Unesterified cholesterol accumulation in late endosomes/lysosomes causes neurodegeneration and is prevented by driving cholesterol export from this compartment

Journal of Neuroscience

Volumn 31, Issue 25, 2011, Pages 9404-9413

  Aqul, Amal ^a   Liu, Benny ^a   Ramirez, Charina M ^a   Pieper, Andrew A ^a   Estill, Sandi Jo ^a   Burns, Dennis K ^a   Liu, Bing ^a   Repa, Joyce J ^a   Turley, Stephen D ^a   Dietschy, John M ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 HYDROXYPROPYL BETA CYCLODEXTRIN; CHOLESTEROL; CHOLESTEROL ESTER; LIVER X RECEPTOR; STEROL REGULATORY ELEMENT BINDING PROTEIN 2;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CHOLESTEROL SYNTHESIS; CHOLESTEROL TRANSPORT; CONTINUOUS INFUSION; CONTROLLED STUDY; CYTOSOL; DRUG CLEARANCE; DRUG EFFECT; ENDOSOME; FEMALE; GENE ACTIVATION; LIPID STORAGE; LYSOSOME; MALE; MOUSE; NERVE DEGENERATION; NONHUMAN; PRIORITY JOURNAL;

ANIMALS; BIOLOGICAL TRANSPORT, ACTIVE; CHOLESTEROL; ENDOSOMES; ESTERIFICATION; LYSOSOMES; MICE; MICE, KNOCKOUT; NEURODEGENERATIVE DISEASES;

EID: 79959654327     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.1317-11.2011     Document Type: Article

References (41)

1. Beltroy EP, Liu B, Dietschy JM, Turley SD (2007) Lysosomal unesterified cholesterol content correlates with liver cell death in murine Niemann-Pick type C disease. J Lipid Res 48:869-881.
2. Carstea ED, Morris JA, Coleman KG, Loftus SK, Zhang D, Cummings C, Gu J, Rosenfeld MA, Pavan WJ, Krizman DB, Nagle J, Polymeropoulos MH, Sturley SL, Ioannou YA, Higgins ME, Comly M, Cooney A, Brown A, Kaneski CR, Blanchette-Mackie EJ, et al. (1997) Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis. Science 277:228-231.
3. Cavender CP, Turley SD, Dietschy JM (1995) Sterol metabolism in fetal, newborn, and suckled lambs and their response to cholesterol after weaning. Am J Physiol 269:E331-E340.
4. Chevallier J, Chamoun Z, Jiang G, Prestwich G, Sakai N, Matile S, Parton RG, Gruenberg J (2008) Lysobisphosphatidic acid controls endosomal cholesterol levels. J Biol Chem 283:27871-27880.
5. Davidson CD, Ali NF, Micsenyi MC, Stephney G, Renault S, Dobrenis K, Ory DS, Vanier MT, Walkley SU (2009) Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates neuronal cholesterol and glycosphingolipid storage and disease progression. PLoS One 4:e6951.
6. Dietschy JM (2009) Central nervous system: cholesterol turnover, brain development and neurodegeneration. Biol Chem 390:287-293.
7. Dietschy JM, Turley SD (2004) Cholesterol metabolism in the central ner-vous system during early development and in the mature animal. J Lipid Res 45:1375-1397.
8. Dietschy JM, Turley SD, Spady DK (1993) Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans. J Lipid Res 34:1637-1659.
9. Du H, Cameron TL, Garger SJ, Pogue GP, Hamm LA, White E, Hanley KM, Grabowski GA (2008) Wolman disease/cholesteryl ester storage disease: efficacy of plant-produced human lysosomal acid lipase in mice. J Lipid Res 49:1646-1657.
10. German DC, Quintero EM, Liang CL, Ng B, Punia S, Xie C, Dietschy JM (2001) Selective neurodegeneration, without neurofibrillary tangles, in a mouse model of Niemann-Pick C disease. J Comp Neurol 433:415-425.
11. Goldman SD, Krise JP (2010) Niemann-Pick C1 functions independently of Niemann-Pick C2 in the initial stage of retrograde transport of membrane-impermeable lysosomal cargo. J Biol Chem 285:4983-4994.
12. Gondré-Lewis MC, McGlynn R, Walkley SU (2003) Cholesterol accumulation in NPC1-deficient neurons is ganglioside dependent. Curr Biol 13:1324-1329.
13. Hayashi H, Campenot RB, Vance DE, Vance JE (2004) Glial lipoproteins stimulate axon growth of central nervous system neurons in compartmented cultures. J Biol Chem 279:14009-14015.
14. Johanson CE, Duncan JA, Klinge PM, Brinker T, Stopa EG, Silverberg GD (2008) Multiplicity of cerebrospinal fluid functions: New challenges in health and disease. Cerebrospinal Fluid Res 5:10.
15. Karten B, Vance DE, Campenot RB, Vance JE (2002) Cholesterol accumulates in cell bodies, but is decreased in distal axons, of Niemann-Pick C1-deficient neurons. J Neurochem 83:1154-1163.
16. Karten B, Hayashi H, Francis GA, Campenot RB, Vance DE, Vance JE (2005) Generation and function of astroglial lipoproteins from Niemann-Pick type C1-deficient mice. Biochem J 387:779-788.
17. Kurrasch DM, Huang J, Wilkie TM, Repa JJ (2004) Quantitative real-time polymerase chain reaction measurement of regulators of G-protein signaling mRNA levels in mouse tissues. Methods Enzymol 389:3-15.
18. Li H, Repa JJ, Valasek MA, Beltroy EP, Turley SD, German DC, Dietschy JM (2005) Molecular, anatomical, and biochemical events associated with neurodegeneration in mice with Niemann-Pick type C disease. J Neuropathol Exp Neurol 64:323-333.
19. Li H, Turley SD, Liu B, Repa JJ, Dietschy JM (2008) GM2/GD2 and GM3 gangliosides have no effect on cellular cholesterol pools or turnover in normal or NPC1 mice. J Lipid Res 49:1816-1828.
20. Liu B, Xie C, Richardson JA, Turley SD, Dietschy JM (2007) Receptormediated and bulk-phase endocytosis cause macrophage and cholesterol accumulation in Niemann-Pick C disease. J Lipid Res 48:1710-1723.
21. Liu B, Li H, Repa JJ, Turley SD, Dietschy JM (2008) Genetic variations and treatments that affect the lifespan of the NPC1 mouse. J Lipid Res 49:663-669.
22. Liu B, Turley SD, Burns DK, Miller AM, Repa JJ, Dietschy JM (2009) Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1+/+ mouse. Proc Natl Acad Sci U S A 106:2377-2382.
23. Liu B, Ramirez CM, Miller AM, Repa JJ, Turley SD, Dietschy JM (2010) Cyclodextrin overcomes the transport defect in nearly every organ of NPC1 mice leading to excretion of sequestered cholesterol as bile acid. J Lipid Res 51:933-944.
24. Loftus SK, Morris JA, Carstea ED, Gu JZ, Cummings C, Brown A, Ellison J, Ohno K, Rosenfeld MA, Tagle DA, Pentchev PG, Pavan WJ (1997) Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene. Science 277:232-235.
25. Lütjohann D, Breuer O, Ahlborg G, Nennesmo I, Sidén Å, Diczfalusy U, Björkhem I (1996) Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation. Proc Natl Acad Sci U S A 93:9799-9804.
26. Mauch DH, Nägler K, Schumacher S, Göritz C, Müller EC, Otto A, Pfrieger FW (2001) CNS synaptogenesis promoted by glia-derived cholesterol. Science 294:1354-1357.
27. Möbius W, van Donselaar E, Ohno-Iwashita Y, Shimada Y, Heijnen HF, Slot JW, Geuze HJ (2003) Recycling compartments and the internal vesicles of multivesicular bodies harbor most of the cholesterol found in the endocytic pathway. Traffic 4:222-231.
28. Neufeld EB, Wastney M, Patel S, Suresh S, Cooney AM, Dwyer NK, Roff CF, Ohno K, Morris JA, Carstea ED, Incardona JP, Strauss JF 3rd, Vanier MT, Patterson MC, Brady RO, Pentchev PG, Blanchette-Mackie EJ (1999) The Niemann-Pick C1 protein resides in a vesicular compartment linked to retrograde transport of multiple lysosomal cargo. J Biol Chem 274:9627-9635.
29. Nieweg K, Schaller H, Pfrieger FW (2009) Marked differences in cholesterol synthesis between neurons and glial cells from postnatal rats. J Neurochem 109:125-134.
30. Pfrieger FW (2003) Cholesterol homeostasis and function in neurons of the central nervous system. Cell Mol Life Sci 60:1158-1171.
31. Pieper AA, Wu X, Han TW, Estill SJ, Dang Q, Wu LC, Reece-Fincanon S, Dudley CA, Richardson JA, Brat DJ, McKnight SL (2005) The neuronal PAS domain protein 3 transcription factor controls FGF-mediated adult hippocampal neurogenesis in mice. Proc Natl Acad Sci U S A 102:14052-14057.
32. Posse De Chaves EI, Vance DE, Campenot RB, Kiss RS, Vance JE (2000) Uptake of lipoproteins for axonal growth of sympathetic neurons. J Biol Chem 275:19883-19890.
33. Quan G, Xie C, Dietschy JM, Turley SD (2003) Ontogenesis and regulation of cholesterol metabolism in the central nervous system of the mouse. Brain Res Dev Brain Res 146:87-98.
34. Ramirez CM, Liu B, Taylor AM, Repa JJ, Burns DK, Weinberg AG, Turley SD, Dietschy JM (2010) Weekly cyclodextrin administration normalizes cholesterol metabolism in nearly every organ of the Niemann-Pick type C1 mouse and markedly prolongs life. Pediatr Res 68:309-315.
35. Ramirez CM, Liu B, Aqul A, Taylor AM, Repa JJ, Turley SD, Dietschy JM (2011) Quantitative role of LAL, NPC2, and NPC1 in lysosomal cholesterol processing defined by genetic and pharmacological manipulations. J Lipid Res 52:688-698.
36. Repa JJ, Turley SD, Quan G, Dietschy JM (2005) Delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorption. J Lipid Res 46:779-789.
37. Repa JJ, Li H, Frank-Cannon TC, Valasek MA, Turley SD, Tansey MG, Dietschy JM (2007) Liver X receptor activation enhances cholesterol loss from the brain, decreases neuroinflammation, and increases survival of the NPC1 mouse. J Neurosci 27:14470-14480.
38. Rosenbaum AI, Zhang G, Warren JD, Maxfield FR (2010) Endocytosis of beta-cyclodextrins is responsible for cholesterol reduction in Niemann-Pick type C mutant cells. Proc Natl Acad Sci U S A 107:5477-5482.
39. Syková E, Nicholson C (2008) Diffusion in brain extracellular space. Physiol Rev 88:1277-1340.
40. Thorne RG, Lakkaraju A, Rodriguez-Boulan E, Nicholson C (2008) In vivo diffusion of lactoferrin in brain extracellular space is regulated by interactions with heparan sulfate. Proc Natl Acad Sci U S A 105:8416-8421.
41. Xie C, Lund EG, Turley SD, Russell DW, Dietschy JM (2003) Quantitation of two pathways for cholesterol excretion from the brain in normal mice and mice with neurodegeneration. J Lipid Res 44:1780-1789.