Etiopathogenesis of Parkinson disease: a new beginning?
- PMID: 19008336
- DOI: 10.1177/1073858408319974
Etiopathogenesis of Parkinson disease: a new beginning?
Abstract
Parkinson disease (PD) probably represents a syndrome of different disorders and origins converging into a relatively uniform neurodegenerative process. Although clinical-pathological studies have suggested that the presymptomatic phase of PD may be relatively short, perhaps less than a decade, the authors postulate that the pathogenic mechanisms may begin much earlier, possibly even in the prenatal period. Thus, some patients with PD may be born with a fewer than normal number of dopaminergic (and nondopaminergic) neurons as a result of genetic or other abnormalities sustained during the prenatal or perinatal period; as a result of normal age-related neuronal attrition, they eventually reach the critical threshold (60% or more) of neuronal loss needed for onset of PD to become clinically manifest. The authors review the emerging evidence that genetic disruption of normal development, coupled with subsequent environmental factors (the so called multiple-hit hypothesis), plays an important role in the etiopathogenesis of PD.
Similar articles
-
Can we image premotor Parkinson disease?Neurology. 2009 Feb 17;72(7 Suppl):S21-6. doi: 10.1212/WNL.0b013e318198df97. Neurology. 2009. PMID: 19221310 Review.
-
Molecular pathogenesis of Parkinson disease.Arch Neurol. 2005 Mar;62(3):353-7. doi: 10.1001/archneur.62.3.353. Arch Neurol. 2005. PMID: 15767499 Review.
-
The progression of Parkinson disease: a hypothesis.Neurology. 2007 Mar 20;68(12):948-52. doi: 10.1212/01.wnl.0000257110.91041.5d. Neurology. 2007. PMID: 17372132
-
Functional imaging in Parkinson disease.Neurology. 2008 Apr 15;70(16 Pt 2):1478-88. doi: 10.1212/01.wnl.0000310432.92489.90. Neurology. 2008. PMID: 18413571 Review.
-
Mechanisms compensating for dopamine loss in early Parkinson disease.Neurology. 2009 Feb 17;72(7 Suppl):S32-8. doi: 10.1212/WNL.0b013e318198e0e9. Neurology. 2009. PMID: 19221312 Review.
Cited by
-
Gestational restraint stress and the developing dopaminergic system: an overview.Neurotox Res. 2012 Jul;22(1):16-32. doi: 10.1007/s12640-011-9305-4. Epub 2012 Jan 4. Neurotox Res. 2012. PMID: 22215534 Review.
-
Animal models of Parkinson's disease: a gateway to therapeutics?Neurotherapeutics. 2014 Jan;11(1):92-110. doi: 10.1007/s13311-013-0234-1. Neurotherapeutics. 2014. PMID: 24158912 Free PMC article. Review.
-
Astrocytes Surviving Severe Stress Can Still Protect Neighboring Neurons from Proteotoxic Injury.Mol Neurobiol. 2016 Sep;53(7):4939-60. doi: 10.1007/s12035-015-9427-4. Epub 2015 Sep 15. Mol Neurobiol. 2016. PMID: 26374549 Free PMC article.
-
Age-related changes in dopamine signaling in Nurr1 deficient mice as a model of Parkinson's disease.Neurobiol Aging. 2012 May;33(5):1001.e7-16. doi: 10.1016/j.neurobiolaging.2011.03.022. Epub 2011 Apr 30. Neurobiol Aging. 2012. PMID: 21531044 Free PMC article.
-
Exposure to an environmental neurotoxicant hastens the onset of amyotrophic lateral sclerosis-like phenotype in human Cu2+/Zn2+ superoxide dismutase 1 G93A mice: glutamate-mediated excitotoxicity.J Pharmacol Exp Ther. 2011 Aug;338(2):518-27. doi: 10.1124/jpet.110.174466. Epub 2011 May 17. J Pharmacol Exp Ther. 2011. PMID: 21586603 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical