Nicotine neuroprotection against nigrostriatal damage: importance of the animal model

Quik, Maryka; O’Neill, Michael; Perez, Xiomara A.

doi:10.1016/j.tips.2007.03.001

Cited by 88 publications

(78 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This finding, together with the usual young disease onset of dyskinetic patients2, might support the notion of a neuroprotective effect of the cholinergic system on nigrostriatal dopamine‐containing neurons 49, 50, 51. In this study, we were not able to properly address a putative neuroprotective effect of the cholinergic system on nigrostriatal dopamine‐containing neurons and disease progression.…”

Section: Discussionmentioning

confidence: 60%

Cholinergic activity and levodopa‐induced dyskinesia: a multitracer molecular imaging study

Brumberg

Küsters

Al‐Momani

et al. 2017

Ann Clin Transl Neurol

View full text Add to dashboard Cite

ObjectiveTo investigate the association between levodopa‐induced dyskinesias and striatal cholinergic activity in patients with Parkinson's disease.MethodsThis study included 13 Parkinson's disease patients with peak‐of‐dose levodopa‐induced dyskinesias, 12 nondyskinetic patients, and 12 healthy controls. Participants underwent 5‐[123I]iodo‐3‐[2(S)‐2‐azetidinylmethoxy]pyridine single‐photon emission computed tomography, a marker of nicotinic acetylcholine receptors, [123I]N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane single‐photon emission computed tomography, to measure dopamine reuptake transporter density and 2‐[18F]fluoro‐2‐deoxyglucose positron emission tomography to assess regional cerebral metabolic activity. Striatal binding potentials, uptake values at basal ganglia structures, and correlations with clinical variables were analyzed.ResultsDensity of nicotinic acetylcholine receptors in the caudate nucleus of dyskinetic subjects was similar to that of healthy controls and significantly higher to that of nondyskinetic patients, in particular, contralaterally to the clinically most affected side.InterpretationOur findings support the hypothesis that the expression of dyskinesia may be related to cholinergic neuronal excitability in a dopaminergic‐depleted striatum. Cholinergic signaling would play a role in maintaining striatal dopaminergic responsiveness, possibly defining disease phenotype and progression.

show abstract

Section: Discussionmentioning

confidence: 60%

Cholinergic activity and levodopa‐induced dyskinesia: a multitracer molecular imaging study

Brumberg

Küsters

Al‐Momani

et al. 2017

Ann Clin Transl Neurol

View full text Add to dashboard Cite

show abstract

“…Construction of the Concatamer ␣4-24-␤2 and ␤2-24-␣4-mECDs-First, the expression plasmid pPICZaA was modified for the construction of the concatamers by inserting the (AGS) 8 -or (AGS) 11 -coding DNA sequence (hybridized oligonucleotides: linker-KpnI-for/linker-SacII-rev and linker33-KpnI-for/linker33-SacII-rev) at the KpnI and SacII sites. The cDNAs for the ␣4-and ␤2-mECDs were then modified by PCR to generate EcoRI/KpnI or SacII/XbaI restriction sites, leading to the generation of four different cDNAs: ␣4-m-EcoRI/KpnI, ␤2-m-SacII/XbaI, ␤2-m-EcoRI/KpnI, and ␣4-m-SacII/XbaI.…”

Section: Methodsmentioning

confidence: 99%

“…␣4␤2 nAChRs are implicated in many pathological conditions, including Alzheimer disease (9,10), Parkinson disease (11), schizophrenia (12), and nicotine addiction (13). As expected, this AChR subtype presents an invaluable target for the development of new drugs acting mainly as nicotinic agonists (14).…”

mentioning

confidence: 99%

Expression of Water-soluble, Ligand-binding Concatameric Extracellular Domains of the Human Neuronal Nicotinic Receptor α4 and β2 Subunits in the Yeast Pichia pastoris

Stergiou

Zisimopoulou

Tzartos

2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels that are responsible for cell communication via the neurotransmitter acetylcholine. The predominant nAChR subtype in the mammalian brain with a high affinity for nicotine is composed of ␣4 and ␤2 subunits. This nAChR subtype is responsible for addiction to nicotine and is thought to be implicated in Alzheimer and Parkinson diseases and therefore presents an important target for drug design. In an effort to obtain water-soluble, ligand-binding domains of the human ␣4␤2 nAChR for structural studies, we expressed the extracellular domains (ECDs) of these subunits in the eukaryotic expression system Pichia pastoris.

show abstract

“…There is also a large body of literature demonstrating nicotine-mediated protection against dopaminergic damage in parkinsonian animal models [22]. In rats, nicotine pre-treatment protects against nigrostriatal degeneration induced by the dopaminergic neurotoxin 6-hydroxydopamine or by mechanical lesions [23][24][25][26][27][28].…”

Section: Nicotine-mediated Protection Against Toxic Insults In Experimentioning

confidence: 99%

Nicotinic receptors as CNS targets for Parkinson's disease

Quik

Bordia

O’Leary

2007

Biochemical Pharmacology

Self Cite

View full text Add to dashboard Cite

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...

show abstract

Nicotine neuroprotection against nigrostriatal damage: importance of the animal model

Cited by 88 publications

References 42 publications

Cholinergic activity and levodopa‐induced dyskinesia: a multitracer molecular imaging study

Cholinergic activity and levodopa‐induced dyskinesia: a multitracer molecular imaging study

Expression of Water-soluble, Ligand-binding Concatameric Extracellular Domains of the Human Neuronal Nicotinic Receptor α4 and β2 Subunits in the Yeast Pichia pastoris

Nicotinic receptors as CNS targets for Parkinson's disease

Contact Info

Product

Resources

About