Special Issue "Neuroprotective Strategies"
QuicklinksA special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".
Deadline for manuscript submissions: 15 August 2010
Special Issue Editor
Guest Editor
Dr. Katalin Prokai-Tatrai
Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA
Website: http://www.hsc.unt.edu/faculty/biography.cfm?id=538
E-Mail:
Interests: Medicinal chemistry: drug design of central nervous system agents; neuropeptides and peptidomimetics; prodrugs for CNS delivery; oxidative stress; estrogens and other phenolic antioxidants; protein carbonylation
Published Papers
Special Issue Information
Dear Colleagues,
This special issue is aimed at both the basic science and clinical aspects of neuroprotective approaches to acute (e.g., brain or spinal cord trauma, stroke), and chronic neurodegenerative (e.g., Alzheimer's and Parkinson's diseases, age-related macular degeneration) diseases. Potential and existing interventions, either as reviews or original papers, to prevent neuronal cell death in the CNS and in the periphery are welcome to this special issue. The concept of neuroprotection in therapeutic terms may be best described by Shouldon (Science, 1998; 282:1072) as "pharmacological interventions that produce enduring benefits by favorably influencing underlying etiology or pathogenesis and thereby forestalling onset of disease or clinical decline." Our life span has increased and it brought about a significant increase in the incidence of neurodegenerative diseases. While each neurodegenerative disease has its own characteristics and clinical manifestations, some common markers have been recognized. Among others, increased levels of oxidative/nitrosative damage to DNA, RNA, mitochondria, membranes, and proteins, etc. have been detected in connection with situations of neuronal damage. The wide variety of approaches to rescue neurons includes free radical scavenging antioxidants, ion channel modulators, excitatory amino acid antagonists and neurotrophic factors. Stem-cell based approaches may also represent a new opportunity to treat neurodegenerative diseases. I wish to thank all the authors for their contribution to this special issue.
Katalin Prokai-Tatrai, Ph. D.
Guest Editor
Related Special Issues in other Journals
Neuroprotective Strategies in IJMS
Submission
Keywords
aging; Alzheimer's disease; amyotrophic lateral sclerosis; anti-apoptotic drugs; antioxidants; apoptosis; axon damage; bioavailability; blood-brain barrier; caspases; cognition; excitotoxicity; free radicals; GABA agonists; glaucoma; growth factors; hydroxyl radical; hypothermia; hypoxia; inflammation; ion channels; iron chelators; ischemia; ischemic optic neuropathy; lipid peroxidation; MEK/ERK signaling pathway; mitochondria; necrosis; neurogenesis; neurotrophic factors; nitric oxide synthase; nitrosative/oxidative stress; NMDA agonist; nutraceuticals; Parkinson’s disease; peripheral neurons; peroxinitrite; posttranslational modification; protein aggregates; proteomics; redox-active metals; retinal ganglion cells; spinal cord injury; stem cell; steroids; stroke; superoxide dismutase; therapeutic window; traumatic brain injury
Planned Papers
Manuscript ID: molecules-Neupro-20090718-Le-us
Type of Paper: Review
Title: Autophagy and Neuroprotection in Neurodegenerative Diseases
Authors: Yuncheng Wu MD, PhD1,2, Weidong Le MD, PhD*1
Affiliations: 1Department of Neurology, Baylor College of Medicine, Houston TX 77030
2Department of Neurology, Shanghai First People’s Hospital, Shanghai Jiao Tong University, Shanghai 200080, China; E-mail: weidongl@bcm.tmc.edu
Abstract: It has been suggested that protein misfolding and aggregation contribute significantly to the development of the neurodegenerative diseases. Misfolded and aggregated proteins are cleared by ubiquitin proteasomal system (UPS) and autophagy lysosomal pathway (ALP). Autophagosomal dysfunction has been implicated in an increasing number of diseases including neurodegeneration. Autophagy is a cellular self-eating process that plays an important role in neuroprotection as well as neuronal injury and death. While a decrease in autophagic activity appears to interfere with protein degradation and possibly organelle turnover, increased autophagy has been shown to facilitate the clearance of aggregation-prone proteins and promote neuronal survival in a number of disease models. On the other hand, too much autophagic activity can be detrimental, suggesting the regulation of autophagy has an important role dictating cell fate. In this review paper, we will firstly discuss the pathways underlying autophagy and its dual role in neuronal cell death and survival. The secondly, we will evaluate the role of autophagy in neurodegenerative diseases including Parkinson disease, Alzheimer disease, ALS and etc. The thirdly, we will explore the therapeutic promise of autophagy modifiers and the potential side effects of such treatments.
Manuscript ID: Molecules-Neupro-20090721- Fornai-it
Title: The Biochemical Basis of Lithium-Induced Neuroprotection
Type of Paper: Review
Authors: Alessia Scatena, Federica Fulceri.and Francesco Fornai*; *Email: f.fornai@med.unipi.it
Abstract: Lithium salts have been used in the treatment of bipolar disorder for over 50 years. At present, there is a renewed interest in lithium based on its neuroprotective efficacy. In fact, several studies demonstrated neurotrophic/neuroprotective effects of lithium in vitro, in animal models, and even in humans. Because lithium is ubiquitous within the cell and it is known to target different molecules, thus affecting multiple (and often opposite) pathways with final effect which critically depend on the dose, it is possible that the pharmacological action of lithium cannot be explained by a single mechanism of action. Research has mainly focused on inhibition of IMPase and GSK-3beta as main therapeutic targets of lithium. These enzymes play a pivotal role in many neuronal pathways including autophagy modulation, growth factors synthesis and several cytoprotective effects including antiapoptotic properties. In this review we discuss the biochemical basis of lithium action related to neuroprotection in neuronal cell death occurring in neurodegenerative disorders, prion diseases, epilepsy and ischemia. In particular we consider the various biochemical pathways which are altered by lithium ion and the structure-activity properties leading to neuroprotection.
Manuscript ID: Molecules-neropro-20090723-Hardeland-de
Title: Neuroprotection by Radical Avoidance: Search for Suitable Agents Type of Paper: Review
Author: Rüdiger Hardeland
Affiliation: Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, Berliner Str. 28, D-37073 Göttingen, Germany; Email: rhardel@gwdg.de
Abstract: Neurodegeneration is frequently associated with damage by free radicals. However, rises in reactive oxygen and nitrogen species, which may ultimately lead to neuronal cell death, do not necessarily reflect its primary cause, but can be a consequence of otherwise induced cellular dysfunction. Detrimental processes which promote free radical formation are initiated, e.g., by disturbances in calcium homeostasis, mitochondrial malfunction, and an age-related decline in the circadian oscillator system. Free radicals generated at high rates under pathophysiological conditions are insufficiently detoxified by scavengers. Interventions at the primary causes of dysfunction, which avoid secondary rises in radical formation, may be more efficient. The aim of such approaches should be to prevent calcium overload, to reduce mitochondrial electron dissipation, to support electron transport capacity, and to avoid circadian perturbations.
l-Theanine and several amphiphilic nitrones are capable of counteracting excitotoxicity and/or mitochondrial radical formation. Resveratrol seems to promote mitochondrial biogenesis. Mitochondrial effects of leptin include attenuation of electron leakage. Melatonin combines all the requirements mentioned, additionally regulates anti- and pro-oxidant enzymes and is, with few exceptions, very well tolerated. In this review, the perspectives, problems and limits of drugs are compared which may be suitable for reducing the formation of free radicals.
Manuscript ID: Molecules-neropro-20090803-van Bel-nl
Type of the paper: review
Title: Neuroprotective strategies following perinatal hypoxia-chemia: the potential of selective nitric oxide synthase inhibitors
Authors: Cacha Peeters-Scholte 1, Frank van Bel 2
2 Dept of Neonatology, Wilhelmina Children’s Hospital/University Medical Center, Utrecht, The Netherlands; Email: F.vanBel@umcutrecht.nl
Manuscript ID: Molecules-neupro-20090902-Iriti-it
Type of Paper: Review
Affiliations: 1 Dipartimento di Produzione Vegetale, Università di Milano, via Celoria 2, 20133 Milano, Italy; E-mail: marcello.iriti@unimi.it
2 Dipartimento di Biologia, Università di Milano, via Celoria 26, 20133 Milano, Italy
3 Orto Botanico ‘GE Gherardi’, Toscolano Maderno, Università di Milano, 20133 Milano, Italy
Abstract: Plant secondary metabolites include an array of bioactive constituents of medicinal and food plants able to improve human health. The exposure to these phytochemicals, including phenylpropanoids, isoprenoids and alkaloids, through correct dietary habits, may promote health benefits, protecting against the chronic degenerative disorders mainly spread in western industrialized countries, such as cancer, cardiovascular and neurodegenerative diseases. In this review, we briefly deal with some plant foods and herbs of traditional medicines and diets, focusing on their components active in neuroprotection. Because oxidative stress and neuroinflammation resulting from neuroglial activation, at level of neurons, microglial cells and astrocytes, are key factors in the etiopathogenesis of both neurodegenerative and neurological diseases, emphasis will be attributed to the antioxidant and anti-inflammatory activity exerted by specific molecules present in food plants or in remedies prescribed by herbal medicines.
Manuscript ID: Molecules-neupro-200914-Jung-us
Type of Paper: Article
Title: Neurodamage by and Neuroprotection against Unmanaged Alcohol Withdrawal
Authors: Marianna E. Jung and Daniel B. Metzger
Affiliation: Department of Pharmacology and Neuroscience, University of North Texas, Health Science Center at Fort Worth, 3500 Camp Bowie Blvd., Fort Worth, TX 76107-2699, USA; E-Mail: mjung@hsc.unt.edu
Abstract: Unmanaged sudden withdrawal from excessive consumption of alcohol (ethanol) adversely alters neuronal integrity. Although the magnitudes of injuries vary depending upon the severity of ethanol withdrawal (EW), a body of evidence indicates that irreversible neuronal damages occur in vulnerable brain regions such as cerebellum or hippocampus. Currently benzodiazepines are the only available therapeutic drugs. However, their clinical usage is limited due to serous side effects such as respiratory inhibition and dependence liability. Accordingly, we and others have endeavored to discover mechanisms underlying brain injuries associated with EW and protection against the neuronal injuries. We observed that EW provoked loss of cerebellar neuronal cells in rats and death of cultured hippocampal cells in a manner that was protected by estrogen or estrogen analogues. This article will mainly summarize our previous findings about EW-induced neuronal and cellular toxicity and protection against them through estrogen compounds. We hope that information in this article will help the better understandings of brains' response to EW and endogenous/exogenous defensive strategies, and ultimately for the development of potential estrogen-based treatments for male and female alcoholics.
Manuscript ID: Molecules- Neupro-20091002- Linseman-us
Type of Paper: Review
Title: Nutraceutical Antioxidants as Novel Neuroprotective Agents
Authors: Natalie A. Kelsey1 and Daniel A. Linseman1,2,3
Affiliations: 1Department of Biological Sciences and Eleanor Roosevelt Institute, University of Denver, Denver, Colorado, USA; E-Mail: daniel.linseman@du.edu
2Research Service, Veterans Affairs Medical Center, Denver, Colorado, USA
3Division of Clinical Pharmacology and Toxicology, Department of Medicine, University of Colorado Denver, Denver, Colorado, USA
Abstract: A variety of antioxidant compounds derived from natural products (nutraceuticals) have demonstrated neuroprotective activity in either ro or in vivo models of neuronal cell death or neurodegeneration, respectively. These natural antioxidants fall into several distinct groups based on their chemical structures: 1) flavonoid polyphenols like epigallocatechin 3-gallate (EGCG) from green tea and quercetin from apples; 2) non-flavonoid polyphenols such as curcumin from tumeric and resveratrol from grapes; 3) phenolic acids or phenolic diterpenes such as rosmarinic acid or carnosic acid, respectively, both from rosemary; and 4) organosulfur compounds including the isothiocyanate, L-sulforaphane, from broccoli and the thiosulfonate, allicin, from garlic. All of these compounds are generally considered to be antioxidants. They may be classified this way either because they directly scavenge free radicals or they indirectly increase endogenous cellular antioxidant defenses, for example, via activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) transcription factor pathway. Alternative mechanisms of action have also been suggested for the neuroprotective effects of these compounds such as modulation of signal transduction cascades or effects on gene expression. Here, we will review the literature pertaining to these various classes of nutraceutical antioxidants and discuss their potential therapeutic value in neurodegenerative diseases.
Manuscript ID: Molecules-Neupro-20091118-Prokai-us
Type of Paper: Review
Title: Current Trends in Neuroprotection by Estrogen Therapy
Authors: Istvan Merchenthaler 1 and Laszlo Prokai 2
Affiliations: 1 Department of Epidemiology and Anatomy/Neurobiology, University of Maryland at Baltimore, School of Medicine, 10 S. Pine Str. MSTF Room 9-00F, Baltimore, MD 21201, USA; E-Mail: imerchen@epi.umaryland.edu (I.M.)
2 Department of Molecular Biology and Immunology, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA; E-Mail: lprokai@hsc.unt.edu (L.P.)
Abstract: As the human population ages, women spend half of their lives in a post-menopausal, estrogen-deprived state. Demographics projects a devastating increase in the prevalence of neurodegenerative diseases reinforcing thereby the need for developing novel and safe remedies, including estrogen therapy (ERT) and/or hormone (estrogen plus progestin) therapy (HT). Besides their function as female sex hormones, estrogens also exhibit neurotrophic properties and protect neurons from a variety of harmful insults. All the current estrogen products approved for ERT/HT non-selectively bind to and regulate the two isoforms of the estrogen receptor (ER), ERα and ERβ. However, the activation of ERα, the predominant form in the periphery, by estrogens causes the proliferation of cells, which increases the risk of breast and endometrial cancer. Focusing on protection against hypoxia-induced neurodegeneration and implicating other related maladies such as Alzheimer’s disease and menopausal symptoms, this review summarizes recent strategies for the development of safer estrogen therapies that would have beneficial effects in the central nervous system (CNS) without exhibiting significant side effects in the periphery. Initial efforts to develop non-feminizing estrogens moved toward developing neuro-selective estrogen receptor modulators (neuro-SERMs). Agents that selectively activate ERβ are particularly attractive alternative for ERT/HT, because ERβ acts as a tumor suppressor that inhibits the growth of breast cancer cells and does not exhibit any proliferative effects on the mammary glands and uterus of rodents. Several in vitro and in vivo studies suggest that either synthetic ERβ ligands or some soy isoflavone products, particularly S-equol, may fulfill the criteria to become qualified neuro-SERMs. Another strategy to concentrate the effect of estrogens on the CNS is based on the prodrug approach. CNS-targeting estrogen prodrugs are expected to distribute into or retained preferentially by the CNS where they are converted via an enzyme-catalyzed mechanism to the neuroprotective estrogens reducing thereby peripheral exposure to estrogen. Therefore, the use of these prodrugs for ERT/HT would reduce or eliminate uterotrophic and mammotrophic liabilities currently associated with conventional therapies.
Last update: 4 March 2010