Selegiline, a therapeutic agent of Parkinson's disease, and its metabolite, desmethylselegiline, were explored for their neuroprotective effects against N-methyl-D-aspartate (NMDA)-induced cell death in rat retina. Morphometric analysis of the retina revealed that an intravitreal injection of NMDA induced a significant decrease in cell density in the ganglion cell layer and in thickness of the inner plexiform layer, but not of other retinal layers such as the outer nuclear layer. Concurrent intravitreal injection of selegiline with NMDA did not show a significant protective effect, whereas co-injection of desmethylselegiline provided protection from NMDA-induced retinal damage. Parenteral administration (both single and consecutive dosing) of selegiline significantly prevented loss of ganglion cell layer cells. Counting of retinal ganglion cells by fluorescent tracer labeling confirmed that selegiline protected retinal ganglion cells from NMDA toxicity. The selegiline treatment did not produce a significant increase, though it tended to such as effect, in a brain-derived neurotrophic factor (BDNF) level in the retina, when compared with the NMDA-treated control group. These results indicate that parenteral treatment with selegiline rescues inner retinal cells from NMDA-induced neural damage, and that desmethylselegiline may contribute, in part, to the protective activities of selegiline. The neuroprotective effects exerted by selegiline may be attributed partially to a change in the retinal BDNF expression.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0014-2999(02)02729-2 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Fluorinated Coumarin Derivatives as Selective PET Tracer for MAO-B Imaging.
J Med Chem
December 2024
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.
Monoamine oxidase-B (MAO-B), predominantly exists on the outer mitochondrial membrane of astrocytes, serves as a crucial biomarker for reactive astrocytes during neuroinflammatory responses and various neurodegenerative diseases. In this study, we synthesized a series of fluorinated coumarin derivatives and evaluated their structure-activity relationship and subtype selectivity for MAO-B. Following this, the preclinical bioevaluation containing positron emission tomography (PET) imaging and autoradiography studies led to the identification of the novel PET tracer, [F], which demonstrated high affinity for MAO-B (IC = 0.
View Article and Find Full Text PDFFeasibility of Simon 2-Stage Futility Trials in Early Parkinson Disease: Analysis of the PRECEPT and DATATOP Trial Datasets.
Neurology
January 2025
From the Department of Clinical Neurosciences (M.W.K., J.R.S.), University of Calgary, Alberta; Division of Neurology (L.V.K.), Department of Medicine, Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario; Department of Medicine (D.W.), University of British Columbia Southern Medical Program, Kelowna; Division of Neurology (T.A.M., M.G.S.), Department of Medicine, University of Ottawa, The Ottawa Hospital Ottawa, Ontario, Canada; Department of Neurology (J.M.), Rijnstate Hospital, Arnhem; Department of Neurology (E.M.M.S., B.U.), MS Center Amsterdam, Amsterdam University Medical Centers, the Netherlands; Section on Statistical Planning and Analysis (A.S.), Department of Neurology, UT Southwestern Medical Center, Dallas; and Department of Biostatistics (G.R.C.), University of Alabama at Birmingham.
Background And Objectives: Disease-modifying treatments (DMTs) are a major unmet need in Parkinson disease (PD). To date, trials investigating DMT candidates in PD most often used a randomized controlled trial (RCT) design. Unfortunately, RCTs to date have not led to a breakthrough, in part because of the large sample sizes and length of follow-up required.
View Article and Find Full Text PDFProminent Neuroprotective Potential of Indole-2--methylpropargylamine: High Affinity and Irreversible Inhibition Efficiency towards Monoamine Oxidase B Revealed by Computational Scaffold Analysis.
Pharmaceuticals (Basel)
September 2024
Laboratory for the Computational Design and Synthesis of Functional Materials, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, 10000 Zagreb, Croatia.
: Monoamine oxidases (MAO) are flavoenzymes that metabolize a range of brain neurotransmitters, whose dysregulation is closely associated with the development of various neurological disorders. This is why MAOs have been the central target in pharmacological interventions for neurodegeneration for more than 60 years. Still, existing drugs only address symptoms and not the cause of the disease, which underlines the need to develop more efficient inhibitors without adverse effects.
View Article and Find Full Text PDFDesign, Synthesis, Molecular Docking, Pharmacokinetic Properties, and Molecular Dynamics Simulation of Sulfonyl Derivatives of Benzimidazole against Parkinson's Disease.
Curr Med Chem
October 2024
Department of Chemistry, Cooch Behar Panchanan Barma University, Cooch Behar, West Bengal, 736101, India.
Article Synopsis
- Parkinson's disease (PD) is a rapidly increasing global health issue with no cure, prompting the need for new drug development.
- The study focused on synthesizing and testing sulfonyl derivatives of benzimidazole as potential treatments by targeting monoamine oxidase B (MAO-B) using molecular docking techniques.
- Results showed that two synthesized compounds exhibited strong binding affinities, suggesting they could be promising candidates for effective PD therapies compared to existing drugs.
Unveiling the Therapeutic Potential of Small Molecule of SVAK-12: A Comprehensive In Silico, In Vitro, and In Vivo Studies on its Neuroprotective Effects and Molecular Interactions in Parkinson's Disease.
Curr Med Chem
October 2024
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
Article Synopsis
- Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopamine-producing cells, and current treatments are not definitive.
- The study explored the potential of SVAK-12, a small molecule capable of crossing the blood-brain barrier, to improve cell viability and reduce neurotoxicity in various experimental settings, including in vitro, in vivo, and through molecular simulations.
- Results showed that SVAK-12 increased levels of key neurotrophic factors and boosted dopamine expression, making it a promising candidate for treating neurological disorders despite limited impact on motor symptoms in live models.
Want 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!