Mitochondrial Toxicant-Induced Neuronal Apoptosis in Parkinson’s Disease: What We Know so Far

References

• Pickrell AM, Youle RJ. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron. 2015;85(2):257–273. doi:10.1016/j.neuron.2014.12.007
   PubMed Web of Science ®Google Scholar
• Aubignat M, Tir M, Krystkowiak P. Les symptômes non-moteurs de la maladie de Parkinson de la physiopathologie au diagnostic précoce [Non-motor symptoms of Parkinson’s disease from pathophysiology to early diagnosis]. Rev Med Interne. 2021;42(4):251–257. French. doi:10.1016/j.revmed.2020.06.019
   PubMedGoogle Scholar
• Antony PM, Diederich NJ, Kruger R, Balling R. The hallmarks of Parkinson’s disease. FEBS J. 2013;280(23):5981–5993. doi:10.1111/febs.12335
   PubMed Web of Science ®Google Scholar
• Dugger BN, Dickson DW. Pathology of neurodegenerative diseases. Cold Spring Harb Perspect Biol. 2017;9(7):a028035. doi:10.1101/cshperspect.a028035
   PubMed Web of Science ®Google Scholar
• Zambrano K, Barba D, Castillo K, et al. Fighting Parkinson’s disease: the return of the mitochondria. Mitochondrion. 2022;64:34–44. doi:10.1016/j.mito.2022.02.003
   PubMed Web of Science ®Google Scholar
• Beitz JM. Parkinson’s disease: a review. Front Biosci. 2014;6(1):65–74. doi:10.2741/S415
   Google Scholar
• Bene R, Antic S, Budisic M, et al. Parkinson’s disease. Acta Clin Croat. 2009;48(3):377–380.
   PubMed Web of Science ®Google Scholar
• Latchoumycandane C, Anantharam V, Kitazawa M, Yang Y, Kanthasamy A, Kanthasamy AG. Protein kinase Cdelta is a key downstream mediator of manganese-induced apoptosis in dopaminergic neuronal cells. J Pharmacol Exp Ther. 2005;313(1):46–55. doi:10.1124/jpet.104.078469
   PubMed Web of Science ®Google Scholar
• Iannielli A, Bido S, Folladori L, et al. Pharmacological inhibition of necroptosis protects from dopaminergic neuronal cell death in Parkinson’s disease models. Cell Rep. 2018;22(8):2066–2079. doi:10.1016/j.celrep.2018.01.089
   PubMed Web of Science ®Google Scholar
• St-Pierre J, Buckingham JA, Roebuck SJ, Brand MD. Topology of superoxide production from different sites in the mitochondrial electron transport chain. J Biol Chem. 2002;277(47):44784–44790. doi:10.1074/jbc.M207217200
   PubMed Web of Science ®Google Scholar
• Muller FL, Liu Y, Van Remmen H. Complex III releases superoxide to both sides of the inner mitochondrial membrane. J Biol Chem. 2004;279(47):49064–49073. doi:10.1074/jbc.M407715200
   PubMed Web of Science ®Google Scholar
• Larsen SB, Hanss Z, Kruger R. The genetic architecture of mitochondrial dysfunction in Parkinson’s disease. Cell Tissue Res. 2018;373(1):21–37. doi:10.1007/s00441-017-2768-8
   PubMed Web of Science ®Google Scholar
• Gonzalez-Rodriguez P, Zampese E, Stout KA, et al. Disruption of mitochondrial complex I induces progressive parkinsonism. Nature. 2021;599(7886):650–656. doi:10.1038/s41586-021-04059-0
   PubMed Web of Science ®Google Scholar
• Monzio Compagnoni G, Di Fonzo A, Corti S, Comi GP, Bresolin N, Masliah E. The role of mitochondria in neurodegenerative diseases: the lesson from Alzheimer’s Disease and Parkinson’s Disease. Mol Neurobiol. 2020;57(7):2959–2980. doi:10.1007/s12035-020-01926-1
   PubMed Web of Science ®Google Scholar
• Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med. 2000;29(3–4):222–230. doi:10.1016/S0891-5849(00)00317-8
   PubMed Web of Science ®Google Scholar
• Meyer JN, Hartman JH, Mello DF. Mitochondrial toxicity. Toxicol Sci. 2018;162(1):15–23. doi:10.1093/toxsci/kfy008
   PubMed Web of Science ®Google Scholar
• Meyer JN, Chan SSL. Sources, mechanisms, and consequences of chemical-induced mitochondrial toxicity. Toxicology. 2017;391:2–4. doi:10.1016/j.tox.2017.06.002
   PubMed Web of Science ®Google Scholar
• Guo C, Sun L, Chen X, Zhang D. Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen Res. 2013;8(21):2003–2014. doi:10.3969/j.issn.1673-5374.2013.21.009
   PubMed Web of Science ®Google Scholar
• Sherer TB, Chowdhury S, Peabody K, Brooks DW. Overcoming obstacles in Parkinson’s disease. Mov Disord. 2012;27(13):1606–1611. doi:10.1002/mds.25260
   PubMed Web of Science ®Google Scholar
• Gazewood JD, Richards DR, Clebak K. Parkinson disease: an update. Am Fam Physician. 2013;87(4):267–273.
   PubMed Web of Science ®Google Scholar
• George JM, Jin H, Woods WS, Clayton DF. Characterization of a novel protein regulated during the critical period for song learning in the zebra finch. Neuron. 1995;15(2):361–372. doi:10.1016/0896-6273(95)90040-3
   PubMed Web of Science ®Google Scholar
• Iwai A, Masliah E, Yoshimoto M, et al. The precursor protein of non-A beta component of Alzheimer’s disease amyloid is a presynaptic protein of the central nervous system. Neuron. 1995;14(2):467–475. doi:10.1016/0896-6273(95)90302-X
   PubMed Web of Science ®Google Scholar
• Li KL, Huang HY, Ren H, Yang XL. Role of exosomes in the pathogenesis of inflammation in Parkinson’s disease. Neural Regen Res. 2022;17(9):1898–1906. doi:10.4103/1673-5374.335143
   PubMed Web of Science ®Google Scholar
• Moore DJ, West AB, Dawson VL, Dawson TM. Molecular pathophysiology of Parkinson’s disease. Annu Rev Neurosci. 2005;28:57–87. doi:10.1146/annurev.neuro.28.061604.135718
   PubMed Web of Science ®Google Scholar
• Latchoumycandane C, Anantharam V, Jin H, Kanthasamy A, Kanthasamy A. Dopaminergic neurotoxicant 6-OHDA induces oxidative damage through proteolytic activation of PKCdelta in cell culture and animal models of Parkinson’s disease. Toxicol Appl Pharmacol. 2011;256(3):314–323. doi:10.1016/j.taap.2011.07.021
   PubMed Web of Science ®Google Scholar
• Wichmann T, DeLong MR. Pathophysiology of parkinsonian motor abnormalities. Adv Neurol. 1993;60:53–61.
   PubMedGoogle Scholar
• Mottis A, Herzig S, Auwerx J. Mitocellular communication: shaping health and disease. Science. 2019;366(6467):827–832. doi:10.1126/science.aax3768
   PubMed Web of Science ®Google Scholar
• Osellame LD, Blacker TS, Duchen MR. Cellular and molecular mechanisms of mitochondrial function. Best Pract Res Clin Endocrinol Metab. 2012;26(6):711–723. doi:10.1016/j.beem.2012.05.003
   PubMed Web of Science ®Google Scholar
• Mitchell P. Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature. 1961;191(4784):144–148. doi:10.1038/191144a0
   PubMed Web of Science ®Google Scholar
• Jayasundara N. Ecological significance of mitochondrial toxicants. Toxicology. 2017;391:64–74. doi:10.1016/j.tox.2017.07.015
   PubMed Web of Science ®Google Scholar
• Pieczenik SR, Neustadt J. Mitochondrial dysfunction and molecular pathways of disease. Exp Mol Pathol. 2007;83(1):84–92. doi:10.1016/j.yexmp.2006.09.008
   PubMed Web of Science ®Google Scholar
• Friedlander RM. Apoptosis and caspases in neurodegenerative diseases. N Engl J Med. 2003;348(14):1365–1375. doi:10.1056/NEJMra022366
   PubMed Web of Science ®Google Scholar
• Badley AD, Dockrell D, Paya CV. Apoptosis in AIDS. Adv Pharmacol. 1997;41:271–294.
   PubMedGoogle Scholar
• Tatton WG, Olanow CW. Apoptosis in neurodegenerative diseases: the role of mitochondria. Biochim Biophys Acta. 1999;1410(2):195–213. doi:10.1016/S0005-2728(98)00167-4
   PubMed Web of Science ®Google Scholar
• Meyer JN, Leung MC, Rooney JP, et al. Mitochondria as a target of environmental toxicants. Toxicol Sci. 2013;134(1):1–17. doi:10.1093/toxsci/kft102
   PubMed Web of Science ®Google Scholar
• Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 1983;219(4587):979–980. doi:10.1126/science.6823561
   PubMed Web of Science ®Google Scholar
• Blum D, Torch S, Lambeng N, et al. Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson’s disease. Prog Neurobiol. 2001;65(2):135–172. doi:10.1016/s0301-0082(01)00003-x
   PubMed Web of Science ®Google Scholar
• Hisahara S, Shimohama S. Toxin-induced and genetic animal models of Parkinson’s disease. Parkinsons Dis. 2010;2011:951709. doi:10.4061/2011/951709
   PubMed Web of Science ®Google Scholar
• Nicotra A, Parvez SH. Cell death induced by MPTP, a substrate for monoamine oxidase B. Toxicology. 2000;153(1–3):157–166. doi:10.1016/S0300-483X(00)00311-5
   PubMed Web of Science ®Google Scholar
• Perry TL, Yong VW, Jones K, et al. Effects of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and its metabolite, N-methyl-4-phenylpyridinium ion, on dopaminergic nigrostriatal neurons in the mouse. Neurosci Lett. 1985;58(3):321–326. doi:10.1016/0304-3940(85)90074-6
   PubMed Web of Science ®Google Scholar
• Jackson-Lewis V, Przedborski S. Protocol for the MPTP mouse model of Parkinson’s disease. Nat Protoc. 2007;2(1):141–151. doi:10.1038/nprot.2006.342
   PubMed Web of Science ®Google Scholar
• Purisai MG, McCormack AL, Langston WJ, Johnston LC, Di Monte DA. Alpha-synuclein expression in the substantia nigra of MPTP-lesioned non-human primates. Neurobiol Dis. 2005;20(3):898–906. doi:10.1016/j.nbd.2005.05.028
   PubMed Web of Science ®Google Scholar
• Tysnes OB, Storstein A. Epidemiology of Parkinson’s disease. J Neural Transm. 2017;124(8):901–905. doi:10.1007/s00702-017-1686-y
   PubMed Web of Science ®Google Scholar
• Pathania A, Garg P, Sandhir R. Impaired mitochondrial functions and energy metabolism in MPTP-induced Parkinson’s disease: comparison of mice strains and dose regimens. Metab Brain Dis. 2021;36(8):2343–2357. doi:10.1007/s11011-021-00840-2
   PubMed Web of Science ®Google Scholar
• Blandini F, Armentero MT. Animal models of Parkinson’s disease. FEBS J. 2012;279(7):1156–1166. doi:10.1111/j.1742-4658.2012.08491.x
   PubMed Web of Science ®Google Scholar
• Ascenzi P, Di Masi A, Sciorati C, Clementi E. Peroxynitrite-An ugly biofactor? Biofactors. 2010;36(4):264–273. doi:10.1002/biof.103
   PubMed Web of Science ®Google Scholar
• Ahmad R, Hussain A, Ahsan H. Peroxynitrite: cellular pathology and implications in autoimmunity. J Immunoassay Immunochem. 2019;40(2):123–138. doi:10.1080/15321819.2019.1583109
   PubMedGoogle Scholar
• Dawson TM, Dawson VL. Nitric oxide signaling in neurodegeneration and cell death. Adv Pharmacol. 2018;82:57–83.
   PubMedGoogle Scholar
• Szabo C, Ischiropoulos H, Radi R. Peroxynitrite: biochemistry, pathophysiology and development of therapeutics. Nat Rev Drug Discov. 2007;6(8):662–680. doi:10.1038/nrd2222
   PubMed Web of Science ®Google Scholar
• Radi R, Cassina A, Hodara R. Nitric oxide and peroxynitrite interactions with mitochondria. Biol Chem. 2002;383(3–4):401–409. doi:10.1515/BC.2002.044
   PubMed Web of Science ®Google Scholar
• Radi R, Cassina A, Hodara R, Quijano C, Castro L. Peroxynitrite reactions and formation in mitochondria. Free Radic Biol Med. 2002;33(11):1451–1464. doi:10.1016/S0891-5849(02)01111-5
   PubMed Web of Science ®Google Scholar
• Radi R, Rodriguez M, Castro L, Telleri R. Inhibition of mitochondrial electron transport by peroxynitrite. Arch Biochem Biophys. 1994;308(1):89–95. doi:10.1006/abbi.1994.1013
   PubMed Web of Science ®Google Scholar
• Brown GC, Borutaite V. Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols. Biochim Biophys Acta. 2004;1658(1–2):44–49. doi:10.1016/j.bbabio.2004.03.016
   PubMed Web of Science ®Google Scholar
• Bolanos JP, Heales SJ, Land JM, Clark JB. Effect of peroxynitrite on the mitochondrial respiratory chain: differential susceptibility of neurones and astrocytes in primary culture. J Neurochem. 1995;64(5):1965–1972. doi:10.1046/j.1471-4159.1995.64051965.x
   PubMed Web of Science ®Google Scholar
• Guidarelli A, Fiorani M, Cantoni O. Enhancing effects of intracellular ascorbic acid on peroxynitrite-induced U937 cell death are mediated by mitochondrial events resulting in enhanced sensitivity to peroxynitrite-dependent inhibition of complex III and formation of hydrogen peroxide. Biochem J. 2004;378(Pt 3):959–966. doi:10.1042/bj20031167
   PubMedGoogle Scholar
• Cassina A, Radi R. Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch Biochem Biophys. 1996;328(2):309–316. doi:10.1006/abbi.1996.0178
   PubMed Web of Science ®Google Scholar
• Ebadi M, Sharma SK. Peroxynitrite and mitochondrial dysfunction in the pathogenesis of Parkinson’s disease. Antioxid Redox Signal. 2003;5(3):319–335. doi:10.1089/152308603322110896
   PubMed Web of Science ®Google Scholar
• Ebadi M, Sharma SK, Ghafourifar P, Brown-Borg H, El Refaey H. Peroxynitrite in the pathogenesis of Parkinson’s disease and the neuroprotective role of metallothioneins. Methods Enzymol. 2005;396:276–298.
   PubMed Web of Science ®Google Scholar
• Picon-Pages P, Garcia-Buendia J, Munoz FJ. Functions and dysfunctions of nitric oxide in brain. Biochim Biophys Acta Mol Basis Dis. 2019;1865(8):1949–1967. doi:10.1016/j.bbadis.2018.11.007
   PubMed Web of Science ®Google Scholar
• Torreilles F, Salman-Tabcheh S, Guerin M, Torreilles J. Neurodegenerative disorders: the role of peroxynitrite. Brain Res Brain Res Rev. 1999;30(2):153–163. doi:10.1016/S0165-0173(99)00014-4
   PubMedGoogle Scholar
• Chinta SJ, Andersen JK. Nitrosylation and nitration of mitochondrial complex I in Parkinson’s disease. Free Radic Res. 2011;45(1):53–58. doi:10.3109/10715762.2010.509398
   PubMed Web of Science ®Google Scholar
• Ara J, Przedborski S, Naini AB, et al. Inactivation of tyrosine hydroxylase by nitration following exposure to peroxynitrite and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Proc Natl Acad Sci U S A. 1998;95(13):7659–7663. doi:10.1073/pnas.95.13.7659
   PubMed Web of Science ®Google Scholar
• Bharath S, Andersen JK. Glutathione depletion in a midbrain-derived immortalized dopaminergic cell line results in limited tyrosine nitration of mitochondrial complex I subunits: implications for Parkinson’s disease. Antioxid Redox Signal. 2005;7(7–8):900–910. doi:10.1089/ars.2005.7.900
   PubMed Web of Science ®Google Scholar
• Zaheer F, Slevin JT. Trichloroethylene and Parkinson disease. Neurol Clin. 2011;29(3):657–665.
   PubMed Web of Science ®Google Scholar
• Bringmann G, God R, Feineis D, Janetzky B, Reichmann H. TaClo as a neurotoxic lead: improved synthesis, stereochemical analysis, and inhibition of the mitochondrial respiratory chain. J Neural Transm Suppl. 1995;46:245–254.
   PubMedGoogle Scholar
• Bringmann G, God R, Feineis D, et al. The TaClo concept: 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo), a new toxin for dopaminergic neurons. J Neural Transm Suppl. 1995;46:235–244.
   PubMedGoogle Scholar
• Bringmann G, Hille A. Endogenous alkaloids in man, VII: 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline--a potential chloral-derived indol alkaloid in man. Arch Pharm. 1990;323(9):567–569. doi:10.1002/ardp.19903230903
   PubMed Web of Science ®Google Scholar
• Kochen W, Kohlmuller D, De Biasi P, Ramsay R. The endogeneous formation of highly chlorinated tetrahydro-beta-carbolines as a possible causative mechanism in idiopathic Parkinson’s disease. Adv Exp Med Biol. 2003;527:253–263.
   PubMed Web of Science ®Google Scholar
• Yang Y, Pang B, Liu Z, et al. 1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) induces the apoptosis of dopaminergic neurons via oxidative stress and neuroinflammation. Oxid Med Cell Longev. 2019;2019:1292891. doi:10.1155/2019/1292891
   PubMed Web of Science ®Google Scholar
• Rausch WD, Abdel-mohsen M, Koutsilieri E, Chan WW, Bringmann G. Studies of the potentially endogenous toxin TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline) in neuronal and glial cell cultures. J Neural Transm Suppl. 1995;46:255–263.
   PubMedGoogle Scholar
• Keane PC, Kurzawa M, Blain PG, Morris CM. Mitochondrial dysfunction in Parkinson’s disease. Parkinsons Dis. 2011;2011:716871. doi:10.4061/2011/716871
   PubMedGoogle Scholar
• Keane PC, Hanson PS, Patterson L, et al. Trichloroethylene and its metabolite TaClo lead to degeneration of substantia nigra dopaminergic neurones: effects in wild type and human A30P mutant alpha-synuclein mice. Neurosci Lett. 2019;711:134437. doi:10.1016/j.neulet.2019.134437
   PubMed Web of Science ®Google Scholar
• Shokrzadeh M, Shaki F, Mohammadi E, Rezagholizadeh N, Ebrahimi F. Edaravone decreases paraquat toxicity in a549 cells and lung isolated mitochondria. Iran J Pharm Res. 2014;13(2):675–681.
   PubMed Web of Science ®Google Scholar
• Cocheme HM, Murphy MP. Chapter 22 the uptake and interactions of the redox cycler paraquat with mitochondria. Methods Enzymol. 2009;456:395–417.
   PubMed Web of Science ®Google Scholar
• Yang W, Tiffany-Castiglioni E. Paraquat-induced apoptosis in human neuroblastoma SH-SY5Y cells: involvement of p53 and mitochondria. J Toxicol Environ Health A. 2008;71(4):289–299. doi:10.1080/15287390701738467
   PubMed Web of Science ®Google Scholar
• Chinta SJ, Woods G, Demaria M, et al. Cellular senescence is induced by the environmental neurotoxin paraquat and contributes to neuropathology linked to Parkinson’s disease. Cell Rep. 2018;22(4):930–940. doi:10.1016/j.celrep.2017.12.092
   PubMed Web of Science ®Google Scholar
• Zuo Y, Xie J, Li X, et al. Ferritinophagy-mediated ferroptosis involved in paraquat-induced neurotoxicity of dopaminergic neurons: implication for neurotoxicity in PD. Oxid Med Cell Longev. 2021;2021:9961628. doi:10.1155/2021/9961628
   PubMedGoogle Scholar
• Henchcliffe C, Beal MF. Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat Clin Pract Neurol. 2008;4(11):600–609. doi:10.1038/ncpneuro0924
   PubMedGoogle Scholar
• Corasaniti MT, Strongoli MC, Rotiroti D, Bagetta G, Nistico G. Paraquat: a useful tool for the in vivo study of mechanisms of neuronal cell death. Pharmacol Toxicol. 1998;83(1):1–7. doi:10.1111/j.1600-0773.1998.tb01434.x
   PubMedGoogle Scholar
• Manning-Bog AB, McCormack AL, Li J, Uversky VN, Fink AL, Di Monte DA. The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein. J Biol Chem. 2002;277(3):1641–1644. doi:10.1074/jbc.C100560200
   PubMed Web of Science ®Google Scholar
• Radad K, Al-Shraim M, Al-Emam A, et al. Rotenone: from modelling to implication in Parkinson’s disease. Folia Neuropathol. 2019;57(4):317–326. doi:10.5114/fn.2019.89857
   PubMed Web of Science ®Google Scholar
• Talpade DJ, Greene JG, Higgins DS Jr., Greenamyre JT. In vivo labeling of mitochondrial complex I (NADH: ubiquinoneoxidoreductase) in rat brain using [(3)H]dihydrorotenone. J Neurochem. 2008;75(6):2611–2621. doi:10.1046/j.1471-4159.2000.0752611.x
   Google Scholar
• Schuler F, Casida JE. Functional coupling of PSST and ND1 subunits in NADH: ubiquinoneoxidoreductase established by photoaffinity labeling. Biochim Biophys Acta. 2001;1506(1):79–87. doi:10.1016/S0005-2728(01)00183-9
   PubMed Web of Science ®Google Scholar
• Yarmohammadi F, Wallace Hayes A, Najafi N, Karimi G. The protective effect of natural compounds against rotenone-induced neurotoxicity. J Biochem Mol Toxicol. 2020;34(12):e22605. doi:10.1002/jbt.22605
   PubMed Web of Science ®Google Scholar
• Li N, Ragheb K, Lawler G, et al. Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. J Biol Chem. 2003;278(10):8516–8525. doi:10.1074/jbc.M210432200
   PubMed Web of Science ®Google Scholar
• Landau R, Halperin R, Sullivan P, et al. The rat rotenone model reproduces the abnormal pattern of central catecholamine metabolism found in Parkinson’s disease. Dis Model Mech. 2022;15(1). doi:10.1242/dmm.049082
   PubMed Web of Science ®Google Scholar
• Sharma M, Kaur J, Rakshe S, Sharma N, Khunt D, Khairnar A. Intranasal exposure to low-dose rotenone induced alpha-synuclein accumulation and Parkinson’s like symptoms without loss of dopaminergic neurons. Neurotox Res. 2022;40(1):215–229. doi:10.1007/s12640-021-00436-9
   PubMed Web of Science ®Google Scholar
• Mohammadi H, Ghassemi-Barghi N, Malakshah O, Ashari S. Pyrethroid exposure and neurotoxicity: a mechanistic approach. Arh Hig Rada Toksikol. 2019;70(2):74–89. doi:10.2478/aiht-2019-70-3263
   PubMed Web of Science ®Google Scholar
• Gassner B, Wuthrich A, Scholtysik G, Solioz M. The pyrethroids permethrin and cyhalothrin are potent inhibitors of the mitochondrial complex I. J Pharmacol Exp Ther. 1997;281(2):855–860.
   PubMed Web of Science ®Google Scholar
• Hirano T, Suzuki N, Ikenaka Y, Hoshi N, Tabuchi Y. Neurotoxicity of a pyrethroid pesticide deltamethrin is associated with the imbalance in proteolytic systems caused by mitophagy activation and proteasome inhibition. Toxicol Appl Pharmacol. 2021;430:115723. doi:10.1016/j.taap.2021.115723
   PubMed Web of Science ®Google Scholar
• Chen D, Huang X, Liu L, Shi N. Deltamethrin induces mitochondrial membrane permeability and altered expression of cytochrome C in rat brain. J Appl Toxicol. 2007;27(4):368–372. doi:10.1002/jat.1215
   PubMed Web of Science ®Google Scholar
• Agrawal S, Singh A, Tripathi P, Mishra M, Singh PK, Singh MP. Cypermethrin-induced nigrostriatal dopaminergic neurodegeneration alters the mitochondrial function: a proteomics study. Mol Neurobiol. 2015;51(2):448–465. doi:10.1007/s12035-014-8696-7
   PubMed Web of Science ®Google Scholar
• Park YS, Park JH, Ko J, Shin IC, Koh HC. mTOR inhibition by rapamycin protects against deltamethrin-induced apoptosis in PC12 Cells. Environ Toxicol. 2017;32(1):109–121. doi:10.1002/tox.22216
   PubMed Web of Science ®Google Scholar
• Gozzelino R, Arosio P. Iron homeostasis in health and disease. Int J Mol Sci. 2016;17(1):130. doi:10.3390/ijms17010130
   PubMed Web of Science ®Google Scholar
• Baranwal AK, Singhi SC. Acute iron poisoning: management guidelines. Indian Pediatr. 2003;40(6):534–540.
   PubMedGoogle Scholar
• Farrall AJ, Wardlaw JM. Blood-brain barrier: ageing and microvascular disease--systematic review and meta-analysis. Neurobiol Aging. 2009;30(3):337–352. doi:10.1016/j.neurobiolaging.2007.07.015
   PubMed Web of Science ®Google Scholar
• Conde JR, Streit WJ. Microglia in the aging brain. J Neuropathol Exp Neurol. 2006;65(3):199–203. doi:10.1097/01.jnen.0000202887.22082.63
   PubMed Web of Science ®Google Scholar
• Ward RJ, Zucca FA, Duyn JH, Crichton RR, Zecca L. The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol. 2014;13(10):1045–1060. doi:10.1016/S1474-4422(14)70117-6
   PubMed Web of Science ®Google Scholar
• Carocci A, Catalano A, Sinicropi MS, Genchi G. Oxidative stress and neurodegeneration: the involvement of iron. Biometals. 2018;31(5):715–735. doi:10.1007/s10534-018-0126-2
   PubMed Web of Science ®Google Scholar
• Lhermitte J, Kraus WM, McAlpine D. Original papers: on the occurrence of abnormal deposits of iron in the brain in parkinsonism with special reference to its localisation. J Neurol Psychopathol. 1924;5(19):195–208. doi:10.1136/jnnp.s1-5.19.195
   PubMedGoogle Scholar
• Salazar J, Mena N, Hunot S, et al. Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson’s disease. Proc Natl Acad Sci U S A. 2008;105(47):18578–18583. doi:10.1073/pnas.0804373105
   PubMed Web of Science ®Google Scholar
• Nunez MT, Chana-Cuevas P. New perspectives in iron chelation therapy for the treatment of neurodegenerative diseases. Pharmaceuticals. 2018;11(4):109. doi:10.3390/ph11040109
   Web of Science ®Google Scholar
• Devos D, Moreau C, Devedjian JC, et al. Targeting chelatable iron as a therapeutic modality in Parkinson’s disease. Antioxid Redox Signal. 2014;21(2):195–210. doi:10.1089/ars.2013.5593
   PubMed Web of Science ®Google Scholar
• Mastroberardino PG, Hoffman EK, Horowitz MP, et al. A novel transferrin/TfR2-mediated mitochondrial iron transport system is disrupted in Parkinson’s disease. Neurobiol Dis. 2009;34(3):417–431. doi:10.1016/j.nbd.2009.02.009
   PubMed Web of Science ®Google Scholar
• Galvin JE, Giasson B, Hurtig HI, Lee VM, Trojanowski JQ. Neurodegeneration with brain iron accumulation, type 1 is characterized by alpha-, beta-, and gamma-synuclein neuropathology. Am J Pathol. 2000;157(2):361–368. doi:10.1016/S0002-9440(10)64548-8
   PubMed Web of Science ®Google Scholar
• Wakabayashi K, Fukushima T, Koide R, et al. Juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease) with diffuse neurofibrillary and lewy body pathology. Acta Neuropathol. 2000;99(3):331–336. doi:10.1007/s004010050049
   PubMed Web of Science ®Google Scholar
• Uversky VN. Neuropathology, biochemistry, and biophysics of alpha-synuclein aggregation. J Neurochem. 2007;103(1):17–37. doi:10.1111/j.1471-4159.2007.04764.x
   PubMed Web of Science ®Google Scholar
• Zecca L, Youdim MB, Riederer P, Connor JR, Crichton RR. Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci. 2004;5(11):863–873. doi:10.1038/nrn1537
   PubMed Web of Science ®Google Scholar
• Koeppen AH. The history of iron in the brain. J Neurol Sci. 1995;134:1–9. doi:10.1016/0022-510X(95)00202-D
   PubMed Web of Science ®Google Scholar
• Sanchez-Iglesias S, Soto-Otero R, Iglesias-Gonzalez J, Barciela-Alonso MC, Bermejo-Barrera P, Mendez-Alvarez E. Analysis of brain regional distribution of aluminium in rats via oral and intraperitoneal administration. J Trace Elem Med Biol. 2007;Suppl 21:31–34. doi:10.1016/j.jtemb.2007.09.010
   Web of Science ®Google Scholar
• Johnson VJ, Kim SH, Sharma RP. Aluminum-maltolate induces apoptosis and necrosis in neuro-2a cells: potential role for p53 signaling. Toxicol Sci. 2005;83(2):329–339. doi:10.1093/toxsci/kfi028
   PubMed Web of Science ®Google Scholar
• Kumar V, Gill KD. Oxidative stress and mitochondrial dysfunction in aluminium neurotoxicity and its amelioration: a review. Neurotoxicology. 2014;41:154–166. doi:10.1016/j.neuro.2014.02.004
   PubMed Web of Science ®Google Scholar
• Savory J, Herman MM, Ghribi O. Intracellular mechanisms underlying aluminum-induced apoptosis in rabbit brain. J Inorg Biochem. 2003;97(1):151–154. doi:10.1016/S0162-0134(03)00258-7
   PubMed Web of Science ®Google Scholar
• Oshima E, Ishihara T, Yokota O, et al. Accelerated tau aggregation, apoptosis and neurological dysfunction caused by chronic oral administration of aluminum in a mouse model of tauopathies. Brain Pathol. 2013;23(6):633–644. doi:10.1111/bpa.12059
   PubMed Web of Science ®Google Scholar
• Sanchez-Iglesias S, Mendez-Alvarez E, Iglesias-Gonzalez J, et al. Brain oxidative stress and selective behaviour of aluminium in specific areas of rat brain: potential effects in a 6-OHDA-induced model of Parkinson’s disease. J Neurochem. 2009;109(3):879–888. doi:10.1111/j.1471-4159.2009.06019.x
   PubMed Web of Science ®Google Scholar
• Sadeghi L, Tanwir F, Yousefi Babadi V. Physiological and biochemical effects of echium amoenum extract on Mn(2+)-imposed Parkinson like disorder in rats. Adv Pharm Bull. 2018;8(4):705–713. doi:10.15171/apb.2018.079
   PubMed Web of Science ®Google Scholar
• Burton NC, Schneider JS, Syversen T, Guilarte TR. Effects of chronic manganese exposure on glutamatergic and GABAergic neurotransmitter markers in the nonhuman primate brain. Toxicol Sci. 2009;111(1):131–139. doi:10.1093/toxsci/kfp124
   PubMed Web of Science ®Google Scholar
• Ali SF, Duhart HM, Newport GD, Lipe GW, Slikker W Jr. Manganese-induced reactive oxygen species: comparison between Mn+2 and Mn+3. Neurodegeneration. 1995;4(3):329–334. doi:10.1016/1055-8330(95)90023-3
   PubMedGoogle Scholar
• Dobson AW, Weber S, Dorman DC, Lash LK, Erikson KM, Aschner M. Oxidative stress is induced in the rat brain following repeated inhalation exposure to manganese sulfate. Biol Trace Elem Res. 2003;93(1–3):113–126. doi:10.1385/BTER:93:1-3:113
   PubMed Web of Science ®Google Scholar
• Erikson KM, Dorman DC, Lash LH, Dobson AW, Aschner M. Airborne manganese exposure differentially affects end points of oxidative stress in an age- and sex-dependent manner. Biol Trace Elem Res. 2004;100(1):49–62. doi:10.1385/BTER:100:1:049
   PubMed Web of Science ®Google Scholar
• Milatovic D, Yin Z, Gupta RC, et al. Manganese induces oxidative impairment in cultured rat astrocytes. Toxicol Sci. 2007;98(1):198–205. doi:10.1093/toxsci/kfm095
   PubMed Web of Science ®Google Scholar
• Galvani P, Fumagalli P, Santagostino A. Vulnerability of mitochondrial complex I in PC12 cells exposed to manganese. Eur J Pharmacol. 1995;293(4):377–383. doi:10.1016/0926-6917(95)90058-6
   PubMed Web of Science ®Google Scholar
• Zwingmann C, Leibfritz D, Hazell AS. Energy metabolism in astrocytes and neurons treated with manganese: relation among cell-specific energy failure, glucose metabolism, and intercellular trafficking using multinuclear NMR-spectroscopic analysis. J Cereb Blood Flow Metab. 2003;23(6):756–771. doi:10.1097/01.WCB.0000056062.25434.4D
   PubMed Web of Science ®Google Scholar
• Singh J, Husain R, Tandon SK, Seth PK, Chandra SV. Biochemical and histopathological alterations in early manganese toxicity in rats. Environ Physiol Biochem. 1974;4(1):16–23.
   PubMedGoogle Scholar
• Sloot WN, Gramsbergen JB. Axonal transport of manganese and its relevance to selective neurotoxicity in the rat basal ganglia. Brain Res. 1994;657(1–2):124–132. doi:10.1016/0006-8993(94)90959-8
   PubMed Web of Science ®Google Scholar
• Sloot WN, van der Sluijs-Gelling AJ, Gramsbergen JB. Selective lesions by manganese and extensive damage by iron after injection into rat striatum or hippocampus. J Neurochem. 2008;62(1):205–216. doi:10.1046/j.1471-4159.1994.62010205.x
   Google Scholar
• Parenti M, Rusconi L, Cappabianca V, Parati EA, Groppetti A. Role of dopamine in manganese neurotoxicity. Brain Res. 1988;473(2):236–240. doi:10.1016/0006-8993(88)90852-9
   PubMed Web of Science ®Google Scholar
• Gavin CE, Gunter KK, Gunter TE. Manganese and calcium transport in mitochondria: implications for manganese toxicity. Neurotoxicology. 1999;20(2–3):445–453.
   PubMed Web of Science ®Google Scholar
• Dias V, Junn E, Mouradian MM. The role of oxidative stress in Parkinson’s disease. J Parkinsons Dis. 2013;3(4):461–491. doi:10.3233/JPD-130230
   PubMedGoogle Scholar
• Erekat NS. Apoptosis and its role in Parkinson’s Disease. In: Stoker TB, Greenland JC, editors. Parkinson’s Disease: Pathogenesis and Clinical Aspects. Brisbane (AU): Exon Publications; 2018.
   Google Scholar
• Mizuno Y, Saitoh T, Sone N. Inhibition of mitochondrial NADH-ubiquinone oxidoreductase activity by 1-methyl-4-phenylpyridinium ion. Biochem Biophys Res Commun. 1987;143(1):294–299. doi:10.1016/0006-291X(87)90664-4
   PubMed Web of Science ®Google Scholar
• Wang YM, Pu P, Le WD. ATP depletion is the major cause of MPP+ induced dopamine neuronal death and worm lethality in alpha-synuclein transgenic C. elegans. Neurosci Bull. 2007;23(6):329–335. doi:10.1007/s12264-007-0049-3
   PubMedGoogle Scholar
• Gash DM, Rutland K, Hudson NL, et al. Trichloroethylene: Parkinsonism and complex 1 mitochondrial neurotoxicity. Ann Neurol. 2008;63(2):184–192. doi:10.1002/ana.21288
   PubMed Web of Science ®Google Scholar
• Liu M, Choi DY, Hunter RL, et al. Trichloroethylene induces dopaminergic neurodegeneration in fisher 344 rats. J Neurochem. 2010;112(3):773–783. doi:10.1111/j.1471-4159.2009.06497.x
   PubMed Web of Science ®Google Scholar
• Liu M, Shin EJ, Dang DK, et al. Trichloroethylene and Parkinson’s Disease: risk assessment. Mol Neurobiol. 2018;55(7):6201–6214. doi:10.1007/s12035-017-0830-x
   PubMed Web of Science ®Google Scholar
• Martinez-Finley EJ, Gavin CE, Aschner M, Gunter TE. Manganese neurotoxicity and the role of reactive oxygen species. Free Radic Biol Med. 2013;62:65–75. doi:10.1016/j.freeradbiomed.2013.01.032
   PubMed Web of Science ®Google Scholar
• Gubellini P, Picconi B, Di Filippo M, Calabresi P. Downstream mechanisms triggered by mitochondrial dysfunction in the basal ganglia: from experimental models to neurodegenerative diseases. Biochim Biophys Acta. 2010;1802(1):151–161. doi:10.1016/j.bbadis.2009.08.001
   PubMed Web of Science ®Google Scholar
• Wolozin B, Golts N. Iron and Parkinson’s disease. Neuroscientist. 2002;8(1):22–32. doi:10.1177/107385840200800107
   PubMed Web of Science ®Google Scholar
• Shi L, Huang C, Luo Q, et al. The association of iron and the pathologies of Parkinson’s Diseases in MPTP/MPP(+)-induced neuronal degeneration in non-human primates and in cell culture. Front Aging Neurosci. 2019;11:215. doi:10.3389/fnagi.2019.00215
   PubMed Web of Science ®Google Scholar
• Sherer TB, Betarbet R, Testa CM, et al. Mechanism of toxicity in rotenone models of Parkinson’s disease. J Neurosci. 2003;23(34):10756–10764. doi:10.1523/JNEUROSCI.23-34-10756.2003
   PubMed Web of Science ®Google Scholar
• Greenamyre JT, Betarbet R, Sherer TB. The rotenone model of Parkinson’s disease: genes, environment and mitochondria. Parkinsonism Relat Disord. 2003;9(Suppl 2):S59–S64. doi:10.1016/S1353-8020(03)00023-3
   PubMedGoogle Scholar
• Perier C, Bove J, Vila M, Przedborski S. The rotenone model of Parkinson’s disease. Trends Neurosci. 2003;26(7):345–346. doi:10.1016/S0166-2236(03)00144-9
   PubMed Web of Science ®Google Scholar
• Tawara T, Fukushima T, Hojo N, et al. Effects of paraquat on mitochondrial electron transport system and catecholamine contents in rat brain. Arch Toxicol. 1996;70(9):585–589. doi:10.1007/s002040050316
   PubMed Web of Science ®Google Scholar
• Cocheme HM, Murphy MP. Complex I is the major site of mitochondrial superoxide production by paraquat. J Biol Chem. 2008;283(4):1786–1798. doi:10.1074/jbc.M708597200
   PubMed Web of Science ®Google Scholar
• Yamada K, Fukushima T. Mechanism of cytotoxicity of paraquat. II. Organ specificity of paraquat-stimulated lipid peroxidation in the inner membrane of mitochondria. Exp Toxicol Pathol. 1993;45(5–6):375–380. doi:10.1016/S0940-2993(11)80433-1
   PubMed Web of Science ®Google Scholar
• Elwan MA, Richardson JR, Guillot TS, Caudle WM, Miller GW. Pyrethroid pesticide-induced alterations in dopamine transporter function. Toxicol Appl Pharmacol. 2006;211(3):188–197. doi:10.1016/j.taap.2005.06.003
   PubMed Web of Science ®Google Scholar
• Hansen MRH, Jors E, Lander F, et al. Neurological deficits after long-term pyrethroid exposure. Environ Health Insights. 2017;11:1178630217700628. doi:10.1177/1178630217700628
   Web of Science ®Google Scholar