The DOI matches its Crossref record; 77 of the 77 references it cites were found in a registry or an index.
Clinical progression in Parkinson disease and the neurobiology of axons
Open accessAbstract
Despite tremendous growth in recent years in our knowledge of the molecular basis of Parkinson disease (PD) and the molecular pathways of cell injury and death, we remain without therapies that forestall disease progression. Although there are many possible explanations for this lack of success, one is that experimental therapeutics to date have not adequately focused on an important component of the disease process, that of axon degeneration. It remains unknown what neuronal compartment, either the soma or the axon, is involved at disease onset, although some have proposed that it is the axons and their terminals that take the initial brunt of injury. Nevertheless, this concept has not been formally incorporated into many of the current theories of disease pathogenesis, and it has not achieved a wide consensus. More importantly, in view of growing evidence that the molecular mechanisms of axon degeneration are separate and distinct from the canonical pathways of programmed cell death that mediate soma destruction, the possibility of early involvement of axons in PD has not been adequately emphasized as a rationale to explore the neurobiology of axons for novel therapeutic targets. We propose that ongoing degeneration of axons, not cell bodies, is the primary determinant of clinically apparent progression of disease, and that future experimental therapeutics intended to forestall disease progression will benefit from a new focus on the distinct mechanisms of axon degeneration.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The cited source doesn’t support the claim as written.
In the citing paper
“The diagnosis of PD is reliant on clinical motor symptoms and neuroimaging; however, by the onset of symptoms, it is estimated that 50–70% of substantia nigra pars compacta dopaminergic neurons have already been lost [247, 248].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [247]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
RETRACTED ARTICLE: APP binds DR6 to trigger axon pruning and neuron death via distinct caspases
Nikolaev, A., McLaughlin, T., O’Leary, D. D. M., & Tessier-Lavigne, M. (2009) · Nature · doi:10.1038/nature07767 · Cited by 992
RetractedStaging of brain pathology related to sporadic Parkinson’s disease
Braak, H., Tredici, K. D., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00065-9 · Cited by 10,777 · cited 1×
“It has been proposed that PD begins in the regions of the dorsal motor nucleus of the vagus and the olfactory bulb.(14) However, this proposal has been controversial and does not relate directly to the question of the initial events at the cellular level.”
BackgroundSpillantini, M. G., Schmidt, M. L., Lee, V. M.-Y., Trojanowski, J. Q., Jakes, R., & Goedert, M. (1997) · Nature · doi:10.1038/42166 · Cited by 8,382 · cited 4×
“The impact was further amplified when it was discovered that -synuclein protein is a major component of LB.36 With the development of sensitive antibodies to -synuclein, it has become easier to detect LB in tissue sections, and they have become a great focus of attention.”
BackgroundInfluentialDauer, W., & Przedborski, S. (2003) · Neuron · doi:10.1016/s0896-6273(03)00568-3 · Cited by 5,469
AGEING AND PARKINSON'S DISEASE: SUBSTANTIA NIGRA REGIONAL SELECTIVITY
FEARNLEY, J. M., & LEES, A. J. (1991) · Brain · doi:10.1093/brain/114.5.2283 · Cited by 3,529
Bernheimer, H., Birkmayer, W., Hornykiewicz, O., Jellinger, K. A., & SEITELBERGER, F. (1973) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(73)90175-5 · Cited by 2,650 · cited 2×
“(A) A graphical representation of the data presented in the oft-cited Bernheimer et al study to support the statement that there is an 80% reduction at the time of disease onset.(26) In the Bernheimer study, only 13 brains from patients with a diagnosis of Parkinson disease (PD) were subjected to biochemical analysis.”
BackgroundMethodMechanisms And Functions Of Cell Death
Ellis, R. E., Yuan, J., & Horvitz, H. R. (1991) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.07.110191.003311 · Cited by 2,088
Lang, A. E., & Lozano, A. M. (1998) · New England Journal of Medicine · doi:10.1056/nejm199810083391506 · Cited by 2,072
Reversal of experimental parkinsonism by lesions of the subthalamic nucleus.
Bergman, H., Wichmann, T., & Delong, M. (1990) · Science · doi:10.1126/science.2402638 · Cited by 2,003 · cited 1×
“Such was the case for the discovery of L-dopa, and more recently for the discovery that deep brain stimulation is an effective adjunctive treatment.(1,2) Despite these important advances, we remain unable to offer therapies that halt the progression of the disease, and in this crucial respect therapies for PD are as l…”
BackgroundUneven Pattern of Dopamine Loss in the Striatum of Patients with Idiopathic Parkinson's Disease
Kish, S. J., Shannak, K. S., & Hornykiewicz, O. (1988) · New England Journal of Medicine · doi:10.1056/nejm198804073181402 · Cited by 1,945 · cited 1×
“ing on disease duration, although there has been 60 to 80% loss of SN dopamine neurons,(23,33) there has been a much more profound loss of striatal or putaminal dopaminergic markers.(26,28,29) It may still be argued that it is difficult to make comparisons in these data, due to dif-”
Background
Research works printed but not linked: 4
- Agid Y, 1987, Movement disorders 2, 166
- Dodiya HB, 2009, The status of dopaminergic putaminal innervation in Parkinson's disease as a function of disease duration: relevance to trophic factor therapy, Abstr Soc Neurosci
- Cheng HC, 2008, Akt/PKB inhibits retrograde axonal degeneration in the nigro‐striatal dopaminergic pathway in vivo, Abstr Soc Neurosci
- Chen X, 2008, Restoration of the nigrostriatal dopaminergic pathway in mouse models of Parkinson's disease: effects of a constitutively active form of AKT, Abstr Soc Neurosci
Cited by
Sorted by citations
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286
Hallmarks of neurodegenerative diseases
Wilson, D. M., Cookson, M. R., Van Den Bosch, L., Zetterberg, H., Holtzman, D. M., & Dewachter, I. (2023) · Cell · doi:10.1016/j.cell.2022.12.032 · Cited by 1,789
Dopamine: Functions, Signaling, and Association with Neurological Diseases
Klein, M. O., Battagello, D. S., Cardoso, A. R., Hauser, D. N., Bittencourt, J. C., & Correa, R. G. (2019) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-018-0632-3 · Cited by 1,073
Brain-first versus body-first Parkinson’s disease: a multimodal imaging case-control study
Horsager, J., Andersen, K. B., Knudsen, K., Skjærbæk, C., Fedorova, T. D., Okkels, N., Schaeffer, E., Bonkat, S. K., Geday, J., Otto, M., et al. (2020) · Brain · doi:10.1093/brain/awaa238 · Cited by 782
Oxidative stress in the aging substantia nigra and the etiology of Parkinson's disease
Trist, B. G., Hare, D. J., & Double, K. L. (2019) · Aging Cell · doi:10.1111/acel.13031 · Cited by 778
Metadata
- Authors
- Cheng, H., Ulane, C. M., & Burke, R. E.
- Affiliations
- Columbia University Irving Medical Center (US)
- Corresponding author
- Burke, Robert E.
- ORCID
- Burke, Robert E.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2010-05-26
- Volume
- 67
- Issue
- 6
- Pages
- 715-725
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC2918373
- OpenAlex
- W1967659552
- Cited by
- 1,012
- References
- 77
- Citations by year
- 2026: 56 · 2025: 74 · 2024: 101 · 2023: 92 · 2022: 108 · 2021: 109 · 2020: 100 · 2019: 82 · 2018: 67 · 2017: 59 · 2016: 35 · 2015: 36 · 2014: 24 · 2013: 22 · 2012: 23
- FWCI
- 12.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS26836, P50NS038370, R56NS026836, NS38370, R01NS026836)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- Parkinson's disease, axonal degeneration, disease progression, axonal injury, programmed cell death, therapeutic target, pathogenesis, axon terminals
- MeSH terms
- Axons, Humans, Neurobiology, Neurons, Parkinson Disease, Disease Progression
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
