Mechanizmy neurodegeneracji i jej markery w stwardnieniu rozsianym

• Authors: Paweł Woliński , Marcin Jałosiński , Andrzej Głąbiński

Title variants

EN

Mechanisms of neurodegeneration and its markers in multiple sclerosis

• Languages of publication: EN PL

Abstracts

EN

Neurodegeneration is a very important process in the pathology of multiple sclerosis (MS). However, mechanisms leading to neurodegeneration in MS are still poorly understood. One of the most probable mechanisms triggering damage of the neuron is apoptosis induced by calcium-dependent enzymes. This review presents the mechanism of calcium overload of neuronal cell and also describes the direct and indirect mechanisms of neurodegeneration. Direct mechanism of neurodegeneration is induced by infiltration of the central nervous system (CNS) by immune cells like T-cells and macrophages and their direct damaging interactions with neurons. Many particular molecules like TRAIL, CD95, TNF-α, TNF-β on immune cells, and CD95/Fas/Apo-1, TNFR1, TNFR2, DR3/Wd1-1/Tramp, DR4/TRAIL-R1, DR5/TRAIL-R2/TRICK/Killer and DR6 on the CNS cells are involved in this process. The direct mechanism of neurodegeneration may be also induced by ROS (reactive oxygen species) and NO (nitric oxide) produced by macrophages and microglia in inflammatory foci. Indirect, secondary mechanism of neurodegeneration is mainly induced by primary demyelination. Furthermore, this paper describes in details the current knowledge about the possible markers of neurodegeneration in MS like neurofilaments; anti-neurofilaments antibodies; tubulin, actin and anti-tubulin, anti-actin antibodies; tau i fosfo-tau proteins; 24S-hydroxycholesterol (24S-ChOH); apolipoprotein E (ApoE); amyloid precursor protein (APP); N-acetylaspartate (NAA); 14-3-3 protein; neuron-specific enolase (NSE); and S100B (S100 calcium binding protein B).

PL

Zjawisko neurodegeneracji (utraty neuronów) jest bardzo ważnym procesem w patologii stwardnienia rozsianego (sclerosis multiplex, SM). Mechanizmy prowadzące do uszkodzenia neuronów w ośrodkowym układzie nerwowym (OUN) w chorobach demielinizacyjnych i neurodegeneracyjnych nie zostały jak dotąd ostatecznie wyjaśnione. Jednym z najbardziej prawdopodobnych mechanizmów prowadzących do uszkodzenia komórek nerwowych jest proces apoptozy wywołany przez enzymy zależne od jonów Ca2+. W niniejszej pracy opisano prawdopodobny mechanizm prowadzący do akumulacji w komórce nerwowej jonów wapnia, a także drogę bezpośredniej i pośredniej neurodegeneracji. Droga bezpośrednia polega na uszkodzeniu neuronów przez kontaktujące się z nimi limfocyty T oraz monocyty infiltrujące ośrodkowy układ nerwowy (OUN). W procesie tym zaangażowanych jest wiele specyficznych molekuł zlokalizowanych na komórkach zapalnych (TRAIL, cD95, TNF-α, TNF-β), a także na komórkach OUN, w tym na neuronach (CD95/Fas/Apo-1, TNFR1, TNFR2, DR3/Wd1-1/Tramp, DR4/TRAIL-R1, DR5/TRAIL-R2/TRICK/Killer oraz DR6). Neuro-degeneracja bezpośrednia może też być wywołana przez reaktywne formy tlenu i tlenek azotu wydzielane przez makrofagi i mikroglej w ogniskach zapalnych. Do procesu neurodegeneracji może dochodzić również na drodze pośredniej, wtórnej względem demielinizacji, która jest konsekwencją procesu zapalnego. Oprócz tego szczegółowo przedstawiono aktualną wiedzę na temat takich markerów neurodegeneracji w SM, jak neuro-filamenty, przeciwciała przeciwko neurofilamentom, tubulina, aktyna i przeciwciała anty-tubulina i anty-akty-na, białko tau i fosfo-tau, 24S-hydroksycholesterol (24S-ChOH), apolipoproteina E (ApoE), białko prekurso-rowe amyloidu (APP), kwas N-acetyloasparaginowy (NAA), białko 14-3-3, specyficzna enolaza neuronalna (NSE) oraz białko S100B.

Keywords

EN

atrofia mózgu; brain atrophy; markery neurodegeneracji; multiple sclerosis; neurodegeneracja; neurodegeneration; neurodegeneration markers; neuronal loss; stwardnienie rozsiane; utrata neuronów

Discipline

• MEDICINE: MEDICINE

• Publisher: Medical Communications
• Journal: Aktualności Neurologiczne
• Year: 2008
• Volume: 8
• Issue: 1
• Pages: 25-32

Contributors

author

Paweł Woliński

• Klinika Neurologii i Epileptologii z Oddziałem Udarowym, Uniwersytet Medyczny w Łodzi. Oddział Kliniczny Propedeutyki Neurologicznej z Pododdziałem Udarowym, Uniwersytet Medyczny w Łodzi

author

Marcin Jałosiński

• Klinika Neurologii i Epileptologii z Oddziałem Udarowym, Uniwersytet Medyczny w Łodzi

author

Andrzej Głąbiński

• Klinika Neurologii i Epileptologii z Oddziałem Udarowym, Uniwersytet Medyczny w Łodzi. Oddział Kliniczny Propedeutyki Neurologicznej z Pododdziałem Udarowym, Uniwersytet Medyczny w Łodzi.

References

• 1. Peruzzi F., Bergonzini V, Aprea S. i wsp.: Cross talk between growth factors and viral and cellular factors alters neuronal signaling pathways: implication for HIV-associated dementia. Brain Res. Brain Res. Rev. 2005; 50: 114-125.
• 2. DeLuca G.C., Ebers G.C., Esiri M.M.: Axonal loss in multiple sclerosis: a pathological survey of the corticospinal and sensory tracts. Brain 2004; 127: 1009-1018.
• 3. Yuan J., Yankner B.A.: Apoptosis in the nervous system. Nature 2000; 407: 802-809.
• 4. Trapp B.D., Peterson J., Ransohoff R.M. i wsp.: Axonal transection in the lesions of multiple sclerosis. N. Engl. J. Med. 1998; 338: 278-285.
• 5. Charcot M.: Histology of sclerotic plaques. Gazette Hopitaux 1868; 141: 554-558.
• 6. Trapp B.D., Bo L., Mork S., Chang A.: Pathogenesis of tissue injury in MS lesions. J. Neuroimmunol. 1999; 98: 49-56.
• 7. Justicia C., Ramos-Cabrer P., Hoehn M.: MRI detection of secondary damage after stroke: chronic iron accumulation in the thalamus of the rat brain. Stroke 2008; 39: 1541-1547.
• 8. Tian C., Erdmann N., Zhao J. i wsp.: HIV-infected macrophages mediate neuronal apoptosis through mitochondrial glutaminase. J. Neurochem. 2008; 105: 994-1005.
• 9. Stys P.K.: General mechanisms of axonal damage and its prevention. J. Neurol. Sci. 2005; 233: 3-13.
• 10. Lappe-Siefke C., Goebbels S., Gravel M. i wsp.: Disruption of Cnpl uncouples oligodendroglial functions in axonal support and myelination. Nat. Genet. 2003; 33: 366-374.
• 11. Smith K.J., Lassmann H.: The role of nitric oxide in multiple sclerosis. Lancet Neurol. 2002; 1: 232-241.
• 12. Brown G.C., Borutaite V: Nitric oxide inhibition of mitochondrial respiration and its role in cell death. Free Radic. Biol. Med. 2002; 33: 1440-1450.
• 13. Taylor C.P.: Na+ currents that fail to inactivate. Trends Neurosci. 1993; 16: 455-460.
• 14. Stys P.K., Sontheimer H., Ransom B.R., Waxman S.G.: Noninactivating, tetrodotoxin-sensitive Na+ conductance in rat optic nerve axons. Proc. Natl Acad. Sci. USA 1993: 90: 6976-6980.
• 15. Poliak S., Peles E.: The local differentiation of myelinated axons at nodes of Ranvier. Nat. Rev. Neurosci. 2003; 4: 968-980.
• 16. Stys P.K.: Axonal degeneration in multiple sclerosis: is it time for neuroprotective strategies? Ann. Neurol. 2004; 55: 601-603.
• 17. Waxman S.G., Ritchie J.M.: Molecular dissection of the myelinated axon. Ann. Neurol. 1993; 33: 121-136.
• 18. Nitsch R., Pohl E.E., Smorodchenko A. i wsp.: Direct impact of T cells on neurons revealed by two-photon microscopy in living brain tissue. J. Neurosci. 2004; 24: 2458-2464.
• 19. Aktas O., Smorodchenko A., Brocke S. i wsp.: Neuronal damage in autoimmune neuroinflammation mediated by the death ligand TRAIL. Neuron 2005; 46: 421-432.
• 20. Degterev A., Boyce M., Yuan J.: A decade of caspases. Oncogene 2003; 22: 8543-8567.
• 21. Aktas O., Prozorovski T., Zipp F.: Death ligands and autoimmune demyelination. Neuroscientist 2006; 12: 305-316.
• 22. Traugott U., Reinherz E.L., Raine C.S.: Multiple sclerosis. Distribution of T cells, T cell subsets and Ia-positive macrophages in lesions of different ages. J. Neuroimmunol. 1983; 4: 201-221.
• 23. ChaoC.C., Hu S., EhrlichL., Peterson P.K.: Interleukin-1 and tumor necrosis factor-α synergistically mediate neurotoxicity: involvement of nitric oxide and of N-methyl-D-aspartate receptors. Brain Behav. Immun. 1995; 9: 355-365.
• 24. Chao C.C., Hu S., Sheng WS. i wsp.: Cytokine-stimulated astrocytes damage human neurons via a nitric oxide mechanism. Glia 1996; 16: 276-284.
• 25. He B.P., Wen W, Strong M.J.: Activated microglia (BV-2) facilitation of TNF-a-mediated motor neuron death in vitro. J. Neuroimmunol. 2002; 128: 31-38.
• 26. Bagasra O., Michaels F.H., Zheng Y.M. i wsp.: Activation of the inducible form of nitric oxide synthase in the brains of patients with multiple sclerosis. Proc. Natl Acad. Sci. USA 1995; 92: 12041-12045.
• 27. Ruuls S.R., Bauer J., Sontrop K. i wsp.: Reactive oxygen species are involved in the pathogenesis of experimental allergic encephalomyelitis in Lewis rats. J. Neuroimmunol. 1995; 56: 207-217.
• 28. Lu F., Selak M., O’Connor J. i wsp.: Oxidative damage to mitochondrial DNA and activity of mitochondrial enzymes in chronic active lesions of multiple sclerosis. J. Neurol. Sci. 2000; 177: 95-103.
• 29. Vladimirova O., Lu F.M., Shawver L., Kalman B.: The activation of protein kinase C induces higher production of reactive oxygen species by mononuclear cells in patients with multiple sclerosis than in controls. Inflamm. Res. 1999; 48: 412-416.
• 30. Glabinski A., Tawsek N.S., Bartosz G.: Increased generation of superoxide radicals in the blood of MS patients. Acta Neurol. Scand. 1993; 88: 174-177.
• 31. MacMicking J.D., Willenborg D.O., Weidemann M.J. i wsp.: Elevated secretion of reactive nitrogen and oxygen intermediates by inflammatory leukocytes in hyperacute experimental autoimmune encephalomyelitis: enhancement by the soluble products of encephalitogenic T cells. J. Exp. Med. 1992; 176: 303-307.
• 32. Marracci G.H., McKeon G.P., Marquardt W.E. i wsp.: α lipoic acid inhibits human T-cell migration: implications for multiple sclerosis. J. Neurosci. Res. 2004; 78: 362-370.
• 33. Liu Y., Zhu B., Wang X. i wsp.: Bilirubin as a potent antioxidant suppresses experimental autoimmune encephalomyelitis: implications for the role of oxidative stress in the development of multiple sclerosis. J. Neuroimmunol. 2003; 139: 27-35.
• 34. Penkowa M., Hidalgo J.: Treatment with metallothionein prevents demyelination and axonal damage and increases oligodendrocyte precursors and tissue repair during experimental autoimmune encephalomyelitis. J. Neurosci. Res. 2003; 72: 574-586.
• 35. Spitsin S.V, Scott G.S., Mikheeva T. i wsp.: Comparison of uric acid and ascorbic acid in protection against EAE. Free Radic. Biol. Med. 2002; 33: 1363-1371.
• 36. Emerson M.R., LeVine S.M.: Heme oxygenase-1 and NADPH cytochrome P450 reductase expression in experimental allergic encephalomyelitis: an expanded view of the stress response. J. Neurochem. 2000; 75: 2555-2562.
• 37. Choi D.W., Koh J.Y., Peters S.: Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists. J. Neurosci. 1988; 8: 185-196.
• 38. Li S., Stys P.K.: Mechanisms of ionotropic glutamate receptor-mediated excitotoxicity in isolated spinal cord white matter. J. Neurosci. 2000; 20: 1190-1198.
• 39. Holt W.F.: Glutamate in health and disease: the role of inhibitors. W: Bar PR., Beal M.F. (red.): Neuroprotection in CNS Diseases. Marcel Dekker, New York 1997: 87-119.
• 40. Bruck W, Stadelmann C.: The spectrum of multiple sclerosis: new lessons from pathology. Curr. Opin. Neurol. 2005; 18: 221-224.
• 41. Kornek B., Storch M.K., Bauer J. i wsp.: Distribution of a calcium channel subunit in dystrophic axons in multiple sclerosis and experimental autoimmune encephalomyelitis. Brain 2001; 124: 1114-1124.
• 42. Moll C., Mourre C., Lazdunski M., Ulrich J.: Increase of sodium channels in demyelinated lesions of multiple sclerosis. Brain Res. 1991; 556: 311-316.
• 43. Mancardi G., Hart B., Roccatagliata L. i wsp.: Demyelination and axonal damage in a non-human primate model of multiple sclerosis. J. Neurol. Sci. 2001; 184: 41-49.
• 44. Kornek B., Storch M.K., Weissert R. i wsp.: Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am. J. Pathol. 2000; 157: 267-276.
• 45. Lycke J.N., Karlsson J.E., Andersen O., Rosengren L.E.: Neurofilament protein in cerebrospinal fluid: a potential marker of activity in multiple sclerosis. J. Neurol. Neuro-surg. Psychiatry 1998; 64: 402-404.
• 46. Norgren N., Rosengren L., Stigbrand T: Elevated neurofilament levels in neurological diseases. Brain Res. 2003; 987:25-31.
• 47. Eikelenboom M.J., Petzold A., Lazeron R.H. i wsp.: Multiple sclerosis: neurofilament light chain antibodies are correlated to cerebral atrophy. Neurology 2003; 60: 219-223.
• 48. Spillantini M.G., Murrell J.R., Goedert M. i wsp.: Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc. Natl Acad. Sci. USA 1998; 95: 7737-7741.
• 49. Martinez-Yelamos A., Saiz A., Bas J. i wsp.: Tau protein in cerebrospinal fluid: a possible marker of poor outcome in patients with early relapsing-remitting multiple sclerosis. Neurosci. Lett. 2004; 363: 14-17.
• 50. Belting M., Petersson P.: Protective role for proteoglycans against cationic lipid cytotoxicity allowing optimal transfection efficiency in vitro. Biochem. J. 1999; 342: 281-286.
• 51. Leoni V, Masterman T., Diczfalusy U. i wsp.: Changes in human plasma levels of the brain specific oxysterol 24S-hydroxycholesterol during progression of multiple sclerosis. Neurosci. Lett. 2002; 331: 163-166.
• 52. Teunissen C.E., Dijkstra C.D., Polman C.H. i wsp.: Decreased levels of the brain specific 24S-hydroxycholesterol and cholesterol precursors in serum of multiple sclerosis patients. Neurosci. Lett. 2003; 347: 159-162.
• 53. Reiber H.: Dynamics of brain-derived proteins in cerebrospinal fluid. Clin. Chim. Acta 2001; 310: 173-186.
• 54. Mauch D.H., Nagler K., Schumacher S. i wsp.: CNS synaptogenesis promoted by gliaderived cholesterol. Science 2001; 294: 1354-1357.
• 55. Lynch J.R., Tang W., Wang H. i wsp.: APOE genotype and an ApoE-mimetic peptide modify the systemic and central nervous system inflammatory response. J. Biol. Chem. 2003; 278: 48529-48533.
• 56. Brooks J.B., Kasin J.V, Fast D.M., Daneshvar M.I.: Detection of metabolites by frequency-pulsed electron capture gas-liquid chromatography in serum and cerebrospinal fluid of a patient with Nocardia infection. J. Clin. Microbiol. 1987; 25: 445-448.
• 57. Gaillard O., Gervais A., Meillet D. i wsp.: Apolipoprotein E and multiple sclerosis: a biochemical and genetic investigation. J. Neurol. Sci. 1998; 158: 180-186.
• 58. Gelman B.B., Rifai N., Christenson R.H., Silverman L.M.: Cerebrospinal fluid and plasma apolipoproteins in patients with multiple sclerosis. Ann. Clin. Lab. Sci. 1988; 18:46-52.
• 59. Turner PR., O’Connor K., Tate W.P, Abraham W.C.: Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Prog. Neurobiol. 2003; 70: 1-32.
• 60. Ferguson B., Matyszak M.K., Esiri M.M., Perry VH.: Axonal damage in acute multiple sclerosis lesions. Brain 1997; 120: 393-399.
• 61. Stefano G.B., Cadet P, Rialas C.M. i wsp.: Invertebrate opiate immune and neural signaling. Adv. Exp. Med. Biol. 2003; 521: 126-147.
• 62. Berg D., Holzmann C., Riess O.: 14-3-3 proteins in the nervous system. Nat. Rev. Neurosci. 2003; 4: 752-762.
• 63. Satoh J., Yukitake M., Kurohara K. i wsp.: Detection of the 14-3-3 protein in the cerebrospinal fluid of Japanese multiple sclerosis patients presenting with severe myelitis. J. Neurol. Sci. 2003; 212: 11-20.
• 64. Royds J.A., Davies-Jones G.A., Lewtas N.A. i wsp.: Eno-lase isoenzymes in the cerebrospinal fluid of patients with diseases of the nervous system. J. Neurol. Neurosurg. Psychiatry 1983; 46: 1031-1036.
• 65. Missler U., Wandinger K.P, Wiesmann M. i wsp.: Acute exacerbation of multiple sclerosis increases plasma levels of S-100 protein. Acta Neurol. Scand. 1997; 96: 142-144.
• 66. Petzold A., EikelenboomM.J., GvericD. iwsp.: Markers for different glial cell responses in multiple sclerosis: clinical and pathological correlations. Brain 2002; 125:1462-1473.

• Document Type: article