Cited by 1,012Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNerve injury and regeneration

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Clinical progression in Parkinson disease and the neurobiology of axons

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Cheng, Hsiao‐Chun, Ulane, Christina M., Burke, Robert E.·2010·Annals of Neurology

DOI 10.1002/ana.21995PMC PMC2918373

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Abstract

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.

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1 retracted

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BackgroundMethod
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Nicotinamide mononucleotide adenylyltransferase expression in mitochondrial matrix delays Wallerian degeneration
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BackgroundResultInfluential
Regulation of Dopaminergic Loss by Fas in a 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Model of Parkinson's Disease
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Recent clinical failures in Parkinson's disease with apoptosis inhibitors underline the need for a paradigm shift in drug discovery for neurodegenerative diseases
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JNK2 and JNK3 combined are essential for apoptosis in dopamine neurons of the substantia nigra, but are not required for axon degeneration
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See all 1,012

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
DOI: 10.1002/ana.21995
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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

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Clinical progression in Parkinson disease and the neurobiology of axons

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