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Journal of Neural Transmission

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01.10.2015 | Neurology and Preclinical Neurological Studies - Review Article

New insights on Parkinson’s disease genes: the link between mitochondria impairment and neuroinflammation

verfasst von: Dorit Trudler, Yuval Nash, Dan Frenkel

Erschienen in: Journal of Neural Transmission | Ausgabe 10/2015

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Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor disturbances, appearance of Lewy bodies and dopaminergic neuronal death. The etiology of PD is unknown, although aging and neurotoxins are established risk factors. The activation of glial cells in the brain is the first defense mechanism against pathological events in neurodegenerative diseases, and neuroinflammation is suggested to play an important role in PD disease progression leading to dopaminergic neuronal degeneration. Gene mutations in several PD-related genes may affect up to 15 % of the PD cases. These gene mutations can cause either loss or gain of function in their respective proteins leading to autosomal recessive and autosomal dominant PD, respectively. Most of the identified genes play a role in mitochondrial activity and integrity, and this was demonstrated mostly in neuronal cells. In this review, we aim to describe the link between PD-related genes, which are involved in mitochondrial function, and deleterious neuroinflammation.

Abou-Sleiman PM, Healy DG, Quinn N, Lees AJ, Wood NW (2003) The role of pathogenic DJ-1 mutations in Parkinson’s disease. Ann Neurol 54:283–286. doi:10.1002/ana.10675 PubMedCrossRef

Abou-Sleiman PM, Muqit MM, Wood NW (2006) Expanding insights of mitochondrial dysfunction in Parkinson’s disease. Nat Rev Neurosci 7:207–219. doi:10.1038/nrn1868 PubMedCrossRef

Akundi RS et al (2011) Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice. PLoS One 6:e16038. doi:10.1371/journal.pone.0016038 PubMedCentralPubMedCrossRef

Alvarez-Erviti L, Couch Y, Richardson J, Cooper JM, Wood MJ (2011) Alpha-synuclein release by neurons activates the inflammatory response in a microglial cell line. Neurosci Res 69:337–342. doi:10.1016/j.neures.2010.12.020 PubMedCrossRef

Bader V, Ran Zhu X, Lubbert H, Stichel CC (2005) Expression of DJ-1 in the adult mouse CNS. Brain Res 1041:102–111. doi:10.1016/j.brainres.2005.02.006 PubMedCrossRef

Bandopadhyay R et al (2004) The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson’s disease. Brain 127:420–430. doi:10.1093/brain/awh054 PubMedCrossRef

Benveniste EN (1992) Inflammatory cytokines within the central nervous system: sources, function, and mechanism of action. Am J Physiol 263:C1–C16PubMed

Berger Z, Smith KA, Lavoie MJ (2010) Membrane localization of LRRK2 is associated with increased formation of the highly active LRRK2 dimer and changes in its phosphorylation. Biochemistry 49:5511–5523. doi:10.1021/bi100157u PubMedCentralPubMedCrossRef

Biskup S et al (2006) Localization of LRRK2 to membranous and vesicular structures in mammalian brain. Ann Neurol 60:557–569. doi:10.1002/ana.21019 PubMedCrossRef

Blackinton J et al (2005) Effects of DJ-1 mutations and polymorphisms on protein stability and subcellular localization. Brain Res Mol Brain Res 134:76–83. doi:10.1016/j.molbrainres.2004.09.004 PubMedCrossRef

Blesa J, Phani S, Jackson-Lewis V, Przedborski S (2012) Classic and new animal models of Parkinson’s disease. J Biomed Biotechnol 2012:845618. doi:10.1155/2012/845618 PubMedCentralPubMedCrossRef

Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8:57–69. doi:10.1038/nrn2038 PubMedCrossRef

Bonifati V et al (2003) Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299:256–259. doi:10.1126/science.1077209 PubMedCrossRef

Brochard V et al (2009) Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Investig 119:182–192. doi:10.1172/JCI36470 PubMedCentralPubMed

Cabezas R, Avila MF, Torrente D, El-Bachá RS, Morales L, Gonzalez J, Barreto GE (2013) Astrocytes role in Parkinson: a double-edged sword. In: Uday Kishore (ed) Neurodegenerative disease. doi:10.5772/54305

Carvey PM, Punati A, Newman MB (2006) Progressive dopamine neuron loss in Parkinson’s disease: the multiple hit hypothesis. Cell Transplant 15:239–250PubMedCrossRef

Casarejos MJ, Menendez J, Solano RM, Rodriguez-Navarro JA, Garcia de Yebenes J, Mena MA (2006) Susceptibility to rotenone is increased in neurons from parkin null mice and is reduced by minocycline. J Neurochem 97:934–946. doi:10.1111/j.1471-4159.2006.03777.x PubMedCrossRef

Castano A, Herrera AJ, Cano J, Machado A (1998) Lipopolysaccharide intranigral injection induces inflammatory reaction and damage in nigrostriatal dopaminergic system. J Neurochem 70:1584–1592PubMedCrossRef

Chen L et al (2005) Age-dependent motor deficits and dopaminergic dysfunction in DJ-1 null mice. J Biol Chem 280:21418–21426. doi:10.1074/jbc.M413955200 PubMedCrossRef

Chen PC, Vargas MR, Pani AK, Smeyne RJ, Johnson DA, Kan YW, Johnson JA (2009) Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson’s disease: critical role for the astrocyte. Proc Natl Acad Sci USA 106:2933–2938. doi:10.1073/pnas.0813361106 PubMedCentralPubMedCrossRef

Chinta SJ, Mallajosyula JK, Rane A, Andersen JK (2010) Mitochondrial alpha-synuclein accumulation impairs complex I function in dopaminergic neurons and results in increased mitophagy in vivo. Neurosci Lett 486:235–239. doi:10.1016/j.neulet.2010.09.061 PubMedCentralPubMedCrossRef

Chung JY et al (2013) Elevated TRAF2/6 expression in Parkinson’s disease is caused by the loss of Parkin E3 ligase activity laboratory investigation. J Tech Methods Pathol. doi:10.1038/labinvest.2013.60

Conway KA, Harper JD, Lansbury PT Jr (2000) Fibrils formed in vitro from alpha-synuclein and two mutant forms linked to Parkinson’s disease are typical amyloid. Biochemistry 39:2552–2563PubMedCrossRef

Cooper O et al (2012) Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson’s disease. Sci Trans Med 4:141ra190. doi:10.1126/scitranslmed.3003985 CrossRef

Croisier E, Moran LB, Dexter DT, Pearce RK, Graeber MB (2005) Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition. J Neuroinflamm 2:14. doi:10.1186/1742-2094-2-14 CrossRef

Dagda RK, Cherra SJ 3rd, Kulich SM, Tandon A, Park D, Chu CT (2009) Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission. J Biol Chem 284:13843–13855. doi:10.1021/bi991447r PubMedCentralPubMedCrossRef

Deas E, Plun-Favreau H, Wood NW (2009) PINK1 function in health and disease. EMBO Mol Med 1:152–165. doi:10.1002/emmm.200900024 PubMedCentralPubMedCrossRef

Deng H, Jankovic J, Guo Y, Xie W, Le W (2005) Small interfering RNA targeting the PINK1 induces apoptosis in dopaminergic cells SH-SY5Y. Biochem Biophys Res Commun 337:1133–1138. doi:10.1016/j.bbrc.2005.09.178 PubMedCrossRef

Dexter DT et al (1989) Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. J Neurochem 52:381–389PubMedCrossRef

Fahn S, Clarence-Smith KE, Chase TN (1998) Parkinson’s disease: neurodegenerative mechanisms and neuroprotective interventions—report of a workshop. Mov Disord 13:759–767. doi:10.1002/mds.870130502 PubMedCrossRef

Frank-Cannon TC et al (2008) Parkin deficiency increases vulnerability to inflammation-related nigral degeneration. J Neurosci 28:10825–10834. doi:10.1523/JNEUROSCI.3001-08.2008 PubMedCentralPubMedCrossRef

Frohman EM et al (2005) Therapeutic considerations for disease progression in multiple sclerosis: evidence, experience, and future expectations. Arch Neurol 62:1519–1530. doi:10.1001/archneur.62.10.1519 PubMed

Gandhi S et al (2006) PINK1 protein in normal human brain and Parkinson’s disease. Brain 129:1720–1731. doi:10.1093/brain/awl114 PubMedCrossRef

Gandhi S et al (2009) PINK1-associated Parkinson’s disease is caused by neuronal vulnerability to calcium-induced cell death. Mol Cell 33:627–638. doi:10.1016/j.molcel.2009.02.013 PubMedCentralPubMedCrossRef

Gao HM, Kotzbauer PT, Uryu K, Leight S, Trojanowski JQ, Lee VM (2008) Neuroinflammation and oxidation/nitration of alpha-synuclein linked to dopaminergic neurodegeneration. J Neurosci 28:7687–7698. doi:10.1523/JNEUROSCI.0143-07.2008 PubMedCentralPubMedCrossRef

Gao HM, Zhang F, Zhou H, Kam W, Wilson B, Hong JS (2011a) Neuroinflammation and alpha-synuclein dysfunction potentiate each other, driving chronic progression of neurodegeneration in a mouse model of Parkinson’s disease. Environ Health Perspect 119:807–814. doi:10.1289/ehp.1003013 PubMedCentralPubMedCrossRef

Gao HM, Zhou H, Zhang F, Wilson BC, Kam W, Hong JS (2011b) HMGB1 acts on microglia Mac1 to mediate chronic neuroinflammation that drives progressive neurodegeneration. J Neurosci 31:1081–1092. doi:10.1523/JNEUROSCI.3732-10.2011 PubMedCentralPubMedCrossRef

Gillardon F, Schmid R, Draheim H (2012) Parkinson’s disease-linked leucine-rich repeat kinase 2(R1441G) mutation increases proinflammatory cytokine release from activated primary microglial cells and resultant neurotoxicity. Neuroscience 208:41–48. doi:10.1016/j.neuroscience.2012.02.001 PubMedCrossRef

Goldberg MS et al (2003) Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J Biol Chem 278:43628–43635. doi:10.1074/jbc.M308947200 PubMedCrossRef

Goldberg MS et al (2005) Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron 45:489–496. doi:10.1016/j.neuron.2005.01.041 PubMedCrossRef

Greene JC, Whitworth AJ, Kuo I, Andrews LA, Feany MB, Pallanck LJ (2003) Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci USA 100:4078–4083. doi:10.1073/pnas.0737556100 PubMedCentralPubMedCrossRef

Gu XL, Long CX, Sun L, Xie C, Lin X, Cai H (2010) Astrocytic expression of Parkinson’s disease-related A53T alpha-synuclein causes neurodegeneration in mice. Mol Brain 3:12. doi:10.1186/1756-6606-3-12 PubMedCentralPubMedCrossRef

Haelterman NA, Yoon WH, Sandoval H, Jaiswal M, Shulman JM, Bellen HJ (2014) A mitocentric view of Parkinson’s disease. Annu Rev Neurosci 37:137–159. doi:10.1146/annurev-neuro-071013-014317 PubMedCrossRefPubMedCentral

Hakimi M et al (2011) Parkinson’s disease-linked LRRK2 is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structures. J Neural Transm 118:795–808. doi:10.1007/s00702-011-0653-2 PubMedCentralPubMedCrossRef

Hayashi T et al (2009) DJ-1 binds to mitochondrial complex I and maintains its activity. Biochem Biophys Res Commun 390:667–672. doi:10.1016/j.bbrc.2009.10.025 PubMedCrossRef

Henchcliffe C, Beal MF (2008) Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis Nature clinical practice. Neurology 4:600–609. doi:10.1038/ncpneuro0924 PubMed

Herrera AJ, Castano A, Venero JL, Cano J, Machado A (2000) The single intranigral injection of LPS as a new model for studying the selective effects of inflammatory reactions on dopaminergic system. Neurobiol Dis 7:429–447. doi:10.1006/nbdi.2000.0289 PubMedCrossRef

Hirsch EC (2000) Glial cells and Parkinson’s disease. J Neurol 247(Suppl 2):II58–II62PubMed

Hirsch EC, Hunot S (2009) Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol 8:382–397. doi:10.1016/S1474-4422(09)70062-6 PubMedCrossRef

Imai Y, Soda M, Takahashi R (2000) Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J Biol Chem 275:35661–35664. doi:10.1074/jbc.C000447200 PubMedCrossRef

Irrcher I et al (2010) Loss of the Parkinson’s disease-linked gene DJ-1 perturbs mitochondrial dynamics. Hum Mol Genet 19:3734–3746. doi:10.1093/hmg/ddq288 PubMedCrossRef

Jenner P (2003) Oxidative stress in Parkinson’s disease. Ann Neurol 53(Suppl 3):S26–S36. doi:10.1002/ana.10483 (discussion S36–S28)PubMedCrossRef

Kamp F et al (2010) Inhibition of mitochondrial fusion by alpha-synuclein is rescued by PINK1, Parkin and DJ-1. EMBO J 29:3571–3589. doi:10.1038/emboj.2010.223 PubMedCentralPubMedCrossRef

Kim RH et al (2005) Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and oxidative stress. Proc Natl Acad Sci USA 102:5215–5220. doi:10.1073/pnas.0501282102 PubMedCentralPubMedCrossRef

Kim B et al (2012) Impaired inflammatory responses in murine Lrrk2-knockdown brain microglia. PLoS One 7:e34693. doi:10.1371/journal.pone.0034693 PubMedCentralPubMedCrossRef

Kim J, Byun JW, Choi I, Kim B, Jeong HK, Jou I, Joe E (2013) PINK1 deficiency enhances inflammatory cytokine release from acutely prepared brain slices. Exp Neurobiol 22:38–44. doi:10.5607/en.2013.22.1.38 PubMedCentralPubMedCrossRef

Kitada T et al (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392:605–608. doi:10.1038/33416 PubMedCrossRef

Klegeris A, Giasson BI, Zhang H, Maguire J, Pelech S, McGeer PL (2006) Alpha-synuclein and its disease-causing mutants induce ICAM-1 and IL-6 in human astrocytes and astrocytoma cells. FASEB J 20:2000–2008. doi:10.1096/fj.06-6183com PubMedCrossRef

Klein C, Westenberger A (2012) Genetics of Parkinson’s disease. Cold Spring Harb Perspect Med 2:a008888. doi:10.1101/cshperspect.a008888 PubMedCentralPubMedCrossRef

Klein C, Lohmann-Hedrich K, Rogaeva E, Schlossmacher MG, Lang AE (2007) Deciphering the role of heterozygous mutations in genes associated with parkinsonism. Lancet Neurol 6:652–662. doi:10.1016/S1474-4422(07)70174-6 PubMedCrossRef

Kohutnicka M, Lewandowska E, Kurkowska-Jastrzebska I, Czlonkowski A, Czlonkowska A (1998) Microglial and astrocytic involvement in a murine model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Immunopharmacology 39:167–180PubMedCrossRef

Koutsilieri E, Scheller C, Grunblatt E, Nara K, Li J, Riederer P (2002) Free radicals in Parkinson’s disease. J Neurol 249(Suppl 2):II1–II5. doi:10.1007/s00415-002-1201-7 PubMedCrossRef

Lagace-Wiens PR, Decorby MR, Baudry PJ, Hoban DJ, Karlowsky JA, Zhanel GG (2008) Differences in antimicrobial susceptibility in Escherichia coli from Canadian intensive care units based on regional and demographic variables. Can J Infect Dis Med Microbiol 19:282–286PubMedCentralPubMed

Lee HJ, Jang SH, Kim H, Yoon JH, Chung KC (2012) PINK1 stimulates interleukin-1beta-mediated inflammatory signaling via the positive regulation of TRAF6 and TAK1. Cell Mol Life Sci 69:3301–3315. doi:10.1007/s00018-012-1004-7 PubMedCrossRef

L’Episcopo F et al (2011) Reactive astrocytes and Wnt/beta-catenin signaling link nigrostriatal injury to repair in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease. Neurobiol Dis 41:508–527. doi:10.1016/j.nbd.2010.10.023 PubMedCentralPubMedCrossRef

Lesage S, Brice A (2009) Parkinson’s disease: from monogenic forms to genetic susceptibility factors. Hum Mol Genet 18:R48–R59. doi:10.1093/hmg/ddp012 PubMedCrossRef

Lev N, Ickowicz D, Melamed E, Offen D (2008) Oxidative insults induce DJ-1 upregulation and redistribution: implications for neuroprotection. Neurotoxicology 29:397–405. doi:10.1016/j.neuro.2008.01.007 PubMedCrossRef

Lev N, Ickowicz D, Barhum Y, Melamed E, Offen D (2009) DJ-1 changes in G93A-SOD1 transgenic mice: implications for oxidative stress in ALS. J Mol Neurosci 38:94–102. doi:10.1007/s12031-008-9138-7 PubMedCrossRef

Lev N, Barhum Y, Ben-Zur T, Melamed E, Steiner I, Offen D (2013) Knocking out DJ-1 attenuates astrocytes neuroprotection against 6-hydroxydopamine toxicity. J Mol Neurosci. doi:10.1007/s12031-013-9984-9 PubMed

Lin X et al (2009) Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson’s-disease-related mutant alpha-synuclein. Neuron 64:807–827. doi:10.1016/j.neuron.2009.11.006 PubMedCentralPubMedCrossRef

Liu W et al (2009) PINK1 defect causes mitochondrial dysfunction, proteasomal deficit and alpha-synuclein aggregation in cell culture models of Parkinson’s disease. PLoS One 4:e4597. doi:10.1371/journal.pone.0004597 PubMedCentralPubMedCrossRef

Luk KC, Kehm V, Carroll J, Zhang B, O’Brien P, Trojanowski JQ, Lee VM (2012) Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338:949–953. doi:10.1126/science.1227157 PubMedCentralPubMedCrossRef

Marongiu R et al (2009) Mutant Pink1 induces mitochondrial dysfunction in a neuronal cell model of Parkinson’s disease by disturbing calcium flux. J Neurochem 108:1561–1574. doi:10.1111/j.1471-4159.2009.05932.x PubMedCentralPubMedCrossRef

Masliah E et al (2011) Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease. PLoS One 6:e19338. doi:10.1371/journal.pone.0019338 PubMedCentralPubMedCrossRef

Mastroeni D et al (2009) Microglial responses to dopamine in a cell culture model of Parkinson’s disease. Neurobiol Aging 30:1805–1817. doi:10.1016/j.neurobiolaging.2008.01.001 PubMedCentralPubMedCrossRef

Mayeux R (2003) Epidemiology of neurodegeneration. Annu Rev Neurosci 26:81–104PubMedCrossRef

McGeer PL, McGeer EG (2008) Glial reactions in Parkinson’s disease. Mov Disord 23:474–483. doi:10.1002/mds.21751 PubMedCrossRef

McGeer PL, Itagaki S, Boyes BE, McGeer EG (1988) Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 38:1285–1291PubMedCrossRef

Meulener M et al (2005) Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson’s disease. Curr Biol 15:1572–1577. doi:10.1016/j.cub.2005.07.064 PubMedCrossRef

Miller DW, Hague SM, Clarimon J, Baptista M, Gwinn-Hardy K, Cookson MR, Singleton AB (2004) Alpha-synuclein in blood and brain from familial Parkinson disease with SNCA locus triplication. Neurology 62:1835–1838PubMedCrossRef

Mitsumoto A, Nakagawa Y (2001) DJ-1 is an indicator for endogenous reactive oxygen species elicited by endotoxin. Free Radical Res 35:885–893CrossRef

Moehle MS et al (2012) LRRK2 inhibition attenuates microglial inflammatory responses. J Neurosci 32:1602–1611. doi:10.1523/JNEUROSCI.5601-11.2012 PubMedCentralPubMedCrossRef

Mogi M, Harada M, Kondo T, Riederer P, Inagaki H, Minami M, Nagatsu T (1994a) Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. Neurosci Lett 180:147–150PubMedCrossRef

Mogi M, Harada M, Riederer P, Narabayashi H, Fujita K, Nagatsu T (1994b) Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett 165:208–210PubMedCrossRef

Moriwaki Y, Kim YJ, Ido Y, Misawa H, Kawashima K, Endo S, Takahashi R (2008) L347P PINK1 mutant that fails to bind to Hsp90/Cdc37 chaperones is rapidly degraded in a proteasome-dependent manner. Neurosci Res 61:43–48. doi:10.1016/j.neures.2008.01.006 PubMedCrossRef

Mortiboys H, Johansen KK, Aasly JO, Bandmann O (2010) Mitochondrial impairment in patients with Parkinson disease with the G2019S mutation in LRRK2. Neurology 75:2017–2020. doi:10.1212/WNL.0b013e3181ff9685 PubMedCrossRef

Nagakubo D, Taira T, Kitaura H, Ikeda M, Tamai K, Iguchi-Ariga SM, Ariga H (1997) DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras. Biochem Biophys Res Commun 231:509–513. doi:10.1006/bbrc.1997.6132 PubMedCrossRef

Narendra D, Tanaka A, Suen DF, Youle RJ (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183:795–803. doi:10.1083/jcb.200809125 PubMedCentralPubMedCrossRef

Narendra DP et al (2010) PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 8:e1000298. doi:10.1371/journal.pbio.1000298 PubMedCentralPubMedCrossRef

Nuytemans K, Theuns J, Cruts M, Van Broeckhoven C (2010) Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update. Hum Mutat 31:763–780. doi:10.1002/humu.21277 PubMedCentralPubMedCrossRef

Ooe H, Taira T, Iguchi-Ariga SM, Ariga H (2005) Induction of reactive oxygen species by bisphenol A and abrogation of bisphenol A-induced cell injury by DJ-1. Toxicol Sci 88:114–126. doi:10.1093/toxsci/kfi278 PubMedCrossRef

Orth M, Schapira AH (2002) Mitochondrial involvement in Parkinson’s disease. Neurochem Int 40:533–541PubMedCrossRef

Palacino JJ et al (2004) Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem 279:18614–18622. doi:10.1074/jbc.M401135200 PubMedCrossRef

Parker WD Jr, Parks JK, Swerdlow RH (2008) Complex I deficiency in Parkinson’s disease frontal cortex. Brain Res 1189:215–218. doi:10.1016/j.brainres.2007.10.061 PubMedCentralPubMedCrossRef

Perry TL, Yong VW (1986) Idiopathic Parkinson’s disease, progressive supranuclear palsy and glutathione metabolism in the substantia nigra of patients. Neurosci Lett 67:269–274PubMedCrossRef

Poole AC, Thomas RE, Andrews LA, McBride HM, Whitworth AJ, Pallanck LJ (2008) The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci USA 105:1638–1643. doi:10.1073/pnas.0709336105 PubMedCentralPubMedCrossRef

Pridgeon JW, Olzmann JA, Chin LS, Li L (2007) PINK1 protects against oxidative stress by phosphorylating mitochondrial chaperone TRAP1. PLoS Biol 5:e172. doi:10.1371/journal.pbio.0050172 PubMedCentralPubMedCrossRef

Reynolds AD et al (2008) Nitrated alpha-synuclein-activated microglial profiling for Parkinson’s disease. J Neurochem 104:1504–1525. doi:10.1111/j.1471-4159.2007.05087.x PubMedCrossRef

Rogers J, Mastroeni D, Leonard B, Joyce J, Grover A (2007) Neuroinflammation in Alzheimer’s disease and Parkinson’s disease: are microglia pathogenic in either disorder? Int Rev Neurobiol 82:235–246. doi:10.1016/S0074-7742(07)82012-5 PubMedCrossRef

Roodveldt C et al (2010) Glial innate immunity generated by non-aggregated alpha-synuclein in mouse: differences between wild-type and Parkinson’s disease-linked mutants. PLoS One 5:e13481. doi:10.1371/journal.pone.0013481 PubMedCentralPubMedCrossRef

Runchel C, Matsuzawa A, Ichijo H (2011) Mitogen-activated protein kinases in mammalian oxidative stress responses. Antioxid Redox Signal 15:205–218. doi:10.1089/ars.2010.3733 PubMedCrossRef

Saijo K et al (2009) A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 137:47–59. doi:10.1016/j.cell.2009.01.038 PubMedCentralPubMedCrossRef

Sanders LH et al (2014) LRRK2 mutations cause mitochondrial DNA damage in iPSC-derived neural cells from Parkinson’s disease patients: reversal by gene correction. Neurobiol Dis 62:381–386. doi:10.1016/j.nbd.2013.10.013 PubMedCrossRef

Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD (1990) Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 54:823–827PubMedCrossRef

Schapira AH, Gu M, Taanman JW, Tabrizi SJ, Seaton T, Cleeter M, Cooper JM (1998) Mitochondria in the etiology and pathogenesis of Parkinson’s disease. Ann Neurol 44:S89–S98PubMedCrossRef

Segev-Amzaleg N, Trudler D, Frenkel D (2013) Preconditioning to mild oxidative stress mediates astroglial neuroprotection in an IL-10-dependent manner. Brain Behav Immun 30:176–185. doi:10.1016/j.bbi.2012.12.016 PubMedCrossRef

Shavali S, Brown-Borg HM, Ebadi M, Porter J (2008) Mitochondrial localization of alpha-synuclein protein in alpha-synuclein overexpressing cells. Neurosci Lett 439:125–128. doi:10.1016/j.neulet.2008.05.005 PubMedCentralPubMedCrossRef

Sherer TB, Betarbet R, Greenamyre JT (2002) Environment, mitochondria, and Parkinson’s disease. Neuroscientist 8:192–197PubMed

Sherer TB, Betarbet R, Kim JH, Greenamyre JT (2003) Selective microglial activation in the rat rotenone model of Parkinson’s disease. Neurosci Lett 341:87–90PubMedCrossRef

Shimura H et al (2000) Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet 25:302–305. doi:10.1038/77060 PubMedCrossRef

Sidhu A, Wersinger C, Moussa CE, Vernier P (2004) The role of alpha-synuclein in both neuroprotection and neurodegeneration. Ann N Y Acad Sci 1035:250–270. doi:10.1196/annals.1332.016 PubMedCrossRef

Singleton AB et al (2003) alpha-Synuclein locus triplication causes Parkinson’s disease. Science 302:841. doi:10.1126/science.1090278 PubMedCrossRef

Singleton AB, Farrer MJ, Bonifati V (2013) The genetics of Parkinson’s disease: progress and therapeutic implications. Mov Disord 28:14–23. doi:10.1002/mds.25249 PubMedCentralPubMedCrossRef

Sofroniew MV (2005) Reactive astrocytes in neural repair and protection. Neuroscientist 11:400–407. doi:10.1177/1073858405278321 PubMedCrossRef

Spillantini MG, Crowther RA, Jakes R, Hasegawa M (1998) Alpha-synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. Proc Natl Acad Sci USA 95:6469–6473PubMedCentralPubMedCrossRef

Subramaniam SR, Vergnes L, Franich NR, Reue K, Chesselet MF (2014) Region specific mitochondrial impairment in mice with widespread overexpression of alpha-synuclein. Neurobiol Dis 70:204–213. doi:10.1016/j.nbd.2014.06.017 PubMedCentralPubMedCrossRef

Taira T, Saito Y, Niki T, Iguchi-Ariga SM, Takahashi K, Ariga H (2004) DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep 5:213–218. doi:10.1038/sj.embor.7400074 PubMedCentralPubMedCrossRef

Thevenet J, Pescini Gobert R, Hooft van Huijsduijnen R, Wiessner C, Sagot YJ (2011) Regulation of LRRK2 expression points to a functional role in human monocyte maturation. PLoS One 6:e21519. doi:10.1371/journal.pone.0021519 PubMedCentralPubMedCrossRef

Thomas B (2009) Parkinson’s disease: from molecular pathways in disease to therapeutic approaches. Antioxid Redox Signal 11:2077PubMedCentralPubMedCrossRef

Todd AM, Staveley BE (2008) Pink1 suppresses alpha-synuclein-induced phenotypes in a Drosophila model of Parkinson’s disease. Genome 51:1040–1046. doi:10.1139/G08-085 PubMedCrossRef

Tran TA, Nguyen AD, Chang J, Goldberg MS, Lee JK, Tansey MG (2011) Lipopolysaccharide and tumor necrosis factor regulate Parkin expression via nuclear factor-kappa B. PLoS One 6:e23660. doi:10.1371/journal.pone.0023660 PubMedCentralPubMedCrossRef

Trudler D, Weinreb O, Mandel SA, Youdim MB, Frenkel D (2014) DJ-1 deficiency triggers microglia sensitivity to dopamine toward a pro-inflammatory phenotype that is attenuated by rasagiline. J Neurochem 129:434–447. doi:10.1111/jnc.12633 PubMedCrossRef

Vafai SB, Mootha VK (2012) Mitochondrial disorders as windows into an ancient organelle. Nature 491:374–383. doi:10.1038/nature11707 PubMedCrossRef

Venderova K et al (2009) Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson’s disease. Hum Mol Genet 18:4390–4404. doi:10.1093/hmg/ddp394 PubMedCrossRef

Vives-Bauza C et al (2010) PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci USA 107:378–383. doi:10.1073/pnas.0911187107 PubMedCentralPubMedCrossRef

von Coelln R et al (2006) Inclusion body formation and neurodegeneration are parkin independent in a mouse model of alpha-synucleinopathy. J Neurosci Off J Soc Neurosci 26:3685–3696. doi:10.1523/JNEUROSCI.0414-06.2006 CrossRef

Waak J et al (2009) Regulation of astrocyte inflammatory responses by the Parkinson’s disease-associated gene DJ-1. FASEB J 23:2478–2489. doi:10.1096/fj.08-125153 PubMedCrossRef

Wang X et al (2012) LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1. Hum Mol Genet 21:1931–1944. doi:10.1093/hmg/dds003 PubMedCentralPubMedCrossRef

Watson MB et al (2012) Regionally-specific microglial activation in young mice over-expressing human wildtype alpha-synuclein. Exp Neurol 237:318–334. doi:10.1016/j.expneurol.2012.06.025 PubMedCentralPubMedCrossRef

Weihofen A, Thomas KJ, Ostaszewski BL, Cookson MR, Selkoe DJ (2009) Pink1 forms a multiprotein complex with Miro and Milton, linking Pink1 function to mitochondrial trafficking. Biochemistry 48:2045–2052. doi:10.1021/bi8019178 PubMedCentralPubMedCrossRef

West AB et al (2005) Parkinson’s disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci USA 102:16842–16847. doi:10.1073/pnas.0507360102 PubMedCentralPubMedCrossRef

Wood-Kaczmar A, Gandhi S, Wood NW (2006) Understanding the molecular causes of Parkinson’s disease. Trends Mol Med 12:521–528. doi:10.1016/j.molmed.2006.09.007 PubMedCrossRef

Xie W, Chung KK (2012) Alpha-synuclein impairs normal dynamics of mitochondria in cell and animal models of Parkinson’s disease. J Neurochem 122:404–414. doi:10.1111/j.1471-4159.2012.07769.x PubMedCrossRef

Xiromerisiou G et al (2010) Genetic basis of Parkinson disease. Neurosurg Focus 28:E7. doi:10.3171/2009.10.FOCUS09220 PubMedCrossRef

Yokota T, Sugawara K, Ito K, Takahashi R, Ariga H, Mizusawa H (2003) Down regulation of DJ-1 enhances cell death by oxidative stress, ER stress, and proteasome inhibition. Biochem Biophys Res Commun 312:1342–1348PubMedCrossRef

Youle RJ, van der Bliek AM (2012) Mitochondrial fission, fusion, and stress. Science 337:1062–1065. doi:10.1126/science.1219855 PubMedCrossRef

Zhang J, Perry G, Smith MA, Robertson D, Olson SJ, Graham DG, Montine TJ (1999) Parkinson’s disease is associated with oxidative damage to cytoplasmic DNA and RNA in substantia nigra neurons. Am J Pathol 154:1423–1429. doi:10.1016/S0002-9440(10)65396-5 PubMedCentralPubMedCrossRef

Zhang L et al (2005a) Mitochondrial localization of the Parkinson’s disease related protein DJ-1: implications for pathogenesis. Hum Mol Genet 14:2063–2073. doi:10.1093/hmg/ddi211 PubMedCrossRef

Zhang W et al (2005b) Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. FASEB J 19:533–542. doi:10.1096/fj.04-2751com PubMedCrossRef

Zhang W et al (2007) Microglial PHOX and Mac-1 are essential to the enhanced dopaminergic neurodegeneration elicited by A30P and A53T mutant alpha-synuclein. Glia 55:1178–1188. doi:10.1002/glia.20532 PubMedCrossRef

Zimprich A et al (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44:601–607. doi:10.1016/j.neuron.2004.11.005 PubMedCrossRef

Titel: New insights on Parkinson’s disease genes: the link between mitochondria impairment and neuroinflammation
verfasst von: Dorit Trudler
Yuval Nash
Dan Frenkel
Publikationsdatum: 01.10.2015
Verlag: Springer Vienna
Erschienen in: Journal of Neural Transmission / Ausgabe 10/2015
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-015-1399-z

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