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파킨슨병의 원인유전자와 연관된 자가포식현상

The Role of Autophagy Associated With Causative Genes Parkinson’s Disease

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초록

Parkinson’s disease (PD) is the second most common neurodegenerative motor disorder, affecting approximately 1 % ofthe population aged ≥60 years. Recent investigations have shown that in addition to motor symptoms such asbradykinesia, resting tremor, and gait instability, PD also causes non-motor symptoms such as insomnia, constipation,depression, and dementia. Most PD cases occurred sporadically, but 5-10% is inherited as familial PD, and severalPD-causative genes have been identified and intensively studied. Autophagy is a self-degrading mechanism of balancingthe energy source in response to nutrient shortage and various stresses, and is a tightly regulated and complicatedprocess that generates double-membrane organelles. Autophagy failure has recently been observed in both animal PDmodels and human PD patients. The intention of this review is to introduce recent findings regarding the relationshipbetween causative genetic mutations in PD and autophagy, from a clinical perspective.

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative motor disorder, affecting approximately 1 % ofthe population aged ≥60 years. Recent investigations have shown that in addition to motor symptoms such asbradykinesia, resting tremor, and gait instability, PD also causes non-motor symptoms such as insomnia, constipation,depression, and dementia. Most PD cases occurred sporadically, but 5-10% is inherited as familial PD, and severalPD-causative genes have been identified and intensively studied. Autophagy is a self-degrading mechanism of balancingthe energy source in response to nutrient shortage and various stresses, and is a tightly regulated and complicatedprocess that generates double-membrane organelles. Autophagy failure has recently been observed in both animal PDmodels and human PD patients. The intention of this review is to introduce recent findings regarding the relationshipbetween causative genetic mutations in PD and autophagy, from a clinical perspective.

참고문헌 (53)

  1. Van Den Eeden SK, "Incidence of Parkinson's disease: variation by age, gender, and race", ethnicity, 2003, pp.157, 1015~1022
  2. de Rijk MC, "Prevalence of Parkinson's disease in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group", Neurology, 54, pp.S21~S23 (2000)
  3. Dauer W, "Parkinson's disease: mechanisms and models", Neuron, 39, pp.889~909 (2003)
  4. Sellbach AN, "Parkinson's disease and family history", Parkinsonism Relat Disord, 12, pp.399~409 (2006)
  5. Bekris LM, "The Genetics of Parkinson Disease", J Geriatr Psychiatry Neurol, 23, pp.228~242 (2011)
  6. Braak H, "Staging of brain pathology related to sporadic Parkinson's disease", Neurobiol Aging, 24, pp.197~211 (2003)
  7. Desplats P, "Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein", Proc Natl Acad Sci U S A, 106, pp.13010~13015 (2009)
  8. Danzer KM, "Exosomal cell-to-cell transmission of alpha synuclein oligomers", Mol Neurodegener, 7, pp.42~ (2012)
  9. Lynch-Day MA, "The role of autophagy in Parkinson's disease", Cold Spring Harb Perspect Med, 2, pp.a009357~ (2012)
  10. Cheung ZH, "The emerging role of autophagy in Parkinson's disease", Mol Brain, 2, pp.29~ (2009)
  11. Dupont N, "Shigella phagocytic vacuolar membrane remnants participate in the cellular response to pathogen invasion and are regulated by autophagy", Cell Host Microbe, 6, pp.137~149 (2009)
  12. Zheng YT, "The adaptor protein p62", SQSTM1 targets invading bacteria to the autophagy pathway, 2009, pp.183, 5909~5916
  13. Klionsky DJ, "A comprehensive glossary of autophagy-related molecules and processes (2nd edition)", Autophagy, 7, pp.1273~1294 (2011)
  14. de Vries RL, "Mitophagy and Parkinson's disease: be eaten to stay healthy", Mol Cell Neurosci, 55, pp.37~43 (2013)
  15. Ohsumi, Y, "Molecular dissection of autophagy: two ubiquitin-like systems", Nat Rev Mol Cell Biol, 2, pp.211~216 (2001)
  16. He C, "Regulation mechanisms and signaling pathways of autophagy", Annu Rev Genet, 43, pp.67~93 (2009)
  17. Polymeropoulos MH, "Mutation in the alpha-synuclein gene identified in families with Parkinson's disease", Science, 276, pp.2045~2047 (1997)
  18. Gasser T, "Update on the genetics of Parkinson's disease", Mov Disord, 22(Suppl 17), pp.S343~S350 (2007)
  19. Klein C, "The genetics of Parkinson disease:Implications for neurological care", Nat Clin Pract Neurol, 2, pp.136~146 (2006)
  20. Ibanez P, "Causal relation between alpha-synuclein gene duplication and familial Parkinson's disease", Lancet, 364, pp.1169~1171 (2004)
  21. Martinez-Vicente M, "Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy", J Clin Invest, 118, pp.777~788 (2008)
  22. Winslow AR, "Alpha-Synuclein impairs macroautophagy: implications for Parkinson's disease", J Cell Biol, 190, pp.1023~1037 (2010)
  23. Choubey V, "Mutant A53T alpha-synuclein induces neuronal death by increasing mitochondrial autophagy", J Biol Chem, 286, pp.10814~10824 (2011)
  24. Zimprich A, "Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology", Neuron, 44, pp.601~607 (2004)
  25. Zhang J, "Characterization of TAE684 as a potent LRRK2 kinase inhibitor", Bioorg Med Chem Lett, 22, pp.1864~1869 (2012)
  26. Reith AD, "GSK2578215A; a potent and highly selective 2-arylmethyloxy-5-substitutent-N-arylbenzamide LRRK2 kinase inhibitor", Bioorg Med Chem Lett, 22, pp.5625~5629 (2012)
  27. Yun H, "Identification of chemicals to inhibit the kinase activity of leucine-rich repeat kinase 2(LRRK2), a Parkinson's disease-associated protein", Bioorg Med Chem Lett, 21, pp.2953~2957 (2011)
  28. Kim JS, "A Korean Parkinson's disease family with the LRRK2 p.Tyr1699Cys mutation showing clinical heterogeneity", Mov Disord, 27, pp.320~324 (2012)
  29. Gomez-Suaga P, "LRRK2 as a modulator of lysosomal calcium homeostasis with downstream effects on autophagy", Autophagy, 8, pp.692~693 (2012)
  30. Gomez-Suaga P, "A link between LRRK2, autophagy and NAADP-mediated endolysosomal calcium signalling", Biochem Soc Trans, 40, pp.1140~1146 (2012)
  31. Alegre-Abarrategui J, "LRRK2 regulates autophagic activity and localises to specific membrane microdomains in a novel human genomic reporter cellular model", Hum Mol Genet, 18, pp.4022~4033 (2009)
  32. Gomez-Suaga P, "A Link between Autophagy and the Pathophysiology of LRRK2 in Parkinson's Disease", Parkinsons Dis, 2012, pp.324521~ (2012)
  33. Gomez-Suaga P, "Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP", Hum Mol Genet, 21, pp.511~525 (2012)
  34. MacLeod D, "The familial Parkinsonism gene LRRK2 regulates neurite process morphology", Neuron, 52, pp.587~593 (2006)
  35. Orenstein SJ, "Interplay of LRRK2 with chaperone-mediated autophagy", Nat Neurosci, 16, pp.394~406 (2013)
  36. Jin SM, "Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL", J Cell Biol, 191, pp.933~942 (2010)
  37. Geisler S, "The PINK1", Parkin-mediated mitophagy is compromised by PD-associated mutations, 2010, pp.6, 871~878
  38. Kondapalli C, "PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65", Open Biol, 2, pp.120080~ (2012)
  39. Kim Y, "PINK1 controls mitochondrial localization of Parkin through direct phosphorylation", Biochem Biophys Res Commun, 377, pp.975~980 (2008)
  40. Chen Y, "PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria", Science, 340, pp.471~475 (2012)
  41. Terzioglu M, "Parkinson's disease: genetic versus toxin-induced rodent models", Febs J, 275, pp.1384~1391 (2008)
  42. Narendra D, "p62", SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both, 2010, pp.6, 1090~1106
  43. Gegg ME, "PINK1-parkin-dependent mitophagy involves ubiquitination of mitofusins 1 and 2: Implications for Parkinson disease pathogenesis", Autophagy, 7, pp.243~245 (2010)
  44. Kirkin V, "A role for ubiquitin in selective autophagy", Mol Cell, 34, pp.259~269 (2009)
  45. Chan NC, "Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy", Hum Mol Genet, 20, pp.1726~1737 (2011)
  46. Burchell VS, "The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy", Nat Neurosci, 16, pp.1257~1265 (2013)
  47. Krebiehl G, "Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson's disease-associated protein DJ-1", PLoS One, 5, pp.e9367~ (2010)
  48. Dehay B, "Lysosomal dysfunction in Parkinson disease: ATP13A2 gets into the groove", Autophagy, 8, pp.1389~1391 (2012)
  49. Beilina A, "Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease", Proc Natl Acad Sci U S A, 111, pp.2626~2631 (2014)
  50. Oueslati A, "Polo-like kinase 2regulates selective autophagic alpha-synuclein clearance and suppresses its toxicity in vivo", Proc Natl Acad Sci U S A, 110, pp.E3945~E3954 (2013)
  51. Van Humbeeck C, "Parkin interacts with Ambra1 to induce mitophagy", J Neurosci, 31, pp.10249~10261 (2011)
  52. Michiorri, S, "The Parkinson-associated protein PINK1 interacts with Beclin1 and promotes autophagy", Cell Death Differ, 17, pp.962~974 (2010)
  53. Anglade P, "Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease", Histol Histopathol, 12, pp.25~31 (1997)

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