Pathology associated with sporadic Parkinson’s disease — where does it end?

Braak, Heiko; Müller, Christian M.; Rüb, Udo; Ackermann, Hilmar; Bratzke, H.; Vos, Rob A. I. de; Tredici, Kelly Del

doi:10.1007/978-3-211-45295-0_15

Cited by 119 publications

(104 citation statements)

References 47 publications

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“…Braak and coworkers have also identified Lewy bodies in numerous non-dopaminergic brain regions including the locus coeruleus, raphe nuclei, thalamus, amygdala, olfactory nuclei, pedunculopontine nucleus, and cerebral cortex [5,6]. These observations are in agreement with much earlier studies, which indicated that multiple CNS neuronal systems are affected in Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication.…”

Section: Parkinson's Disease and The Nicotinic Cholinergic Systemsupporting

confidence: 82%

“…Receptor studies with 3 H-nicotine also demonstrate ~50% decline in striatum, as well as in other areas including substantia nigra, cortex and hippocampus [98][99][100][101]. These latter findings support the contention that there is a generalized loss of neuronal integrity in Parkinson's disease [5,6]. As in the rodent and monkey studies, declines in α6β2* nAChRs in Parkinson's disease brains are significantly greater than in α4β2* receptors in some striatal regions, as evaluated using receptor binding assays [103,104].…”

Section: Humansmentioning

confidence: 52%

“…There is a ≥70% decline in striatal dopamine and ≥50% loss of nigral dopaminergic neurons with the onset of clinical symptoms, which include bradykinesia, rigidity, and tremor [1][2][3][4]. Although Parkinson's disease has primarily been considered a dopaminergic disorder, it is becoming increasingly clear that multiple CNS systems are involved in its pathogenesis [5][6][7]. Braak and coworkers have also identified Lewy bodies in numerous non-dopaminergic brain regions including the locus coeruleus, raphe nuclei, thalamus, amygdala, olfactory nuclei, pedunculopontine nucleus, and cerebral cortex [5,6].…”

Section: Parkinson's Disease and The Nicotinic Cholinergic Systemmentioning

confidence: 99%

“…Although Parkinson's disease has primarily been considered a dopaminergic disorder, it is becoming increasingly clear that multiple CNS systems are involved in its pathogenesis [5][6][7]. Braak and coworkers have also identified Lewy bodies in numerous non-dopaminergic brain regions including the locus coeruleus, raphe nuclei, thalamus, amygdala, olfactory nuclei, pedunculopontine nucleus, and cerebral cortex [5,6]. These observations are in agreement with much earlier studies, which indicated that multiple CNS neuronal systems are affected in Parkinson's disease [8,9].…”

Section: Parkinson's Disease and The Nicotinic Cholinergic Systemmentioning

confidence: 99%

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Nicotinic receptors as CNS targets for Parkinson's disease

Quik

Bordia

O’Leary

2007

Biochemical Pharmacology

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Parkinson's disease is a debilitating neurodegenerative movement disorder characterized by damage to the nigrostriatal dopaminergic system. Current therapies are symptomatic only and may be accompanied by serious side effects. There is therefore a continual search for novel compounds for the treatment of Parkinson's disease symptoms, as well as to reduce or halt disease progression. Nicotine administration has been reported to improve motor deficits that arise with nigrostriatal damage in parkinsonian animals and in Parkinson's disease. In addition, nicotine protects against nigrostriatal damage in experimental models, findings that have led to the suggestion that the reduced incidence of Parkinson's disease in smokers may be due to the nicotine in tobacco. Altogether, these observations suggest that nicotine treatment may be beneficial in Parkinson's disease. Nicotine interacts with multiple nicotinic receptor (nAChR) subtypes in the peripheral and central nervous system, as well as in skeletal muscle. Work to identify the subtypes affected in Parkinson's disease is therefore critical for the development of targeted therapies. Results show that striatal α6β2-containing nAChRs are particularly susceptible to nigrostriatal damage, with a decline in receptor levels that closely parallels losses in striatal dopamine. In contrast, α4β2-containing nAChRs are decreased to a much smaller extent under the same conditions. These observations suggest that development of nAChR agonists or antagonists targeted to α6β2-containing nAChRs may represent a particularly relevant target for Parkinson's disease therapeutics. Keywordsα-ConotoxinMII; Nicotine; Nicotinic; Parkinson's disease; Nigrostriatal; Striatum Parkinson's disease and the nicotinic cholinergic systemThe pathological hallmarks of Parkinson's disease are the presence of intracellular Lewy bodies and an extensive degeneration of the nigrostriatal dopaminergic system. [1][2][3][4]. There is a ≥70% decline in striatal dopamine and ≥50% loss of nigral dopaminergic neurons with the onset of clinical symptoms, which include bradykinesia, rigidity, and tremor [1][2][3][4].Although Parkinson's disease has primarily been considered a dopaminergic disorder, it is becoming increasingly clear that multiple CNS systems are involved in its pathogenesis [5][6][7]. Braak and coworkers have also identified Lewy bodies in numerous non-dopaminergic brain regions including the locus coeruleus, raphe nuclei, thalamus, amygdala, olfactory nuclei, pedunculopontine nucleus, and cerebral cortex [5,6]. These observations are in agreement with much earlier studies, which indicated that multiple CNS neuronal systems are affected in Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the...

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Section: Parkinson's Disease and The Nicotinic Cholinergic Systemsupporting

confidence: 82%

Section: Humansmentioning

confidence: 52%

Section: Parkinson's Disease and The Nicotinic Cholinergic Systemmentioning

confidence: 99%

Section: Parkinson's Disease and The Nicotinic Cholinergic Systemmentioning

confidence: 99%

See 2 more Smart Citations

Nicotinic receptors as CNS targets for Parkinson's disease

Quik

Bordia

O’Leary

2007

Biochemical Pharmacology

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“…97 Accordingly, the damage to SN pars compacta occurs later in the course of the disease, whereas other brain areas and peripheral tissues are initially affected at the pre-symptomatic phase of the disease. Currently, available measures of neuroprotection are indirect and comprise functional imaging and clinical outcomes, however, which do not always correlate.…”

Section: Transcriptomic Signatures For Evaluation Of Clinical Efficacmentioning

confidence: 99%

Biomarkers for Evaluation of Clinical Efficacy of Multipotential Neuroprotective Drugs for Alzheimer's and Parkinson's Diseases

et al. 2009

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Summary: During the last century, the world population has shown a staggering increase in its proportion of elderly members and thus neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD), respectively, are becoming an increasing burden on society. Among the diverse, significant challenges facing clinicians, is the improvement of diagnostic measures to detect early and subtle symptoms, a phase in which prevention efforts might be expected to have their greatest impact and provide a measure of disease progression that can be evaluated during the course of drug treatment. At present, clinical diagnosis of AD and PD is based on a constellation of symptoms and manifestations, although the disease originated several years earlier. Given the multiple etiological nature of AD and PD, it is reasonable to assume that the initial causative pathobiological processes may differ between the affected individuals. Therefore, the availability of biological markers or biomarkers will help not only early disease diagnosis, but also delineate the pathological mechanisms more definitively and reliably than the traditional cognitive and neurological phenotypes. In the current article, we review the literature on biochemical, genetic, and neuroimaging biomarkers and discuss their predictive value as indicative for disease vulnerability to detect individuals at risk for PD and AD, and to determine the clinical efficacy of novel, disease-modifying (neuroprotective) strategies.

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