Codrugs Linking <scp>l</scp>-Dopa and Sulfur-Containing Antioxidants: New Pharmacological Tools against Parkinson’s Disease

Pinnen, Francesco; Cacciatore, Ivana; Cornacchia, Catia; Sozio, Piera; Cerasa, Laura Serafina; Iannitelli, Antonio; Nasuti, Cinzia; Cantalamessa, Franco; Sekar, Durairaj; Gabbianelli, Rosita; Falcioni, Maria Letizia; Stefano, Antonio Di

doi:10.1021/jm801266x

Cited by 53 publications

(22 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most frequent cofactor for these co-drugs is l-dopa. L-dopa has been conjugated to a number of other agents including entacapone (a COMT inhibitor marketed under the trade name Stalevo®) [240], cysteine [241], N-acetyl cysteine [242], l-Methionine [241], lipoic acid [243], caffeic acid and carnosine [244]. Co-drugs have been made that directly link GSH and L-dopa [245, 246].…”

Section: Gsh and Precursor Delivery As A Therapy For Parkinson’s Diseasementioning

confidence: 99%

Glutathione metabolism and Parkinson's disease

Smeyne

2013

Free Radical Biology and Medicine

357

240

View full text Add to dashboard Cite

It has been established that oxidative stress, defined as the condition when the sum of free radicals in a cell exceeds the antioxidant capacity of the cell, contributes to the pathogenesis of Parkinson’s disease. Glutathione is a ubiquitous thiol tripeptide that acts alone, or in concert with enzymes within cells to reduce superoxide radicals, hydroxyl radicals and peroxynitrites. In this review, we examine the synthesis, metabolism and functional interactions of glutathione, and discuss how this relates to protection of dopaminergic neurons from oxidative damage and its therapeutic potential in Parkinson’s disease.

show abstract

Section: Gsh and Precursor Delivery As A Therapy For Parkinson’s Diseasementioning

confidence: 99%

Glutathione metabolism and Parkinson's disease

Smeyne

2013

Free Radical Biology and Medicine

357

240

View full text Add to dashboard Cite

show abstract

“…12,13 NAC was originally introduced therapeutically for the treatment of obstructive lung diseases 14 and as a drug to treat paracetamol overdose. 15 Recently, several studies have reported that NAC may also be useful in the treatment of a variety of acute and chronic inflammatory conditions, such as human immunodeficiency virus (HIV)-1 infection, 16 and several neurodegenerative diseases, such as Parkinson's disease 17 and light-induced photoreceptor cell damage. 18 Here we report the up-regulation of 4-hydoroxy-2-nonenal (HNE)-modified protein, an oxidative stress marker, and nuclear factor (NF)-κB, a redox-sensitive transcription factor, in experimental CNV.…”

Section: Suppression Of Cnv By N-acetyl-cysteine In Micementioning

confidence: 99%

Suppression of Choroidal Neovascularization by N-Acetyl-Cysteine in Mice

Hara

Inomata

Kawaji

et al. 2010

Current Eye Research

View full text Add to dashboard Cite

show abstract

“…Sulfur-containing amino acids have gained great attention as source of thiols for GSH synthesis [82]. A series of multifunctional thiol codrugs ( 9 – 14 ) were synthesized to overcome the prooxidant effect associated with LD therapy in parkinsonian models (Figure 6) [81].…”

Section: Medicinal-chemistry-based Strategies To Increase Gsh Levelsmentioning

confidence: 99%

Recent Advances in the Treatment of Neurodegenerative Diseases Based on GSH Delivery Systems

Cacciatore

Baldassarre

Fornasari

et al. 2012

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

Neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease(AD), are a group of pathologies characterized by a progressive and specific loss of certain brain cell populations. Oxidative stress, mitochondrial dysfunction, and apoptosis play interrelated roles in these disorders. It is well documented that free radical oxidative damage, particularly on neuronal lipids, proteins, DNA, and RNA, is extensive in PD and AD brains. Moreover, alterations of glutathione (GSH) metabolism in brain have been implicated in oxidative stress and neurodegenerative diseases. As a consequence, the reduced GSH levels observed in these pathologies have stimulated a number of researchers to find new potential approaches for maintaining or restoring GSH levels. Unfortunately, GSH delivery to the central nervous system (CNS) is limited due to a poor stability and low bioavailability. Medicinal-chemistry- and technology-based approaches are commonly used to improve physicochemical, biopharmaceutical, and drug delivery properties of therapeutic agents. This paper will focus primarily on these approaches used in order to replenish intracellular GSH levels, which are reduced in neurodegenerative diseases. Here, we discuss the beneficial properties of these approaches and their potential implications for the future treatment of patients suffering from neurodegenerative diseases, and more specifically from PD and AD.

show abstract

Codrugs Linking l-Dopa and Sulfur-Containing Antioxidants: New Pharmacological Tools against Parkinson’s Disease

Cited by 53 publications

References 34 publications

Glutathione metabolism and Parkinson's disease

Glutathione metabolism and Parkinson's disease

Suppression of Choroidal Neovascularization by N-Acetyl-Cysteine in Mice

Recent Advances in the Treatment of Neurodegenerative Diseases Based on GSH Delivery Systems

Contact Info

Product

Resources

About