Abstract:
:No therapy exists to slow down or prevent Parkinson's disease (PD), a debilitating neurodegenerative disorder. Neurotrophic factors (NTFs) emerged as promising disease-modifying agents in PD and are currently under clinical development. We argue that efforts in three research areas must converge to harness the full therapeutic power of NTFs. First, the physiological roles of NTFs in aging dopaminergic neurons must be comprehensively understood. Second, the mechanisms underlying the neuroprotective, neurorestorative and stimulatory effects of NTFs on diseased neurons need to be defined. Third, improved brain delivery of NTFs and new ways to stimulate NTF signaling are required to achieve clinical benefits. In this review, we discuss progress in these areas and highlight emerging concepts in NTF biology and therapy.
journal_name
Trends Neuroscijournal_title
Trends in neurosciencesauthors
Aron L,Klein Rdoi
10.1016/j.tins.2010.11.001subject
Has Abstractpub_date
2011-02-01 00:00:00pages
88-100issue
2eissn
0166-2236issn
1878-108Xpii
S0166-2236(10)00166-9journal_volume
34pub_type
杂志文章,评审abstract::High levels of expression of Ca2+/phospholipid-dependent protein kinase C (PKC) occur in neuronal tissues and play a strategic role in the modulation of short- and long-term functions (ion channels, receptor desensitization, neurotransmitter release and synaptic efficiency) that become modified during the brain ageing...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(97)01084-9
更新日期:1997-09-01 00:00:00
abstract::It is generally thought that monoamines play a nonspecific role in modulating cortical activity. However, several lines of evidence now indicate that cortical monoaminergic afferents show remarkable anatomical specificity. In particular, there is unequivocal evidence for regional, laminar and intracortical specificity...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/0166-2236(89)90037-4
更新日期:1989-09-01 00:00:00
abstract::The ability to map functional activity in the living human brain has rekindled interest in the organization of human neural circuitry specifically and in animal neural circuitry generally. Faced with incredible complexity, researchers are turning to the power of computer graphics for two- and three-dimensional interac...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/0166-2236(95)92766-j
更新日期:1995-11-01 00:00:00
abstract::Imagine the decisions you might make while playing a simple game like 'matching pennies'. At each play, you and your opponent, say the mathematician John vonNeumann, each lay down a penny heads or tails up. If both pennies show the same side, vonNeumann wins, if not, you win. Before each play, you have the subjective ...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(00)01932-9
更新日期:2001-11-01 00:00:00
abstract::Synaptically released glutamate activates extrasynaptic receptors; such actions are controlled by glutamate uptake. Recent experimental findings show that there are many more glutamate transporters on the postsynaptic than presynaptic side of the vicinity of central synapses. This asymmetry favours activation of axona...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(02)02230-0
更新日期:2002-10-01 00:00:00
abstract::The two GluN3 subunits were the last NMDA receptor subunits to be cloned some 15 years ago. Strikingly, despite the steadily growing interest in their function, their physiological role remains elusive. The original billing as dominant-negative modulators of classical NMDA receptors composed of GluN1 and GluN2 subunit...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2011.11.010
更新日期:2012-04-01 00:00:00
abstract::Serotonin (5-HT) 5-HT(3) receptors are ligand-gated ion channels, which are generally thought to be involved in the presynaptic modulation of neurotransmitter release. However, analysis of published data reveals that most of the evidence for the alleged presynaptic role of 5-HT(3) receptors in modulating CNS neurotran...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(00)01662-3
更新日期:2000-12-01 00:00:00
abstract::Inflammation in the central nervous system (CNS) has been linked to demyelination and remyelination. Using zebrafish and mouse models of demyelination and remyelination, Cunha et al. now describe a novel role for myeloid differentiation factor 88 (MyD88) signaling in supporting remyelination by promoting myeloid cell-...
journal_title:Trends in neurosciences
pub_type: 评论,杂志文章
doi:10.1016/j.tins.2020.04.005
更新日期:2020-07-01 00:00:00
abstract::In the central nervous system (CNS) the function of retinoic acid, the active metabolite of vitamin A, is best understood from its action in guiding embryonic development; as development comes to completion, retinoic acid signaling declines. However, it is increasingly recognized that this signaling mechanism does not...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2012.08.005
更新日期:2012-12-01 00:00:00
abstract::P2X receptors are cation-selective ion channels that open on binding to extracellular ATP; they play a role in fast synaptic transmission between neurones, and from autonomic nerves to smooth muscles. Isolation of cDNAs that encode P2X receptors in the smooth muscle of vas deferens and in phaeochromocytoma cells indic...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/0166-2236(95)93907-f
更新日期:1995-05-01 00:00:00
abstract::Recent opinion surveys suggest that the majority of the public is willing to accept the use of animals in research if high standards of welfare and effective regulation are in place. The public appears unaware that such standards have existed for some time. The scientific community should now re-focus its communicatio...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(00)02035-x
更新日期:2002-03-01 00:00:00
abstract::The human brain can be stimulated by a single intense magnetic pulse over the scalp. Currents induced within the cranium excite the motor cortex and cause limb muscles to contract. The discharge of single motor units, the firing of which is maintained by voluntary effort, can be modulated by magnetic stimuli. Peri-sti...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/0166-2236(91)90029-t
更新日期:1991-09-01 00:00:00
abstract::A general assay for evaluating functional interactions between ligands and G-protein-coupled receptors within minutes has been developed. The system uses the principles employed by animals such as reptiles, amphibians and fish to control their colors. In nature, activation of G-protein-coupled receptors expressed by s...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/0166-2236(94)90087-6
更新日期:1994-04-01 00:00:00
abstract::Compromise of the ubiquitin-proteasome system (UPS) is a potential basis for multiple physiological abnormalities and pathologies in the CNS. This could be because reduced protein turnover leads to bulk intracellular protein accumulation. However, conditions associated with compromised UPS function are also associated...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2006.11.003
更新日期:2007-01-01 00:00:00
abstract::There are pluripotent stem cells in the adult brain that might not be very different from those found in bone marrow. Recent and profound advances in the field of neuropoiesis, which often rely on insights from studies of hematopoiesis and in some instances use cross-paradigms with this field, have already revealed th...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(99)01416-2
更新日期:1999-08-01 00:00:00
abstract::Schizophrenia (SZ) is primarily an adult psychiatric disorder in which disturbances caused by susceptibility genes and environmental insults during early neurodevelopment initiate neurophysiological changes over a long time course, culminating in the onset of full-blown disease nearly two decades later. Aberrant postn...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2009.05.007
更新日期:2009-09-01 00:00:00
abstract::Among the many calcium-binding proteins in the nervous system, parvalbumin, calbindin-D28K and calretinin are particularly striking in their abundance and in the specificity of their distribution. They can be found in different subsets of neurons in many brain regions. Although it is not yet known whether they play a ...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/0166-2236(92)90081-i
更新日期:1992-08-01 00:00:00
abstract::Classical receptive-field concepts have been used to explain local perceptual effects such as border contrast and Mach bands, but are not sufficient to explain global perceptual effects. Examples are the perception of illusory contours, area contrast, color constancy, depth planes, coherent motion and texture contrast...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/0166-2236(96)10038-2
更新日期:1996-10-01 00:00:00
abstract::Neuro-immune interactions are not only vital for the control of neurotropic pathogens, but also appear to influence brain development and homeostasis. During immune surveillance, T cells can patrol the CNS-associated border regions to sense pathogenic alterations. While access to the CNS parenchyma is restricted in th...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2019.07.008
更新日期:2019-10-01 00:00:00
abstract::Currently available antibodies to the P2X(7) receptor are unreliable determinants of neuronal P2X(7) immunoreactivity, owing to staining of a "P2X(7)-like" protein that is not eliminated by legitimate P2X(7) gene-knockout approaches. Despite this, compelling electrophysiological and pharmacological data strongly suppo...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2006.03.003
更新日期:2006-05-01 00:00:00
abstract::It is now clear that cytokines traditionally viewed as immune modulators participate in inflammatory responses within the adult nervous system. However, in the developing nervous system hematolymphopoietic cytokines also play a role unrelated to neural-immune interactions. Instead, many of these factors subserve prima...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(96)01045-4
更新日期:1997-08-01 00:00:00
abstract::The current dominant model of binaural sound localization proposes that the lateral position of a sound source is determined by the position of maximal activation within an array of binaural coincidence-detector neurons that are tuned to different interaural time differences (ITDs). The tuning of a neuron for an ITD i...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/S0166-2236(03)00140-1
更新日期:2003-07-01 00:00:00
abstract::The vertebrate neuromuscular junction (NMJ), a peripheral synapse formed between motoneuron and skeletal muscle, is characterized by a protracted postnatal period of maturation and life-long maintenance. In neuromuscular disorders such as congenital myasthenic syndromes (CMSs), disruptions of NMJ maturation and/or mai...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2012.04.005
更新日期:2012-07-01 00:00:00
abstract::Neurological diseases, including global ischemia, Alzheimer's disease and amyotrophic lateral sclerosis, are characterized by selective patterns of neurodegeneration. Most studies of potential glutamate-receptor-mediated contributions to disease have focused on the highly Ca2+-permeable and widely distributed NMDA-rec...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(00)01610-6
更新日期:2000-08-01 00:00:00
abstract::Axon interruption elicits a complex neuronal response that leaves neurons poised precariously between death and regeneration. The signals underlying this dichotomy are not fully understood. The transcription factor c-Jun is one of the earliest and most consistent markers for neurons that respond to nerve-fiber transec...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(96)01000-4
更新日期:1997-05-01 00:00:00
abstract::Genetic studies have identified several of the genes associated with malformations of cortical development which might disrupt each of the main stages of cell proliferation and specification, neuronal migration and late cortical organization. The largest malformation groups, focal cortical dysplasia, heterotopia and p...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2007.12.004
更新日期:2008-03-01 00:00:00
abstract::Rhythmical brain activity around 5Hz can be observed in the prefrontal cortex under conditions requiring high levels of cognitive control. However, its temporal dynamics are still elusive. A recent research paper (Cooper et al. Neuroimage 2019;189:130-140) provides evidence that the temporal evolution of this frontal-...
journal_title:Trends in neurosciences
pub_type: 评论,杂志文章
doi:10.1016/j.tins.2019.02.006
更新日期:2019-05-01 00:00:00
abstract::Aging is the most important risk factor for common neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Aging in the central nervous system has been associated with elevated mutation load in mitochondrial DNA, defects in mitochondrial respiration and increased oxidative damage. These observations ...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2008.02.008
更新日期:2008-05-01 00:00:00
abstract::Exocytosis in neurones and neuroendocrine cells is triggered by an increase in the cytosolic concentration of Ca2+, and is followed by endocytotic membrane retrieval. Electrophysiological studies have characterized the nature of the Ca2+ signal that is required for exocytosis, and have defined the Ca(2+)-dependent ste...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/0166-2236(95)93900-i
更新日期:1995-04-01 00:00:00
abstract::In the mammalian central nervous system (CNS), coupling of neurons by gap junctions (i.e., electrical synapses) and the expression of the neuronal gap junction protein, connexin 36 (Cx36), transiently increase during early postnatal development. The levels of both subsequently decline and remain low in the adult, conf...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2012.11.001
更新日期:2013-04-01 00:00:00