A. H. Schapira, J. M. Cooper, D. Dexter, P. Jenner, J. B. Clark et al., MITOCHONDRIAL COMPLEX I DEFICIENCY IN PARKINSON'S DISEASE, The Lancet, vol.333, issue.8649, p.1269, 1989.

A. H. Schapira, J. M. Cooper, D. Dexter, J. B. Clark, P. Jenner et al., Mitochondrial Complex I Deficiency in Parkinson's Disease, Journal of Neurochemistry, vol.54, issue.3, pp.823-827, 1990.

M. T. Lin and M. F. Beal, Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases, Nature, vol.443, issue.7113, pp.787-795, 2006.

H. Büeler, Impaired mitochondrial dynamics and function in the pathogenesis of Parkinson's disease, Experimental Neurology, vol.218, issue.2, pp.235-246, 2009.

A. Bose and M. F. Beal, Mitochondrial dysfunction in Parkinson's disease, Journal of Neurochemistry, vol.139, pp.216-231, 2016.

. Neurochem, , vol.139, pp.216-231, 2016.

F. A. Zucca, J. Segura-aguilar, E. Ferrari, P. Muñoz, I. Paris et al.,

L. Sarna, L. Casella, and . Zecca, Interactions of iron, dopamine and neuromelanin 480 pathways in brain aging and Parkinson's disease, Prog. Neurobiol, p.481, 2015.

E. Sofic, P. Riederer, H. Heinsen, H. Beckmann, G. P. Reynolds et al., Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain, Journal of Neural Transmission, vol.74, issue.3, pp.199-205, 1988.

M. B. Hebenstreit and . Youdim, Increased iron (III) and total iron content in post 484 mortem substantia nigra of parkinsonian brain, J. Neural Transm, vol.74, pp.485-199, 1988.

H. Mochizuki and T. Yasuda, Iron accumulation in Parkinson?s disease, Journal of Neural Transmission, vol.119, issue.12, pp.1511-1514, 2012.

. Transm, , vol.119, pp.1511-1514, 2012.

C. W. Olanow and K. S. Mcnaught, Ubiquitin?proteasome system and Parkinson's disease, Movement Disorders, vol.21, issue.11, pp.1806-1823, 2006.

, Parkinson's disease, Mov. Disord, vol.21, 2006.

Q. Zheng, T. Huang, L. Zhang, Y. Zhou, H. Luo et al., Dysregulation of Ubiquitin-Proteasome System in Neurodegenerative Diseases, Frontiers in Aging Neuroscience, vol.8, p.492, 2016.

Q. Zheng, T. Huang, L. Zhang, Y. Zhou, H. Luo et al., Dysregulation of Ubiquitin-Proteasome System in Neurodegenerative Diseases, Frontiers in Aging Neuroscience, vol.8, 2016.

, Diseases., Front. Aging Neurosci, vol.8, p.303, 2016.

P. Jenner, D. T. Dexter, J. Sian, A. H. Schapira, and C. D. Marsden, Oxidative stress as a cause of nigral cell death in Parkinson's disease and incidental lewy body disease, Annals of Neurology, vol.32, issue.S1, pp.S82-S87, 1992.

E. C. Hirsch, Does Oxidative Stress Participate in Nerve Cell Death in 499

, Parkinson's Disease?, Eur. Neurol, vol.33, pp.52-59, 1993.

P. Jenner, Oxidative stress in Parkinson's disease, Ann. Neurol, vol.53, p.501, 2003.

. S26-s38,

A. Garcia-garcia, L. Zavala-flores, H. Rodriguez-rocha, and R. Franco, Thiol-Redox Signaling, Dopaminergic Cell Death, and Parkinson's Disease, Antioxidants & Redox Signaling, vol.17, issue.12, pp.1764-1784, 2012.

A. Garcia-garcia, L. Zavala-flores, H. Rodriguez-rocha, and R. Franco, Thiol-Redox Signaling, Dopaminergic Cell Death, and Parkinson's Disease, Antioxidants & Redox Signaling, vol.17, issue.12, pp.1764-1784, 2012.

W. M. Johnson, A. L. Wilson-delfosse, S. G. Chen, and J. J. , The Roles of Redox Enzymes in Parkinson?s Disease: Focus on Glutaredoxin, Therapeutic Targets for Neurological Diseases, p.507, 2015.

, Radiation-induced cognitive impairment, Therapeutic Targets for Neurological Diseases, vol.2, 2015.

A. Ray, N. Sehgal, S. Karunakaran, G. Rangarajan, and V. Ravindranath, MPTP 509 activates ASK1-p38 MAPK signaling pathway through TNF-dependent Trx1 510 oxidation in parkinsonism mouse model, Free Radic, Biol. Med, vol.87, pp.312-325, 2015.

L. Durgadoss, P. Nidadavolu, R. K. Valli, U. Saeed, M. Mishra et al.,

. Ravindranath, Redox modification of Akt mediated by the dopaminergic 514 neurotoxin MPTP, in mouse midbrain, leads to down-regulation of pAkt, p.515

, FASEB J, vol.26, pp.1473-1483, 2012.

E. M. Allen and J. J. , Protein-thiol oxidation and cell death: regulatory role 517 of glutaredoxins, Antioxid. Redox Signal, vol.17, pp.1748-63, 2012.

S. A. Gravina and J. J. , Thioltransferase is a specific glutathionyl mixed-520 disulfide oxidoreductase, Biochemistry, vol.32, pp.3368-3376, 1993.

W. M. Johnson, C. Yao, S. L. Siedlak, W. Wang, X. Zhu et al.,

J. J. Wilson-delfosse, S. G. Mieyal, and . Chen, Glutaredoxin deficiency exacerbates 524 neurodegeneration in C. elegans models of Parkinson's disease

. Genet, , vol.24, pp.1322-1357, 2015.

U. Saeed, A. Ray, R. K. Valli, A. M. Kumar, and V. Ravindranath, DJ-1 loss by 527 glutaredoxin but not glutathione depletion triggers Daxx translocation and cell 528 death, Antioxid. Redox Signal, vol.13, pp.127-144, 2010.

D. Grimm, M. A. Kay, and J. A. Kleinschmidt, Helper virus-free, optically controllable, 530 and two-plasmid-based production of adeno-associated virus vectors of 531 serotypes 1 to 6, Mol. Ther, vol.7, issue.03, pp.95-104, 2003.

C. Towne and P. Aebischer, Lentiviral and Adeno-Associated Vector-Based 534

, Therapy for Motor Neuron Disease Through RNAi, vol.535, pp.87-108, 2009.

C. Towne, C. Raoul, B. L. Schneider, and P. Aebischer, Systemic AAV6 Delivery, p.537

, Mediating RNA Interference Against, vol.1

, Does Not Alter Disease Progression in fALS Mice, Mol. Ther, vol.16, p.1025, 2008.

C. Leys, C. Ley, O. Klein, P. Bernard, and L. Licata, Detecting outliers: Do not use 541 standard deviation around the mean, use absolute deviation around the 542 median, J. Exp. Soc. Psychol, vol.49, pp.764-766, 2013.

C. Borlongan and P. Sanberg, Elevated body swing test: a new behavioral 545 parameter for rats with 6-hydroxydopamine-induced hemiparkinsonism

. Neurosci, , p.15, 1995.

J. Hirrlinger, J. M. Gutterer, L. Kussmaul, B. Hamprecht, and R. Dringen, Microglial 548 Cells in Culture Express a Prominent Glutathione System for the Defense 549 against Reactive Oxygen Species, Dev. Neurosci, vol.22, pp.384-392, 2000.

R. Dringen, Metabolism and functions of glutathione in brain, Prog. Neurobiol, vol.552, pp.649-671, 2000.

M. Persson, M. Brantefjord, E. Hansson, and L. Rönnbäck, Lipopolysaccharide 554 increases microglial GLT-1 expression and glutamate uptake capacity in vitro 555 by a mechanism dependent on TNF-?, Glia, vol.51, 2005.

J. M. Dopp, T. A. Sarafian, F. M. Spinella, M. A. Kahn, H. Shau et al., 558 Expression of the p75 TNF receptor is linked to TNF-induced NFkappaB 559 translocation and oxyradical neutralization in glial cells, Neurochem. Res, vol.27, pp.1535-1542, 2002.

T. Breidert, J. Callebert, M. T. Heneka, G. Landreth, J. M. Launay et al., , vol.562

, Protective action of the peroxisome proliferator-activated receptor-? agonist 563 pioglitazone in a mouse model of Parkinson's disease, J. Neurochem, vol.82, pp.615-624, 2002.

S. Balijepalli, P. S. Tirumalai, K. Swamy, M. R. Boyd, and J. J. ,

. Ravindranath, Rat brain thioltransferase: regional distribution, immunological 567 characterization, and localization by fluorescent in situ hybridization

. Neurochem, , vol.72, pp.1170-1178, 1999.

M. Deponte, Glutathione catalysis and the reaction mechanisms of glutathione-570 dependent enzymes, Biochim. Biophys. Acta -Gen. Subj, vol.1830, pp.3217-571, 2013.

M. E. Rice and I. Russo-menna, Differential compartmentalization of brain 573 ascorbate and glutathione between neurons and glia, vol.82, pp.1213-1223, 1997.

R. Dringen, B. Pfeiffer, and B. Hamprecht, Synthesis of the antioxidant glutathione 576 in neurons: Supply by astrocytes of CysGly as precursor for neuronal 577

, J. Neurosci, vol.19, pp.562-569, 1999.

S. Gutbier, A. S. Spreng, J. Delp, S. Schildknecht, C. Karreman et al.,

M. Brunner, M. Groettrup, and . Leist, Prevention of neuronal apoptosis by 581 astrocytes through thiol-mediated stress response modulation and accelerated 582 recovery from proteotoxic stress, Cell Death Differ, vol.583, pp.2101-2117, 2018.

X. Yang, H. Yang, F. Wu, Z. Qi, J. Li et al., Mn inhibits 585 GSH synthesis via downregulation of neuronal EAAC1 and astrocytic xCT to 586 cause oxidative damage in the striatum of mice, Oxid. Med. Cell. Longev, p.587, 2018.

D. F. Aschauer, S. Kreuz, and S. Rumpel, Analysis of transduction efficiency, 589 tropism and axonal transport of AAV serotypes 1, 2, 5, 6, 8 and 9 in the mouse 590 brain, PLoS One, vol.8, 2013.

M. López-grueso, R. González-ojeda, and R. Requejo-aguilar,

J. Fuentes-almagro, J. A. Muntané, C. Bárcena, and . Padilla, Thioredoxin and 594 glutaredoxin regulate metabolism through different multiplex thiol switches, p.595

, Redox Biol, vol.21, p.101049, 2019.

O. Miller, J. B. Behring, S. L. Siedlak, S. Jiang, R. Matsui et al., , p.597

X. Bachschmid and J. J. Zhu, Upregulation of Glutaredoxin-1 Activates 598

, Microglia and Promotes Neurodegeneration: Implications for Parkinson, p.599

. Disease, Antioxid. Redox Signal, vol.25, 2016.

U. Saeed, L. Durgadoss, R. K. Valli, D. C. Joshi, P. G. Joshi et al., , p.602

, Knockdown of cytosolic glutaredoxin 1 leads to loss of mitochondrial 603 membrane potential: implication in neurodegenerative diseases, PLoS One. 3, vol.604, p.2459, 2008.

R. S. Kenchappa and V. Ravindranath, Glutaredoxin is essential for maintenance 606 of brain mitochondrial complex I: studies with MPTP, FASEB J, vol.17, pp.717-607, 2003.

L. Diwakar, R. S. Kenchappa, J. Annepu, and V. Ravindranath, Downregulation of 609 glutaredoxin but not glutathione loss leads to mitochondrial dysfunction in 610 female mice CNS: Implications in excitotoxicity, Neurochem. Int, vol.51, pp.37-611, 2007.

C. Klein and A. Westenberger, Genetics of Parkinson's disease, Cold Spring Harb

, Perspect. Med, vol.2, p.8888, 2012.

R. Taipa, C. Pereira, I. Reis, I. Alonso, A. Bastos-lima et al., , p.615

. Magalhães, DJ-1 linked parkinsonism (PARK7) is associated with Lewy body 616 pathology, Brain, vol.139, pp.1680-1687, 2016.

W. M. Johnson, C. Yao, S. L. Siedlak, W. Wang, X. Zhu et al.,

J. J. Wilson-delfosse, S. G. Mieyal, and . Chen, Glutaredoxin deficiency exacerbates 619 neurodegeneration in C. elegans models of Parkinson's disease

. Genet, , vol.24, pp.1322-1357, 2015.

S. Karunakaran, L. Diwakar, U. Saeed, V. Agarwal, S. Ramakrishnan et al.,

V. Iyengar and . Ravindranath, Activation of apoptosis signal regulating kinase 1 623 (ASK1) and translocation of death-associated protein, Daxx, in substantia 624 nigra pars compacta in a mouse model of Parkinson's disease: protection by 625 alpha-lipoic acid, FASEB J, vol.21, pp.2226-2236, 2007.

F. Ahmad, P. Nidadavolu, L. Durgadoss, and V. Ravindranath, , p.627

, Akt1 regulate its activity and proteasomal degradation: implications for 628 neurodegenerative diseases, Free Radic, Biol. Med, vol.74, 2014.

L. Brichta and P. Greengard, Molecular determinants of selective dopaminergic 631 vulnerability in Parkinson's disease: an update, Front. Neuroanat, vol.8, pp.1-632, 2014.

E. W. Kostuk, J. Cai, and L. Iacovitti, Subregional differences in astrocytes underlie 634 selective neurodegeneration or protection in Parkinson's disease models in 635 culture, Glia, vol.67, pp.1542-1557, 2019.

O. J. Lieberman, S. J. Choi, E. Kanter, A. Saverchenko, M. D. Frier et al., , p.637

M. Wu, J. Kondapalli, E. Zampese, D. J. Surmeier, D. Sulzer et al., , p.638

, Dependent Calcium Entry Underlies Differential Sensitivity of, p.639

C. Sn and . Dopaminergic, , p.640

, , pp.167-184, 2017.

P. Damier, E. C. Hirsch, P. Zhang, Y. Agid, and F. Javoy-agid, Glutathione 643 peroxidase, glial cells and Parkinson's disease, Neuroscience, vol.52, issue.93, p.90175, 1993.

T. L. Perry, D. V. Godin, and S. Hansen, Parkinson's disease: A disorder due to 646 nigral glutathione deficiency?, Neurosci. Lett, vol.33, 1982.