AI Article Synopsis
- The distinct nAChR subtypes found in specific regions of the CNS offer promising avenues for targeted therapies for neurodegenerative diseases like Parkinson's disease.
- Alpha6-containing nAChRs are particularly localized in the nigrostriatal pathway and uniquely interact with alpha-conotoxinMII, making them significant for understanding their function and potential therapeutic use.
- Studies suggest that alpha6(*) nAChRs play a role in dopamine release and motor behavior, indicating their potential as therapeutic targets for conditions related to the nigrostriatal system.
Article Abstract
The presence of distinct nicotinic acetylcholine receptor (nAChR) subtypes in specific central nervous system (CNS) areas offers the possibility of developing targeted therapies for diseases involving the affected brain region. Parkinson's disease is a neurodegenerative movement disorder characterized by a progressive degeneration of the nigrostriatal system. alpha6-containing nAChRs (designated alpha6(*)1 nAChRs) have a relatively selective localization to the nigrostriatal pathway and a limited number of other CNS regions. In addition to a unique distribution, this subtype has a distinct pharmacology and specifically interacts with alpha-conotoxinMII, a toxin key in its identification and characterization. alpha6(*) nAChRs are also regulated in a novel manner, with a decrease in their number after nicotine treatment rather than the increase observed for alpha4(*) nAChRs. Striatal alpha6(*) receptors were functional and mediate dopamine release, suggesting that they have a presynaptic localization. This is further supported by lesion studies showing that both alpha6(*) nAChR sites and their functions are dramatically decreased with dopaminergic nerve terminal loss, in contrast to only small declines in alpha4(*) and no change in alpha7(*) receptors. Although the role of nigrostriatal alpha6(*) nAChRs is only beginning to be understood, an involvement in motor behavior is emerging. This latter observation coupled with the finding that nicotine protects against nigrostriatal damage suggest that alpha6(*) nAChRs may represent unique targets for neurodegenerative disorders linked to the nigrostriatal system such as Parkinson's disease.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1124/jpet.105.094375 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione protects against MPP-induced neurotoxicity by ameliorating oxidative stress, apoptosis and autophagy in SH-SY5Y cells.
Metab Brain Dis
January 2025
Key Laboratory of Longevity and Aging-Related Disease of Chinese Ministry of Education, Center for Translational Medicine, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, China.
2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) is a cyclohexanedione compound extracted from the roots of Averrhoa carambola L. Several studies have documented its beneficial effects on diabetes, Alzheimer's disease, and cancer. However, its potential neuroprotective effects on Parkinson's disease (PD) have not yet been explored.
View Article and Find Full Text PDFNanotechnology in Parkinson's Disease: overcoming drug delivery challenges and enhancing therapeutic outcomes.
Drug Deliv Transl Res
January 2025
Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India.
The global prevalence of Parkinson's Disease (PD) is on the rise, driven by an ageing population and ongoing environmental conditions. To gain a better understanding of PD pathogenesis, it is essential to consider its relationship with the ageing process, as ageing stands out as the most significant risk factor for this neurodegenerative condition. PD risk factors encompass genetic predisposition, exposure to environmental toxins, and lifestyle influences, collectively increasing the chance of PD development.
View Article and Find Full Text PDFGinkgolide B regulates apoptosis, oxidative stress, and mitochondrial dysfunction in MPP-induced SK-N-SH cells by targeting HDAC4/JNK pathway.
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Huai'an Hospital Affiliated to Yangzhou University, The Fifth People's Hospital of Huai'an), 1 Huaihe East Road, Huaiyin District, Huai'an City, Jiangsu Province, China.
Ginkgolide B (GB) is a bioactive constituent found in Ginkgo biloba leaves that has been long recognized as a protective agent against many neurological disorders. Our study aimed to examine the effect of GB in an in vitro Parkinson's disease (PD) model and to investigate its neuroprotective mechanism as a primary objective. SK-N-SH cells were challenged with 1-methyl-4-phenylpyridinium (MPP) to act as a PD-like model of neuronal damage.
View Article and Find Full Text PDFDynamic Video Assessment of Axial Postural Abnormalities in Parkinson's Disease: A Pilot Study.
Mov Disord Clin Pract
January 2025
Department of Computer Science, University of Verona, Verona, Italy.
Background: Axial postural abnormalities (APAs) are frequent and disabling axial symptoms of Parkinson's disease (PD). Image-based measurement is considered the gold standard but may not accurately detect the true severity of APAs because these symptoms can appear or get worse under dynamic conditions.
Objective: The aim was to evaluate quantitative changes in APAs degree during prolonged standing and walking in both single- and dual-task conditions (motor + cognitive).
The novel p.A30G SNCA pathogenic variant in Greek patients with familial and sporadic Parkinson's disease.
Eur J Neurol
February 2025
1st Department of Neurology, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Background: The p.A53T variant in the SNCA gene was considered, until recently, to be the only SNCA variant causing familial Parkinson's disease (PD) in the Greek population. We identified a novel heterozygous p.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!