1,721,044 research outputs found
Biochemical and therapeutic effects of antioxidants in the treatment of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis
No full textBioethanol production from steam-pretreated corn stover through an isomerase mediated process
No full textAgricultural by-products such as corn stover are considered strategic raw materials for the production of second-generation bioethanol from renewable and non-food sources. This paper describes the conversion of steam-pretreated corn stover to ethanol utilising a multi-step process including enzymatic hydrolysis, isomerisation, and fermentation of mixed hydrolysates with native Saccharomyces cerevisiae. An immobilised isomerase enzyme was used for the xylose isomerisation along with high concentrations of S. cerevisiae. The objective was to assess the extent of simultaneity of the various conversion steps, through a detailed analysis of process time courses, and to test this process scheme for the conversion of lignocellulosic hydrolysates containing several inhibitors of the isomerase enzyme (e.g. metal ions, xylitol and glycerol).The process was tested on two types of hydrolysate after acid-catalysed steam pretreatment: (a) the water soluble fraction (WSF) in which xylose was the largest carbon source and (b) the entire slurry, containing both cellulose and hemicellulose carbohydrates, in which glucose predominated.The results indicated that the ethanol concentration rose when the inoculum concentration was increased in the range 10-75g/L. However, when xylose was the largest carbon source, the metabolic yields were higher than 0.51gethanol/gconsumed sugars probably due to the use of yeast internal cellular resources. This phenomenon was not observed in the fermentation of mixed hydrolysates obtained from the entire pretreated product and in which glucose was the largest carbon source. The ethanol yield from biomass suspensions with dry matter (DM) concentrations of 11-12% (w/v) was 70% based on total sugars (glucose, xylose, galactose). The results suggest that xylulose uptake was more effective in mixed hydrolysates containing glucose levels similar to, or higher than, xylose.Analysis of the factors that limit isomerase activity in lignocellulosic hydrolysates excluded any inhibition due to residual calcium ions after the detoxification of the hemicellulose hydrolysates with Ca(OH)2. By contrast, most of the enzyme activity ceased during the fermentation of the entire slurry after steam explosion, probably due to synergistic inhibition effects of various fermentation co-products. © 2014 Elsevier B.V
Serotonin control of central dopaminergic function: focus on in vivo microdialysis studies
No full textIn this review, the functional interactions between serotonin (5-HT) and dopamine (DA) neuronal systems are discussed with the focus on microdialysis studies in the rodent brain (mainly rats). 5-HT by itself is involved both directly and indirectly via actions on complex neuronal circuitry, in the regulation of DA release through multiple 5-HT receptors, playing a critical role in the development of normal and abnormal behaviours. Recent evidence suggests that dysfunction of dopaminergic and serotoninergic neurotransmitter systems contributes to various disorders including depression, schizophrenia, Parkinson's disease and drug abuse. Here we summarize recent neurochemical works that have extensively explored the role of 5-HT receptors in the control of DA central systems in both basal and drug-induced conditions, using in vivo microdialytic techniques. Several 5-HT receptor subtypes, including the 5-HT(1A), 5-HT(1B), 5-HT(2A), 5-HT(3) and 5-HT(4) receptors, act to facilitate DA release, while the 5-HT(2C) receptor mediates an inhibitory effect of 5-HT on DA release. Taken together, neurochemical approaches using microdialysis can not only contribute to clarification of the physiological role of the serotonergic neuronal systems but may also be a powerful pharmacological approach for the development of therapeutic strategies to the treatment of depression, schizophrenia, Parkinson's disease and drug abuse
Neurodegenerative disorders: from molecules to man (part 1)
No full textNeurons are typically post-mitotic cells. This means that they are expected to have a life span comparable to that of their
carriers. Unfortunately, sometimes, they die prematurely as a result of complex processes known as “neurodegeneration”.
Neurodegenerative diseases are now generally considered a group of disorders that seriously and progressively impair the
functions of the nervous system through causing the selective neuronal vulnerability of specific brain regions.
Neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer Disease (AD), Multiple Sclerosis (MS), and prion
disease represent several distinct categories of disease and each manifests its own unique symptoms. However, the diseases
share several common features, particularly the aggregation and deposition of abnormal proteins. Neurodegenerative disorders
are associated with high morbidity, and few or no effective treatments have been available until now. Neurodegenerative
diseases represent a threat to mankind in a variety of guises and induce chronic suffering and debilitation in about 2% of the
worldwide population. Moreover, the increase in lifespan of western populations will mean that these neurodegenerative
diseases will become more common. Consequently, it is estimated that the number of PD patients will double to between 8.7
and 9.3 million by 2030. As a group, these disorders are a major burden on health care systems compared with other causes of
death and the costs of treatment are expected to rise sharply. Despite the enormous amount of progress we have made in terms
of understanding the aetiologies of these diseases in the last few years, important questions remain unanswered. This special
number deals with this hot topic and is produced by leading groups in the neuroscience field with the aim of summarizing
recent advances in genetic, epideniological, molecular and cellular biology research that have increased our knowledge of the
mechanisms that give rise to degenerative processes and, in general, to alterations of the structure and function of the nervous
system. These contributions give insight into new pharmacological therapies for their treatment and review new and old drugs
aimed at interrupting or at attenuating different pathogenic pathways of neurodegeneration and/or at ameliorating symptoms.
The pharmaceutical industry faces arguably its most difficult challenge in attempting to develop therapeutics for
neurodegenerative disease. The development of disease-modifying therapeutics that addresses the principal causes of
neurodegenerative disease is still in its infancy.
de Lago and Fernández-Ruiz provide an extensive description of the neuroprotective properties of cannabinoids. They focus
their review on the cellular and molecular mechanisms through which cannabinoids might arrest/delay the degeneration of
specific neuronal subpopulations in neurodegenerative disorders such as PD, HD, multiple sclerosis (MS) and other motorrelated
disorders. The potential use of cannabinoid agonists as novel therapeutic options is based on their antioxidant, antiinflammatory
and anti-excitotoxic properties that allow them to afford neuroprotection in different disorders. Carnevale et al.
review the current information on the reciprocal interactions between glia and neurons that are essential for many critical
functions in brain health and disease. Microglial cells, the brain resident macrophages, and astrocytes, the most prevalent type
of cell in brain, are actively involved in the control of neuronal activities both in developing and adult organisms. At the same
time, neurons influence glial functions, through direct cell-to cell interactions as well as the release of soluble mediators. The
authors concentrate on signals from neurons that may have an active role in controlling glial activation on two major
neurotransmitters: acetylcholine (Ach) and noradrenaline (NA). The cholinergic and adrenergic anti-inflammatory pathways
represent important physiological neuro-immune mechanisms by which the innate and adaptive immune responses are kept in
control. The authors show evidence indicating that such mechanisms play a pivotal role in the inflammatory and immune
processes within the CNS. ACh and NA appear to contribute with their pleiotropic functions to restrain glial activation and
control inflammation and neurodegeneration. The development of specific agonists and compounds slowing the degradation of
ACh and NA or their re-uptake might have therapeutic potential as anti-inflammatory agents for treating chronic
neurodegenerative diseases.
376 CNS & Neurological Disorders - Drug Targets, 2007, Vol. 6, No. 6 Editorial
A separate review by Pérez-De La Cruz et al. describes the catabolic route for tryptophan decomposition known as the
kynurenine pathway. This is not only involved in different neurological disorders, but also possesses neuroactive metabolites
with different biological properties, such as pro-oxidant and antioxidant regulators. They provide an overview on the relevance
of this route for several disorders, and also add some further and recent information on the different biological properties of the
neuroactive metabolites of this pathway and their significance for the design of potential therapies for those disorders involving
excitotoxic, oxidative and inflammatory components.
Nunomura et al. review the role played by oxidative stress in the development and progression of AD and PD providing
consistent evidence that oxidative insult is a significant early event in the pathological cascade of this disorder. Therefore they
show that that pro-longevity gene products such as forkhead transcription factors and sirtuins are involved in the insulin-like
signaling pathway and oxidative stress resistance against aging. An enhancement of the pro-longevity signaling (e.g. caloric
restriction) may be a promising approach as anti-oxidative strategy against age-associated neurodegenerative diseases.
Unterberger and Voigtländer focused their paper on the pathogenic mechanisms of prion diseases. Prion diseases are rare fatal
neurodegenerative disorders that may either occur sporadically, or be inherited or infectiously acquired in humans. Irrespective
of aetiology, they can be transmitted to other individuals, this fact being responsible for the public attention prion diseases have
received especially since the nineteen nineties, when a new variant of Creutzfeldt-Jakob disease linked to the consumption of
prion contaminated beef occurred for the first time in Great Britain. In this review, they discuss actual and potential drug targets
in the context of the pathogenic mechanisms of prion diseases.
The scenario that results from this special issue is that, despite the enormous research focused on neurodegenerative disorders,
the underlying pathophysiology is not yet understood in sufficient detail. The situation is certainly a consequence of the
complex interplay of genes, environment and their myriad interactions. There is not as yet a clear means of establishing
efficacy in slowly progressing, late-onset disorders. Given the nature of these diseases, future therapeutics will need to be
paired with tests for biomarkers indicating onset of brain pathology that precedes overt clinical symptoms. Therefore, it is of
paramount importance to reveal those who are at high risk of developing these neurological disorders and allow them start an
early program of prevention. This might involve a brain-healthy diet, very similar to a heart-healthy diet, and moderate physical
activity with the aim of avoiding the other risk factors known so far.
Vincenzo Di Matteo and Ennio Esposito Giuseppe Di Giovanni
Istituto di Ricerche Farmacologiche "Mario Negri" Dipartimento di Medicina Sperimentale
Consorzio "Mario Negri" Sud Sezione di Fisiologia Umana, “G. Pagano”
Via Nazionale 8 Università degli Studi di Palermo
66030 Santa Maria Imbaro, Chieti Corso Tuköry 129, 90134, Palermo
Italy Italy
E-mail: [email protected]
Editorial [ Neurodegenerative Disorders: From Molecules to Man (Part 2) Guest Editors: Giuseppe Di Giovanni, Vincenzo Di Matteo and Ennio Esposito ]
No full textNEURODEGENERATIVE DISORDERS: FROM MOLECULES TO MA
Serotonin-dopamine interaction: electrophysiological evidence
No full textIn this review, the most relevant data regarding serotonin (5-hydroxytryptamine, 5-HT)/dopamine (DA) interaction in the brain, as studied by both in vivo and in vitro electrophysiological methods, are reported and discussed. The bulk of neuroanatomical data available clearly indicate that DA-containing neurons in the brain receive a prominent innervation from 5-HT originating in the raphe nuclei of the brainstem. Furthermore, this modulation seems to be reciprocal; DA neurons innervate the raphe nuclei and exert a tonic excitatory effect on them. Compelling electrophysiological data show that 5-HT can exert complex effects on the electrical activity of midbrain DA neurons mediated by the various receptor subtypes. The main control seems to be inhibitory, this effect being more marked in the ventral tegmental area (VTA) as compared to the substantia nigra pars compacta (SNc). In spite of a direct effect of 5-HT by its receptors located on DA cells, 5-HT can modulate their activity indirectly, modifying gamma-amino-n-butyric acid (GABA)-ergic and glutamatergic input to the VTA and SNc. Although 5-HT/DA interaction in the brain has been extensively studied, much work remains to be done to clarify this issue. The recent development of subtype-selective ligands for 5-HT receptors will not only allow a detailed understanding of this interaction but also lead to development of new treatment strategies, appropriate for those neuropsychiatric disorders in which an alteration of the 5-HT/DA balance is supposed
Serotonin and Dopamine Interaction: An Overview
No full textCentral serotonergic and dopaminergic systems play a critical role in the regulation of normal and abnormal behaviours. Moreover, recent evidence suggests that the dysfunction of dopamine (DA) and serotonin (5-hydroxytriptamine, 5-HT) neurotransmission might underlie the pathophysiology of neuropsychiatric disorders, including depression, schizophrenia, attention deficit hyperactivity disorders, drug abuse, Gilles de la Tourette's syndrome and Parkinson's disease
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