 바로가기
KERD
논문KCI 등재

Cholesterol imbalance and neurotransmission defects in neurodegeneration

1

조회

0

다운로드

0

인용

0

참고문헌

주제분류생화학

초록

The brain contains the highest concentration of cholesterol in the human body, which emphasizes the importance of cholesterol in brain physiology. Cholesterol is involved in neurogenesis and synaptogenesis, and age-related reductions in cholesterol levels can lead to synaptic loss and impaired synaptic plasticity, which potentially contribute to neurodegeneration. The maintenance of cholesterol homeostasis in the neuronal plasma membrane is essential for normal brain function, and imbalances in cholesterol distribution are associated with various neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. This review aims to explore the molecular and pathological mechanisms by which cholesterol imbalance can lead to neurotransmission defects and neurodegeneration, focusing on four key mechanisms: (1) synaptic dysfunction, (2) alterations in membrane structure and protein clustering, (3) oligomers of amyloid beta (Aβ) protein, and (4) α-synuclein aggregation.

Abstract

The brain contains the highest concentration of cholesterol in the human body, which emphasizes the importance of cholesterol in brain physiology. Cholesterol is involved in neurogenesis and synaptogenesis, and age-related reductions in cholesterol levels can lead to synaptic loss and impaired synaptic plasticity, which potentially contribute to neurodegeneration. The maintenance of cholesterol homeostasis in the neuronal plasma membrane is essential for normal brain function, and imbalances in cholesterol distribution are associated with various neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. This review aims to explore the molecular and pathological mechanisms by which cholesterol imbalance can lead to neurotransmission defects and neurodegeneration, focusing on four key mechanisms: (1) synaptic dysfunction, (2) alterations in membrane structure and protein clustering, (3) oligomers of amyloid beta (Aβ) protein, and (4) α-synuclein aggregation.

참고문헌 (88)

  1. Dietschy, J. M., "Cholesterol metabolism in the brain", Curr. Opin. Lipidol, 12, pp.105~112 (2001)
  2. Bjorkhem, I., "Brain cholesterol : long secret life behind a barrier", Arterioscler. Thromb. Vasc. Biol, 24, pp.806~815 (2004)
  3. Dietschy, J. M., "Thematic review series: brain lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal", J. Lipid Res, 45, pp.1375~1397 (2004)
  4. Pfrieger, F. W., "Cholesterol homeostasis and function in neurons of the central nervous system", Cell. Mol. Life Sci, 60, pp.1158~1171 (2003)
  5. Cartocci, V., "Can cholesterol metabolism modulation affect brain function and behavior?", J. Cell Physiol, 232, pp.281~286 (2017)
  6. Svennerholm, L., "Membrane lipids of adult humanbrain : lipid composition of frontal and temporal lobe in subjects of age 20to 100 years", J. Neurochem, 63, pp.1802~1811 (1994)
  7. Martin, M., "Brain cholesterol in normal and pathological aging", Biochim. Biophys. Acta, 1801, pp.934~944 (2010)
  8. Martin, M. G., "Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents", EMBO Mol. Med, 6, pp.902~917 (2014)
  9. Linetti, A., "Cholesterol reduction impairs exocytosis of synaptic vesicles", J. Cell Sci, 123, pp.595~605 (2010)
  10. Liu, Q., "Neuronal LRP1 knockout in adult mice leads to impaired brain lipid metabolism and progressive, age-dependent synapse loss and neurodegenera tion", J. Neurosci, 30, pp.17068~17078 (2010)
  11. Vance, J. E., "Dysregulation of cholesterol balance in the brain : contribution to neurodegenerative diseases", Dis. Model Mech, 5, pp.746~755 (2012)
  12. Dai, L., "Cholesterol metabolism in neurodegenerative diseases : molecular mechanisms and therapeutic targets", Mol. Neurobiol, 58, pp.2183~2201 (2021)
  13. Yoon, J. H., "Brain lipidomics: from functional landscape to clinical sig nificance", Sci. Adv, 8, pp.eadc9317~ (2022)
  14. Varma, V. R., "Abnormal brain cholesterol homeostasis in Alzheimer’s disease a targeted metabolomic and transcriptomic study", NPJ Aging Mech. Dis, 7, pp.11~ (2021)
  15. Lange, Y., "Active membrane cholesterol as a physiological effector", Chem. Phys. Lipids, 199, pp.74~93 (2016)
  16. Koudinov, A. R., "Essential role for cholesterol in synaptic plasticity and neuronal degeneration", FASEB J, 15, pp.1858~1860 (2001)
  17. Zhang, J., "Roles of cholesterol in vesicle fusion and motion", Biophys. J, 97, pp.1371~1380 (2009)
  18. Churchward, M. A., "Choles terol facilitates the native mechanism of Ca2+-triggered membrane fusion", J. Cell Sci, 118, pp.4833~4848 (2005)
  19. Mailman, T., "Inhibition of neuronal cholesterol bio synthesis with lovastatin leads to impaired synaptic vesicle release even in the presence of lipoproteins or geranylgeraniol", J. Neurochem, 119, pp.1002~1015 (2011)
  20. Teixeira, G., "Cholesterol as a key player in the balance of evoked and spontaneous glutamate release in rat brain cortical synaptosomes", Neurochem. Int, 61, pp.1151~1159 (2012)
  21. Mercer, A. J., "Regulation of presynaptic strength by controlling Ca2+ channel mobility : effects of cholesterol depletion on release at the cone ribbon synapse", J. Neurophysiol, 107, pp.3468~3478 (2012)
  22. Tarakanova, O. I., "The role of membrane cholesterol in neurotransmitter release from motor nerve terminals", Dokl. Biol. Sci. : Proc. Acad. Sci. USSR, Biol. Sci. Sect, 438, pp.138~140 (2011)
  23. Ali Moussa, H. Y., "Requirement of cholesterol for calcium-dependent vesicle fusion by strengthening synaptotagmin-1-induced membrane bending", Adv. Sci, 10, pp.e2206823~ (2023)
  24. Lipowsky, R., "Remodeling of membrane shape and topology by curvature elas ticity and membrane tension", Adv. Biol, 6, pp.e2101020~ (2022)
  25. Yang, S. T., "The role of cholesterol in membrane fusion", Chem. Phys. Lipids, 199, pp.136~143 (2016)
  26. Zhang, Z., "Membrane bending energy and fusion pore kinetics in Ca(2+)-triggered exocytosis", Biophys. J, 98, pp.2524~2534 (2010)
  27. Martens, S., "How synaptotagmin promotes membrane fusion", Science, 316, pp.1205~1208 (2007)
  28. Hui, E., "Synaptotagmin mediated bending of the target membrane is a critical step in Ca(2+)-regulated fusion", Cell, 138, pp.709~721 (2009)
  29. Herrick, D. Z., "Position of synaptotagmin I at the membrane interface : cooperative interactions of tandem C2 domains", Biochemistry, 45, pp.9668~9674 (2006)
  30. Ali Moussa, H. Y., "Electrostatic regulation of the cis-and trans membrane interactions of synaptotagmin-1", Sci. Rep, 12, pp.22407~ (2022)
  31. McMahon, H. T., "Membrane curvature in synaptic vesicle fusion and beyond", Cell, 140, pp.601~605 (2010)
  32. Sudhof, T. C., "Calcium control of neurotransmitter release", Cold Spring Harb. Perspect. Biol, 4, pp.a011353~ (2012)
  33. Melland, H., "Disorders of synaptic vesicle fusion machinery", J. Neurochem, 157, pp.130~164 (2021)
  34. Chernomordik, L., "Lipids in biological membrane fusion", J. Membr. Biol, 146, pp.1~14 (1995)
  35. Chen, Z., "The influence of cholesterol on phospholipid membrane curvature and bending elasticity", Biophys. J, 73, pp.267~276 (1997)
  36. Ivankin, A., "Cholesterol mediates membrane cur vature during fusion events", Phys. Rev. Lett, 108, pp.238103~ (2012)
  37. Kreutzberger, A. J., "High cholesterol obviates a pro longed hemifusion intermediate in fast SNARE-mediated membrane fusion", Biophys. J, 109, pp.319~329 (2015)
  38. Wu, L., "Cholesterol stabilizes recombinant exocytic fusion pores by altering membrane bending rigidity", Biophys. J, 120, pp.1367~1377 (2021)
  39. Jahn, R., "SNAREs-engines for membrane fusion", Nat. Rev. Mol. Cell Biol, 7, pp.631~643 (2006)
  40. Brunger, A. T., "Molecular mechanisms of fast neurotransmitter release", Annu Rev. Biophys, 47, pp.469~497 (2018)
  41. Laude, A. J., "Plasma membrane microdomains : organization, function and trafficking", Mol. Membr. Biol, 21, pp.193~205 (2004)
  42. Willmann, R., "Cholesterol and lipid microdomains stabilize the postsynapse at the neuromuscular junction", EMBO J, 25, pp.4050~4060 (2006)
  43. Korade, Z., "Lipid rafts, cholesterol, and the brain", Neuro pharmacology, 55, pp.1265~1273 (2008)
  44. Murray, D. H., "Clustering of syntaxin-1A in model membranes is modulated by phosphatidylinositol 4, 5-bisphosphate and cholesterol", Biochemistry, 48, pp.4617~4625 (2009)
  45. Sieber, J. J., "Anatomy and dynamics of a supramolecular membrane protein cluster", Science, 317, pp.1072~1076 (2007)
  46. Feringa, F. M., "Cholesterol and Alzheimer’s disease; from risk genes to pathological effects", Front. Aging Neurosci, 13, pp.690372~ (2021)
  47. Hampel, H., "The amyloid-beta pathway in Alzheimer’s disease", Mol. Psychiatry, 26, pp.5481~5503 (2021)
  48. Jack, C. R. Jr, "11 C PiB and structural MRI provide complementary information in imaging of Alzheimer’s disease and amnestic mild cognitive impairment", Brain, 131, pp.665~680 (2008)
  49. Zhao, J., "Targeting amyloidogenic processing of APP in Alzheimer’s disease", Front. Mol. Neurosci, 13, pp.137~ (2020)
  50. Capitini, C., "APP and Bace1 : differential effect of cholesterol enrichment on processing and plasma membrane mobility", iScience, 26, pp.106611~ (2023)
  51. Cordy, J. M., "Exclusively targeting beta-secretase to lipid rafts by GPI-anchor addition up-regulates beta site processing of the amyloid precursor protein", Proc. Natl Acad. Sci. USA, 100, pp.11735~11740 (2003)
  52. Wang, H., "Regulation of beta-amyloid production in neurons by astrocyte derived cholesterol", Proc. Natl Acad. Sci. USA (2021)[DOI]
  53. Stewart, K. L., "Amyloid plaques beyond Abeta : a survey of the diverse modulators of amyloid aggregation", Biophys. Rev, 9, pp.405~419 (2017)
  54. Gellermann, G. P., "Paired helical filaments contain small amounts of cholesterol, phosphatidylcholine and sphingolipids", Biol. Chem, 387, pp.1267~1274 (2006)
  55. Zhou, X., "Free cholesterol induces higher beta-sheet content in Abeta peptide oligomers by aromatic interaction with Phe19", PLoS ONE, 7, pp.e46245~ (2012)
  56. Fernandez-Perez, E. J., "Effect of cholesterol on membrane fluidity and association of abeta oligomers and subsequent neuronal damage : a double edged sword", Front. Aging Neurosci, 10, pp.226~ (2018)
  57. Rudajev, V., "Cholesterol as a key player in amyloid beta-mediated toxicity in Alzheimer’s disease", Front. Mol. Neurosci, 15, pp.937056~ (2022)
  58. Habchi, J., "Cholesterol catalyses Abeta42 aggregation through a hetero geneous nucleation pathway in the presence of lipid membranes", Nat. Chem, 10, pp.673~683 (2018)
  59. Michaels, T. C. T., "Dynamics of oligomer populations formed during the aggregation of Alzheimer’s Abeta42 peptide", Nat. Chem, 12, pp.445~451 (2020)
  60. Terakawa, M. S., "Impact of membrane curvature on amyloid aggregation", Biochim. Biophys. Acta Biomembr, 1860, pp.1741~1764 (2018)
  61. Sugiura, Y., "High membrane curvature enhances binding, conformational changes, and fibrillation of amyloid-beta on lipid bilayer surfaces", Langmuir, 31, pp.11549~11557 (2015)
  62. Tahirbegi, B., "A novel abeta(40)assembly at physiological concentration", Sci. Rep, 10, pp.9477~ (2020)
  63. Fabiani, C., "Alzheimer’s disease as a membrane disorder : spatial cross-talk among beta-amyloid peptides, nicotinic acetylcholine receptors and lipid rafts", Front. Cell. Neurosci, 13, pp.309~ (2019)
  64. Sahoo, A., "Effects of applied surface-tension on membrane-assisted Abeta aggregation", Phys. Chem. Chem. Phys, 23, pp.20627~20633 (2021)
  65. Hernandez, F., "Tau aggregation", Neuroscience, 518, pp.64~69 (2023)
  66. Thijssen, E. H., "Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer’s disease and frontotemporal lobar degeneration : a retrospective diagnostic performance study", Lancet Neurol, 20, pp.739~752 (2021)
  67. Wray, S., "Linking amyloid and tau pathology in Alzheimer’s disease : the role of membrane cholesterol in Abeta-mediated tau toxicity", J. Neurosci, 29, pp.9665~9667 (2009)
  68. Bok, E., "Role of the lipid membrane and membrane proteins in tau pathology", Front. Cell Dev. Biol, 9, pp.653815~ (2021)
  69. Sallaberry, C. A., "Tau and membranes : interactions that promote folding and condensation", Front. Cell Dev. Biol, 9, pp.725241~ (2021)
  70. Goux, W. J., "Analysis of the core components of Alzheimer paired helical filaments. A gas chromatography", mass spectrometry characterization of fatty acids, carbohydrates and long-chain bases, 1995, pp.366, 81~85
  71. Tuck, B. J., "Cholesterol determines the cytosolic entry and seeded aggre gation of tau", Cell Rep, 39, pp.110776~ (2022)
  72. El Mammeri, N., "Membrane-induced tau amyloid f ibrils", Commun. Biol, 6, pp.467~ (2023)
  73. Mahul-Mellier, A. L., "The process of Lewy body formation, rather than simply alpha-synuclein fibrillization, is one of the major drivers of neurodegeneration", Proc. Natl Acad. Sci. USA, 117, pp.4971~4982 (2020)
  74. Galvagnion, C., "Lipid vesicles trigger alpha-synuclein aggregation by sti mulating primary nucleation", Nat. Chem. Biol, 11, pp.229~234 (2015)
  75. den Jager, W. A., "Sphingomyelin in Lewy inclusion bodies in Parkinson’s disease", Arch. Neurol, 21, pp.615~619 (1969)
  76. Bosco, D. A., "Elevated levels of oxidized cholesterol metabolites in Lewy body disease brains accelerate alpha-synuclein fibrilization", Nat. Chem. Biol, 2, pp.249~253 (2006)
  77. Jakubec, M., "Cholesterol-containing lipid nanodiscs promote an alpha-synuclein binding mode that accelerates oligomerization", FEBS J, 288, pp.1887~1905 (2021)
  78. Qi, Z., "Influence of cholesterol on the membrane binding and conformation of alpha-synuclein", J. Phys. Chem. B, 127, pp.1956~1964 (2023)
  79. Husain, M. A., "APOE and Alzheimer’s disease: from lipid transport to physiopathology and therapeutics", Front. Neurosci, 15, pp.630502~ (2021)
  80. Marais, A. D., "Apolipoprotein E in lipoprotein metabolism, health and cardiovas cular disease", Pathology, 51, pp.165~176 (2019)
  81. Huang, Y. A., "ApoE2, ApoE3, and ApoE4 differentially stimulate APP transcription and abeta secretion", Cell, 168, pp.427~441 (2017)
  82. Di Battista, A. M., "Alzheimer’s disease genetic risk factor APOE-epsilon4 also affects normal brain function", Curr. Alzheimer Res, 13, pp.1200~1207 (2016)
  83. Raulin, A. C., "ApoE in Alzheimer’s disease : pathophysiology and therapeutic strategies", Mol. Neurodegener, 17, pp.72~ (2022)
  84. Dugger, B. N., "Pathology of neurodegenerative diseases", Cold Spring Harb. Perspect. Biol (2017)[DOI]
  85. Kacher, R., "Altered cholesterol homeostasis in Huntington’s disease", Front Aging Neurosci, 14, pp.797220~ (2022)
  86. Gao, X., "Cholesterol modifies huntingtin binding to, disruption of, and aggregation on lipid membranes", Biochemistry, 55, pp.92~102 (2016)
  87. Stonebraker, A. R., "Cholesterol impacts the formation of huntingtin", lipid complexes and subsequent aggregation, 2023, pp.32, e4642~
  88. Pineda-Torra, I., "Disrupted lipid metabolism in multiple sclerosis: a role for liver X receptors?", Front. Endocrinol, 12, pp.639757~ (2021)

관련 논문AI추천

이 간행물의 다른 논문 (218건)