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
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“This observation is in agreement with a similar analysis that was performed on autopsy specimens ([51](#R51)).”
From Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease (1997) · cites this paper as [51]
Citations
Cites
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
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
Cited by
Sorted by citations
Items 301–381 of 381
An Overview of Novel Therapies for Parkinson's Disease
Fahn, S. (1997) · Experimental Neurology · doi:10.1006/exnr.1996.6382 · Cited by 7
Ropinirole in the treatment of Parkinson’s disease
Zesiewicz, T., & Hauser, R. A. (1999) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.8.5.697 · Cited by 7
Cohadon, F. (1994) · Advances and technical standards in neurosurgery · doi:10.1007/978-3-7091-6648-2_3 · Cited by 7
The role of lamotrigine in the treatment of epilepsy
Leppik, I. E. (1998) · Neurology · doi:10.1212/wnl.51.4.940 · Cited by 7
Iron storage and transport markers in Parkinson’s disease and MPTP-treated mice
Mash, D. C., Singer, J. T., Pablo, J. P., Basile, M. J., Bruce, J. H., & Weiner, W. J. (1993) · Key topics in brain research · doi:10.1007/978-3-7091-9322-8_9 · Cited by 6
Indicators of Oxidative Stress in Aged Fischer 344 Rats: Potential for Neurotrophic Treatment
Williams, L. R., Carter, D. B., Dunn, E., & Connor, J. R. (1995) · Advances in behavioral biology · doi:10.1007/978-1-4757-9145-7_92 · Cited by 6
Localization of a new ferritin heavy chain sequence present in human brain mRNA to chromosome 11
Percy, M. E., Bauer, S. J., Rainey, S., McLachlan, D. R. C., Dhar, M. S., & Joshi, J. G. (1995) · Genome · doi:10.1139/g95-059 · Cited by 6
Hely, M. A., Morris, J. G., Burns, R. J., Lander, C. M., McLaughlin, D. B., & Donnan, G. A. (1996) · Journal of Clinical Neuroscience · doi:10.1016/s0967-5868(96)90056-9 · Cited by 6
Khan, H. A. (2004) · Inflammopharmacology · doi:10.1163/156856004773121392 · Cited by 5
Neuroprotective Strategies in Neural Grafting
Brundin, P., & Schierle, G. S. K. (2000) · Neuromethods · doi:10.1007/978-1-59259-690-4_19 · Cited by 5
Yantiri, F., Gasparyan, A., & Andersen, J. K. (2001) · Journal of Neuroscience Research · doi:10.1002/jnr.1066 · Cited by 5
Extracellular ATP May Induce Neuronal Degeneration by a Free‐radical Mechanisma
CHENG, Y., Chen, M., Wixom, P., & Sun, A. Y. (1994) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1994.tb21834.x · Cited by 5
., P., Naraboli, B. S., & Biradar, J. S. (2017) · International Journal of Pharmacy and Pharmaceutical Sciences · doi:10.22159/ijpps.2017v9i10.21083 · Cited by 4
Oxidative Stress and Excitatory Neurotoxins in Neuropathy
Low, P. A. (2005) · Elsevier eBooks · doi:10.1016/b978-0-7216-9491-7.50026-0 · Cited by 4
Waladkhani, A. R., & Hellhammer, D. H. (2008) · Advances in clinical chemistry · doi:10.1016/s0065-2423(07)00005-4 · Cited by 5
Medical Treatment of Parkinson Disease
Fahn, S., Jankovic, J. J., Hallett, M., & Jenner, P. G. (2007) · Elsevier eBooks · doi:10.1016/b978-0-443-07941-2.50009-7 · Cited by 4
Clinical trials of promising apoptosis modulating drugs
Sharma, N., Kumari, R. M., Arya, G., Gupta, N., Chandra, R., & Nimesh, S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-815762-6.00010-x · Cited by 4
Shie, F., & Ling, Z. (2007) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.17.4.419 · Cited by 4
MPP+ and glutamate in the degeneration of nigral dopaminergic neurons
Sawada, H., & Shimohama, S. (1999) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(99)00039-5 · Cited by 4
Management of Parkinson Disease
Murdoch, D. R., Cheer, S. M., & Wagstaff, A. J. (2004) · Disease Management & Health Outcomes · doi:10.2165/00115677-200412010-00004 · Cited by 4
(2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.1993.tb03114.x · Cited by 4
New Therapeutic Approaches: Rationale and Results
Mitsumoto, H. (1995) · Springer eBooks · doi:10.1007/978-1-4471-1871-8_18 · Cited by 4
Retracted: Mitochondria, the missing link between body and soul: Proteomic prospective evidence
Warda, M., & Han, J. (2008) · PROTEOMICS · doi:10.1002/pmic.200700695 · Cited by 3
RetractedMelatonin in Parkinson’s Disease and Its Therapeutic Potential
Srinivasan, V., Srinivasan, U. S., Kaur, C., Zakaria, R., Othman, Z., Lauterbach, E. C., & Acuña-Castroviejo, D. (2013) · Springer eBooks · doi:10.1007/978-81-322-0825-9_17 · Cited by 3
Nuclear microscopy in the life sciences at the national university of singapore
Ren, M., Thong, P. S. P., Makjanić, J., Ponraj, D., & Watt, F. (1999) · Biological Trace Element Research · doi:10.1007/bf02784192 · Cited by 3
Oxidative Stress in Parkinson’s Disease
Ceballos-Picot, I. (1997) · Neuroscience intelligence unit · doi:10.1007/978-3-662-22516-5_8 · Cited by 3
Ryu, J.-S., Do, J., Kang, H., & Lee, J. K. (2021) · Neurochemical Journal · doi:10.1134/s1819712421010104 · Cited by 3
Oxidative Stress with Emphasis on the Role of LAMMA in Parkinson’s Disease
Good, P. F., Perl, D. P., & Olanow, C. W. (1997) · Springer eBooks · doi:10.1007/978-1-4899-0197-2_14 · Cited by 3
Self-citationNitric Oxide and Oxidative Damage in the CNS
Dawson, D. A. (1997) · Springer eBooks · doi:10.1007/978-1-4899-0197-2_11 · Cited by 3
Liu, G., Men, P., Perry, G. L., & Smith, M. A. (2003) · Wiley eBooks · doi:10.1002/9783527610419.ntls0122 · Cited by 3
Majumdar, R., Cwik, V. A., & Brooke, M. H. (1994) · Neuromuscular Disorders · doi:10.1016/0960-8966(94)90088-4 · Cited by 3
Neurodegenerative Disease and Oxidative Stress: Insights from an Animal Model of Parkinsonism
Hastings, T. G., & Zigmond, M. J. (1996) · Springer eBooks · doi:10.1007/978-1-4899-0209-2_6 · Cited by 2
Indices of Oxidative Stress in the Peripheral Blood of De Novo Patients With Parkinson’s Disease
Ilic, T. V., Jovanović, M., Jovicic, A., & Tomovic, M. (1998) · Advances in behavioral biology · doi:10.1007/978-1-4615-5337-3_111 · Cited by 2
Physiology and pathophysiology of basalganglia: Impact on motor system function
Weicker, H., Kinscherf, R., Diserens, K., Deigner, H., & Strüder, H. K. (2001) · European Journal of Sport Science · doi:10.1080/17461390100071209 · Cited by 2
Nuclear microscopy in Parkinson's disease
Watt, F., Lee, T., Thong, P. S. P., & Tang, S. M. (1995) · Nuclear Instruments and Methods in Physics Research Section B Beam Interactions with Materials and Atoms · doi:10.1016/0168-583x(95)00455-6 · Cited by 2
Fox, C. M., Drost, M., & Mueller, S. (2007) · DOAJ (DOAJ: Directory of Open Access Journals) · Cited by 2
Joseph, J. A., Denisova, N., Fisher, D., Cantuti‐Castelvetri, I., & Erat, S. (1998) · Advances in behavioral biology · doi:10.1007/978-1-4615-5337-3_9 · Cited by 2
Advances in the Understanding of the Cause of Parkinson's Disease
Schapira, A. H. V. (1994) · Journal of the Royal Society of Medicine · doi:10.1177/014107689408700701 · Cited by 2
Fischer, R. (2011) · OPUS Publication Server of the University of Stuttgart (University of Stuttgart) · doi:10.18419/opus-1905 · Cited by 2
Gheybi, E., Jalili‐Nik, M., Hosseinzadeh, P., Mirzaei, S. M., Alalikhan, A., & Soukhtanloo, M. (2026) · BMC Neuroscience · doi:10.1186/s12868-025-00991-3 · Cited by 1
Nutrients and Food Constituents in Cognitive Decline and Neurodegenerative Disease
Joseph, J. A., Casadesús, G., Smith, M. A., Perry, G. L., & Shukitt‐Hale, B. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-391884-0.00020-2 · Cited by 1
Aging with Parkinson’s Disease
Nocera, J. R., & McGregor, K. (2018) · Handbooks in health, work, and disability · doi:10.1007/978-3-030-03916-5_8 · Cited by 1
Mitochondrial DNA as a Factor of Glaucomous Optic Neuropathy’s Development Mechanism
Газизова, И. Р., Mazunin, I., Malishevskaya, Т. N., Киселева, О. А., Gadzhiev, A. M., & Rindzhibal, A.-M. (2019) · Ophthalmology in Russia · doi:10.18008/1816-5095-2019-4-479-486 · Cited by 1
Koodalingam, A., Rajalakshmi, A., & Parthiban, E. (2021) · Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry · doi:10.2174/1871523019999210104203252 · Cited by 1
Therapeutical Implications of Melatonin in Alzheimer’s and Parkinson’s Diseases
Cardinali, D. P., Vigo, D. E., Olivar, N., Vidal, M. F., & Brusco, L. I. (2015) · Molecular and integrative toxicology · doi:10.1007/978-3-319-15630-9_9 · Cited by 1
Lallemantia canescens (L) Fisch & Mey bitkisinin ve kallus doku kültürünün antioksidan aktivitesi
Başak, S. Ş., & Candan, F. (2009) · Cited by 1
Xeroderma Pigmentosum and the DNA Damage Response to Ultraviolet Light
Cleaver, J. E. (2016) · Springer eBooks · doi:10.1007/978-1-59745-458-2_24 · Cited by 1
Medicinal Chemistry and Brain Drug Penetrance
Hilaire, J. R., & Gendelman, H. E. (2016) · Springer eBooks · doi:10.1007/978-3-319-44022-4_49 · Cited by 1
Dopamine Oxidation and Parkinson’s Disease
Barrett, C. W., Bucher, M. L., & Hastings, T. G. (2017) · Royal Society of Chemistry eBooks · doi:10.1039/9781782622888-00116 · Cited by 1
Joseph, J. A., Shukitt‐Hale, B., & Willis, L. (2010) · Wiley eBooks · doi:10.1002/9781444323375.ch12 · Cited by 1
Liehr, J. G. (1996) · Neurobiology of Aging · doi:10.1016/0197-4580(06)00018-2 · Cited by 1
Kurup, R. K., & Kurup, P. A. (2003) · International Journal of Neuroscience · doi:10.1080/00207450390220312 · Cited by 1
Modulatory Role of Terminalia chebula on Erythrocyte Defenses in Young and Aged Rats
Mahesh, R., & Begum, V. H. (2007) · Journal of Pharmacology and Toxicology · doi:10.3923/jpt.2007.709.717 · Cited by 1
Elmabruk, A. S. M. (2018) · Human Biology · Cited by 1
Paulus, W. (1995) · Springer eBooks · doi:10.1007/978-3-642-85179-7_13 · Cited by 1
Braak, H., & Tredici, K. D. (2005) · Humana Press eBooks · doi:10.1007/978-1-59259-852-6_20 · Cited by 1
Beneficial Effects of Dried Berry Fruits in Human Health and Disease Prevention
Zafra‐Stone, S., Bagchi, M., & Bagchi, D. (2013) · doi:10.1002/9781118464663.ch10
Nutritional Antioxidants, Vitamins, Cognition, and Neurodegenerative Disease
Martín, A., Smith, M. A., Perry, G. L., & Joseph, J. A. (2004) · Principles of Gender-Specific Medicine · doi:10.1016/b978-012440905-7/50345-5
Chapter 3.2.2 Adenovirus vectors for gene transfer into the central nervous system
Barkats, M., Corti, O., & Mallet, J. J. (1999) · Techniques in the behavioral and neural sciences · doi:10.1016/s0921-0709(99)80034-0
Avaliação da expressão de genes processadores de danos oxidativos em pacientes com Alzheimer
de Oliveira, D. V. N. P. (2007) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.17.2007.tde-17042009-152311
Casadesús, G., Shukitt‐Hale, B., Smith, M. A., Stellwagen, H. M., & Joseph, J. A. (2002) · Springer eBooks · doi:10.1007/978-1-4615-1067-3_6
MICROPIXE INVESTIGATIONS: TIME SEQUENCING STUDIES IN DEGENERATIVE DISEASES
Watt, F., Ren, M., & Thong, P. S. P. (1999) · International Journal of PIXE · doi:10.1142/s0129083599000292
Beskytter røyking mot Parkinsons sykdom
Flaten, T. P. (2009) · Norsk Epidemiologi · doi:10.5324/nje.v5i2.261
Joseph, J. A., Shukitt‐Hale, B., & Casadesús, G. (2005)
Pathological Changes in Neurodegenerative Disease
Mann, D. M. A. (1997) · Springer eBooks · doi:10.1007/978-1-4615-6001-2_3
protein, and DNA in the brain of rats
Liu, J., Wang, X., Shigenaga, M. K., Yeo, H. C. H., Mori, A., & Ames, B. N. (1996)
Joseph, J. A., Shukitt‐Hale, B., & Casadesús, G. (2006) · Humana Press eBooks · doi:10.1385/1-59259-952-4:067
Gabriele, J. P., Groleau, S. E., Daya, R. P., Pristupa, Z. B., & Mishra, R. K. (2012) · Springer eBooks · doi:10.1007/978-94-007-3027-4_12
Muralidhar, L. H. (2005) · CFTRI Institutional Repository
Joseph, J. A., Shukitt‐Hale, B., & Willis, L. (2009) · Oxidative stress and disease · doi:10.1201/9781420073522.ch13
Ischemic Neuronal Death in the Fish Retina
Kato, S., Zhou, Z., Sugawara, K., Yasui, Y., Takizawa, N., Sugitani, K., & Mawatari, K. (1997) · Springer eBooks · doi:10.1007/978-1-4615-5933-7_23
The Misfolding Pathway of SOD1: Implications for Drug Design in ALS
Ip, P. (2017) · TSpace (University of Toronto)
Medical treatment of Parkinson disease
Fahn, S., Jankovic, J. J., & Hallett, M. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4377-2369-4.00006-8
Deutch, A. Y., Grobin, A. C., & Dannies, P. S. (1994) · Elsevier eBooks · doi:10.1016/b978-0-08-042276-3.50032-x
Apoptosis, Glial Cells and Parkinson’s Disease
Hirsch, É. C. (2001) · Research and perspectives in neurosciences · doi:10.1007/978-3-662-04333-2_9
Mann, D. M. A. (1997) · Springer eBooks · doi:10.1007/978-1-4615-6001-2_4
(1995) · Elsevier eBooks · doi:10.1016/b978-012165250-0/50023-4
Iacono, R. P. (2005) · Van Nostrand's Scientific Encyclopedia · doi:10.1002/0471743984.vse5375
In Memoriam – Charles Warren Olanow, MD
Kieburtz, K. D., & Vickrey, B. G. (2025) · Annals of Neurology · doi:10.1002/ana.27187
Bridging Regenerative and Restorative Stem Cell Therapies in Parkinson’s Disease
Onuigbo, C. C., Martínez-Lemus, J. D., Tharp, E., & Schiess, M. C. (2026) · Cells · doi:10.3390/cells15070578
Metadata
- 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
- 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
- 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