Cited by 382Parkinson's Disease Mechanisms and TreatmentsNeurological diseases and metabolismNuclear Receptors and Signaling

The DOI matches its Crossref record; 67 of the 68 references it cites were found in a registry or an index.

An introduction to the free radical hypothesis in Parkinson's disease

Olanow, C. W.·1992·Annals of Neurology

DOI 10.1002/ana.410320703

Open this paper in CoChat — free account

Abstract

Iron-induced oxidant stress has been implicated in the pathogenesis of Parkinson's disease. An increasing body of evidence now indicates that in Parkinson's disease the environment within the substantia nigra is conducive to the formation of cytotoxic free radicals and cell degeneration. Dopamine neurons may be particularly vulnerable because of the oxidative metabolism of dopamine and the potential of neuromelanin to promote the site-specific accumulation and reduction of iron. This hypothesis has attracted considerable attention because it opens the way for employing antioxidant strategies as possible neuroprotective treatment for Parkinson's disease. Although the concept is appealing, free radicals have not yet been proven to play a role in Parkinson's disease, and many important issues remain to be resolved before the oxidative hypothesis can ultimately be confirmed or refuted.

Integrity signals

Registry

Crossref · 10.1002/ana.410320703

Cites

67 of 67 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Superoxide Dismutase
McCord, J. M., & Fridovich, I. (1969) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)63504-5 · Cited by 12,952
Oxygen toxicity, oxygen radicals, transition metals and disease
Halliwell, B., & Gutteridge, J. M. C. (1984) · Biochemical Journal · doi:10.1042/bj2190001 · Cited by 5,330
Mitochondrial DNA and human evolution
Cann, R. L., Stoneking, M., & Wilson, A. C. (1987) · Nature · doi:10.1038/325031a0 · Cited by 3,100
Oxygen free radicals and iron in relation to biology and medicine: Some problems and concepts
Halliwell, B., & Gutteridge, J. M. C. (1986) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(86)90305-x · Cited by 2,038
DNA damage and oxygen radical toxicity
Imlay, J. A., & Linn, S. (1988) · Science · doi:10.1126/science.3287616 · Cited by 1,974
Oxygen radicals and human disease
CROSS, C. E., HALLIWELL, B., BORISH, E. T., PRYOR, W. A., AMES, B. N., SAUL, R. L., McCORD, J. M., & HARMAN, D. (1987) · Annals of Internal Medicine · doi:10.7326/0003-4819-107-4-526 · Cited by 1,856
MITOCHONDRIAL COMPLEX I DEFICIENCY IN PARKINSON'S DISEASE
Schapira, A. H. V., Cooper, J. A. D., Dexter, D. T., Jenner, P. G., Clark, J. B., & MARSDEN, C. D. (1989) · The Lancet · doi:10.1016/s0140-6736(89)92366-0 · Cited by 1,757
The effect of age on the non-haemin iron in the human brain
Hallgren, B., & Sourander, P. (1958) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1958.tb12607.x · Cited by 1,427
Basal Lipid Peroxidation in Substantia Nigra Is Increased in Parkinson's Disease
Dexter, D. T., Carter, C. J., Wells, F. R., Javoy-Agid, F., Agid, Y., Lees, A. J., Jenner, P. G., & MARSDEN, C. D. (1989) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1989.tb09133.x · Cited by 1,397
Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains
Riederer, P., Sofic, E., Rausch, W., Schmidt, B., Reynolds, G. P., Jellinger, K., & Youdim, M. B. H. (1989) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1989.tb09150.x · Cited by 1,383
Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-pyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine
Nicklas, W. J., Vyas, I. L., & Heikkila, R. E. (1985) · Life Sciences · doi:10.1016/0024-3205(85)90146-8 · Cited by 1,273
Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson's disease
Dexter, D. T., Wells, F. R., Lee, A. J., Agid, F., Agid, Y., Jenner, P., & Marsden, C. D. (1989) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1989.tb07264.x · Cited by 1,149
Abnormalities of the electron transport chain in idiopathic parkinson's disease
Parker, W. D., Boyson, S. J., & Parks, J. K. (1989) · Annals of Neurology · doi:10.1002/ana.410260606 · Cited by 1,061
Alterations in the levels of iron, ferritin and other trace metals in Parkinson's disease and other neurodegenerative diseases affecting the basal ganglia
DEXTER, D. T., CARAYON, A., JAVOY-AGID, F., AGID, Y., WELLS, F. R., DANIEL, S. E., LEES, A. J., JENNER, P., & MARSDEN, C. D. (1991) · Brain · doi:10.1093/brain/114.4.1953 · Cited by 1,043
Effect of Deprenyl on the Progression of Disability in Early Parkinson's Disease
The Parkinson Study Group* (1989) · New England Journal of Medicine · doi:10.1056/nejm198911163212004 · Cited by 912
CENTRAL CERVICAL CORD SYNDROME AFTER HEADING A FOOTBALL
Scoppetta, C., & Vaccario, M. L. (1978) · The Lancet · doi:10.1016/s0140-6736(78)92517-5 · Cited by 755
Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain
Sofic, E., Riederer, P. F., Heinsen, H., Beckmann, H., Reynolds, G. P., Hebenstreit, G. F., & Youdim, M. B. H. (1988) · Journal of Neural Transmission · doi:10.1007/bf01244786 · Cited by 754
Parkinson's disease: A disorder due to nigral glutathione deficiency?
Perry, T. L., Godin, D. V., & Hansen, S. (1982) · Neuroscience Letters · doi:10.1016/0304-3940(82)90390-1 · Cited by 753
Deficiencies in Complex I subunits of the respiratory chain in Parkinson's disease
Mizuno, Y., Ohta, S., Tanaka, M., Takamiya, S., Suzuki, K., SATO, T. A., Oya, H., Ozawa, T., & Kagawa, Y. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)91141-8 · Cited by 735
The Effect of Deprenyl (Selegiline) on the Natural History of Parkinson's Disease
Tetrud, J. W., & Langston, J. W. (1989) · Science · doi:10.1126/science.2502843 · Cited by 635
Free radicals, lipids and protein degradation
Wolff, S. P., Garner, A., & Dean, R. T. (1986) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(86)90228-8 · Cited by 551
Receptor‐mediated transcytosis of transferrin across the blood‐brain barrier
Fishman, J. B., Rubin, J. B., Handrahan, J. V., Connor, J. R., & Fine, R. E. (1987) · Journal of Neuroscience Research · doi:10.1002/jnr.490180206 · Cited by 550
Iron and aluminum increase in the substantia nigra of patients with Parkinson's disease: an X-ray microanalysis
Hirsch, E. C., Brandel, J. ‐., Galle, P., Javoy‐Agid, F., & Agid, Y. (1991) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1991.tb08170.x · Cited by 537
The regional distribution and cellular localization of iron in the rat brain
Hill, J. M., & Switzer, R. C. (1984) · Neuroscience · doi:10.1016/0306-4522(84)90046-0 · Cited by 486
Cellular distribution of transferrin, ferritin, and iron in normal and aged human brains
Connor, J. R., Menzies, S. L., Martin, S. M. S., & Mufson, E. J. (1990) · Journal of Neuroscience Research · doi:10.1002/jnr.490270421 · Cited by 472
Oxidants and the central nervous system: some fundamental questions. Is oxidant damage relevant to Parkinson's disease, Alzheimer's disease, traumatic injury or stroke?
Halliwell, B. B. (1989) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.1989.tb01779.x · Cited by 468
A Selective Increase in Particulate Superoxide Dismutase Activity in Parkinsonian Substantia Nigra
Saggu, H. K., Cooksey, J., Dexter, D. T., Wells, F. R., Lees, A. J., Jenner, P. G., & MARSDEN, C. D. (1989) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1989.tb11759.x · Cited by 454
Brain iron and ferritin in Parkinson’s and Alzheimer’s diseases
Jellinger, K., Paulus, W., Grundke-Iqbal, I., Riederer, P., & Youdim, M. B. H. (1990) · Journal of Neural Transmission - Parkinson's Disease and Dementia Section · doi:10.1007/bf02252926 · Cited by 445
Brain Peroxidase and Catalase in Parkinson Disease
Ambani, L. M., Woert, M. H. V., & Murphy, S. (1975) · Archives of Neurology · doi:10.1001/archneur.1975.00490440064010 · Cited by 404
Dopamine turnover and glutathione oxidation: implications for Parkinson disease.
Spina, M. B., & Cohen, G. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.4.1398 · Cited by 397
Protection against tissue damage in vivo by desferrioxamine: What is its mechanism of action?
Halliwell, B. B. (1989) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(89)90145-7 · Cited by 378
Increase of deleted mitochondrial DNA in the striatum in Parkinson's disease and senescence
Ikebe, S.-I., Tanaka, M., Ohno, K., Sato, W., Hattori, K., Kondo, T., Mizuno, Y., & Ozawa, T. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)90497-b · Cited by 341
Toxicity of 6‐hydroxydopamine and dopamine for dopaminergic neurons in culture
Michel, P. P., & Hefti, F. F. (1990) · Journal of Neuroscience Research · doi:10.1002/jnr.490260405 · Cited by 339
Mitochondrial oxidative phosphorylation defects in parkinson's disease
Shoffner, J. M., Watts, R. L., Juncos, J. L., Torroni, A., & Wallace, D. C. (1991) · Annals of Neurology · doi:10.1002/ana.410300304 · Cited by 333
Glutathione peroxidase activity in Parkinson's disease brain
Kish, S. J., Morito, C. L. H., & Hornykiewicz, O. (1985) · Neuroscience Letters · doi:10.1016/0304-3940(85)90078-3 · Cited by 303
The Iron Chelator Desferrioxamine (Desferal) Retards 6‐Hydroxydopamine‐Induced Degeneration of Nigrostriatal Dopamine Neurons
Ben‐Shachar, D., Eshel, G., Finberg, J. P. M., & Youdim, M. B. H. (1991) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1991.tb11444.x · Cited by 299
Is Parkinson's disease a progressive siderosis of substantia nigra resulting in iron and melanin induced neurodegeneration?
Youdim, M. B. H., Ben‐Shachar, D., & Riederer, P. F. (1989) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.1989.tb01782.x · Cited by 292
The role of iron in the initiation of lipid peroxidation
Minotti, G., & Aust, S. D. (1987) · Chemistry and Physics of Lipids · doi:10.1016/0009-3084(87)90050-8 · Cited by 272
Decreased ferritin levels in brain in Parkinson's disease
Dexter, D. T., Carayon, A., Vidailhet, M., Ruberg, M., Agid, F., Agid, Y., Lees, A. J., Wells, F. R., Jenner, P., & Marsden, C. D. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb08814.x · Cited by 258
Oxygen Radicals and Tissue Injury
(1997) · Inflammation Research · doi:10.1007/bf03354123 · Cited by 257
Evidence for a defect in NADH
Parker, W. D., Boyson, S. J., LUDER, A. S., & Parks, J. K. (1990) · Neurology · doi:10.1212/wnl.40.8.1231 · Cited by 230
Studies on Parkinson's Disease Including X-Ray Fluorescent Spectroscopy of Formalin Fixed Brain Tissue
Earle, K. M. (1968) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-196801000-00001 · Cited by 227
Excitatory Amino Acid Release from Rat Hippocampal Slices as a Consequence of Free‐Radical Formation
Pellegrini-Giampietro, D. E., Cherici, G., Alesiani, M., Carlà, V., & Moroni, F. (1988) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1988.tb01187.x · Cited by 206
Intranigral Iron Injection Induces Behavioral and Biochemical “Parkinsonism” in Rats
Ben‐Shachar, D., & Youdim, M. B. H. (1991) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1991.tb06432.x · Cited by 197
Chronic dietary pergolide preserves nigrostriatal neuronal integrity in aged-Fischer-344 rats
Felten, D. L., Felten, S. Y., Fuller, R. W., Romano, T. D., Smalstig, E. B., Wong, D. T., & Clemens, J. A. (1992) · Neurobiology of Aging · doi:10.1016/0197-4580(92)90048-3 · Cited by 150
Effect of age at onset on progression and mortality in Parkinson's disease
Diamond, S. G., Markham, C. H., Hoehn, M. M. M., MCDOWELL, F. H., & Muenter, M. D. (1989) · Neurology · doi:10.1212/wnl.39.9.1187 · Cited by 141
Dopamine depletion protects striatal neurons from ischemia-induced cell death
Clemens, J. A., & Phebus, L. A. (1988) · Life Sciences · doi:10.1016/0024-3205(88)90463-8 · Cited by 140
The effect of melanin on iron associated decomposition of hydrogen peroxide
Pilas, B., Sarna, T., Kalyanaraman, B., & Swartz, H. M. (1988) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(88)90049-4 · Cited by 139
Preservation of the substanitia nigra and locus coeruleus in a patient receiving levodopa (2 kg) plus decarboxylase inhibitor over a four‐year period
Quinn, N. P., Parkes, D., Janota, I., & MARSDEN, C. D. (1986) · Movement Disorders · doi:10.1002/mds.870010109 · Cited by 132
Scientific Basis for the Treatment of Parkinson??s Disease
Wolters, E. C. (2006) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-200607000-00011 · Cited by 131
Nigrostriatal Dopaminergic Neurons Remain Undamaged in Rats Given High Doses of l ‐DOPA and Carbidopa Chronically
Perry, T. L., Yong, V. W., Ito, M., Foulks, J. G., Wall, R. A., Godin, D. V., & Clavier, R. M. (1984) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1984.tb12834.x · Cited by 130
Long‐term administration of L‐DOPA does not damage dopaminergic neurons in the mouse
Hefti, F. F., Melamed, E., Bhawan, J., & Wurtman, R. J. (1981) · Neurology · doi:10.1212/wnl.31.9.1194 · Cited by 126
Hemoglobin-mediated oxidant damage to the central nervous system requires endogenous ascorbate.
Sadrzadeh, S. M. H., & Eaton, J. W. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113759 · Cited by 124
Imaging of the aging brain. Part II. Pathologic conditions.
Drayer, B. P. (1988) · Radiology · doi:10.1148/radiology.166.3.3277248 · Cited by 117
Parkinsonism and Aging, 1989
Fishman, L. M. (1990) · Topics in Geriatric Rehabilitation · doi:10.1097/00013614-199004000-00018 · Cited by 114
Effect of ferritin-containing fractions with different iron loading on lipid peroxidation
Gutteridge, J. M. C., Halliwell, B. B., Treffry, A., Harrison, P. M., & Blake, D. R. (1983) · Biochemical Journal · doi:10.1042/bj2090557 · Cited by 113
Mitochondrial DNA analysis in Parkinson's disease
Schapira, A. H. V., Holt, I. J., Sweeney, M. G., Harding, A. E., Jenner, P. G., & MARSDEN, C. D. (1990) · Movement Disorders · doi:10.1002/mds.870050406 · Cited by 112
Combined bromocriptine‐levodopa therapy early in Parkinson's disease
Rinne, U. K. (1985) · Neurology · doi:10.1212/wnl.35.8.1196 · Cited by 111
Iron chelation prevents tissue injury following ischemia
Aust, S. D., & White, B. C. (1985) · Advances in free radical biology and medicine · doi:10.1016/8755-9668(85)90003-1 · Cited by 109
Glutathione in Parkinson's disease: A link between oxidative stress and mitochondrial damage?
Monte, D. A. D., Chan, P., & Sandy, M. S. (1992) · Annals of Neurology · doi:10.1002/ana.410320719 · Cited by 107
Iron induces degeneration of nigrostriatal neurons
Sengstock, G. J., Olanow, C. W., Dunn, A. J., & Arendash, G. W. (1992) · Brain Research Bulletin · doi:10.1016/0361-9230(92)90118-h · Cited by 90
Self-citation
Exposure of striatal [corrected] synaptosomes to L-dopa increases levels of oxidized glutathione.
Spina, M. B., & Cohen, G. (1988) · PubMed · Cited by 77
Modulation by neuromelanin of the availability and reactivity of metal ions
Swartz, H. M., Sarna, T., & Zecca, L. (1992) · Annals of Neurology · doi:10.1002/ana.410320712 · Cited by 73
Does selegiline monotherapy in Parkinson's disease act by symptomatic or protective mechanisms?
Olanow, C. W., & Calne, D. B. (1992) · PubMed · Cited by 59
Self-citation
A Rationale for Dopamine Agonists as Primary Therapy for Parkinson’s Disease
Olanow, C. W. (1992) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100041469 · Cited by 54
Self-citation
Central Mechanisms and Levodopa Response Fluctuations in Parkinsonʼs Disease
Mouradian, M. M., & Chase, T. N. (1988) · Clinical Neuropharmacology · doi:10.1097/00002826-198808000-00007 · Cited by 48
IN PRAISE OF PEROXIDATION
Dormandy, T. L. (1988) · The Lancet · doi:10.1016/s0140-6736(88)90535-1 · Cited by 31

Flagged first, then by citations

1 of the 68 references couldn’t be matched to a known paper.

Research works printed but not linked: 14

Halliwell, 1985, TINS, 8, 22
Cohen, 1990, Neural Transm, 32, 229
Olanow, 1990, Neurology, 40, 32
Halliwell, 1988, ISI Atlas Sci Biochem, 1, 48
Potts, 1976, Exp Eye Res, 48, 221
Sarna, 1976, Science, 1132, 192
Brain iron: MRI studies in Parkinson's syndrome. In: eds. Florham Park, New Jersey: MacMillan Healthcare, 1987: 135-143
Sengstock, 1991, Movement Dis, 6, 272
Olanow, 1991, Neurology, 42, 13
Riederer, 1989, J Neurochem, 52, 515, 10.1111/j.1471-4159.1989.tb09150.x · DOI · Paper page
Good, 1992, J Neuropathol Exp Neurol, 51, 327
et al. Vitamin E levels in brain are not altered in Parkinson's disease. Ann Neurol 1992 (in press)
et al. Brain skeletal muscle and platelet mitochondrial function in Parkinson's disease. Brain 1992 (in press)
Spina, 1988, J Pharmacol Exp Ther, 247, 502

Sorted by citations

Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis
Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O'Regan, J. P., Deng, H.-X., et al. (1993) · Nature · doi:10.1038/362059a0 · Cited by 7,062
Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader11Mention of a trade name, proprietary product, or specific equipment does not constitute a guarantee by the United States Department of Agriculture and does not imply its approval to the exclusion of other products that may be suitable.
Wang, H., & Joseph, J. A. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00107-0 · Cited by 2,355
Hydrogen peroxide mediates amyloid β protein toxicity
Behl, C. (1994) · Cell · doi:10.1016/0092-8674(94)90131-7 · Cited by 2,074
Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen
Braak, H., R�b, U., Gai, W. P., & Del Tredici, K. (2003) · Journal of Neural Transmission · doi:10.1007/s00702-002-0808-2 · Cited by 1,683
Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease
Jack, C. R., Petersen, R. C., Xu, Y. C., Waring, S. C., O'Brien, P. C., Tangalos, E. G., Smith, G. E., Ivnik, R. J., & Kokmen, E. (1997) · Neurology · doi:10.1212/wnl.49.3.786 · Cited by 1,128

See all 382

Authors: Olanow, C. W.
Affiliations: University of South Florida (US)
Corresponding author: Olanow, C. W.
ORCID: Olanow, C. W.
Venue: Annals of Neurology
Publisher: Wiley
Published: 1992
Volume: 32
Issue: S1
Pages: S2-S9
ISSN: 0364-5134 (ISSN-L)
1531-8249
DOI: 10.1002/ana.410320703
OpenAlex: W2156259977
Cited by: 382
References: 68
Citations by year: 2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 6 · 2016: 7 · 2015: 2 · 2014: 6 · 2013: 5 · 2012: 13
FWCI: 3.32
Type: journal article
Language: en
Open access: closed
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 8644 d)
Locations: Annals of Neurology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Keywords: Parkinson's disease, oxidative stress, iron accumulation, substantia nigra, dopaminergic neurons, neuromelanin, dopamine oxidation, neuroprotection, antioxidants, neurodegeneration
MeSH terms: Animals, Free Radicals, Humans, Iron, Parkinson Disease, Substantia Nigra, Lipid Peroxidation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

An introduction to the free radical hypothesis in Parkinson's disease

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks