Abstract：
:Multiple sclerosis (MS), an incurable but manageable disorder, is characterized by chronic inflammatory demyelination and neurodegeneration in the central nervous system. Although the primary cause of this often devastating disease remains elusive, major therapeutic advances have occurred during the past two decades. Here, we present a review of current immunomodulatory treatments and outline upcoming therapy approaches, including biologics and oral alternatives that might have equivalent or superior efficacy and/or enhanced tolerability compared with available treatments, and discuss the scientific rationale and expected benefits and risks for these compounds. We also speculate about alternatives beyond immune-directed approaches, review novel insights into the neurobiological consequences of sustained brain inflammation and evaluate future perspectives for neuroprotective and neuroregenerative treatment strategies for MS.
journal_name
Trends Neuroscijournal_title
Trends in neurosciencesauthors
Aktas O,Kieseier B,Hartung HPdoi
10.1016/j.tins.2009.12.002subject
Has Abstractpub_date
2010-03-01 00:00:00pages
140-52issue
3eissn
0166-2236issn
1878-108Xpii
S0166-2236(09)00201-Xjournal_volume
33pub_type
杂志文章,评审abstract：:The appearance of Santiago Ramón y Cajal in the world of neuroscience provoked a radical change in the course of its history. Cajal's studies of the microanatomy of virtually the whole CNS and his observations regarding degeneration and regeneration, together with his theories about the function, development and plast...
journal_title：Trends in neurosciences
pub_type： 传,历史文章,杂志文章
doi：10.1016/s0166-2236(02)02214-2
更新日期：2002-09-01 00:00:00
abstract：:Since early anatomical descriptions, the existence of dendritic spines has stimulated intense curiosity and speculation about their regulation and function. Research over the past three decades has described an impressive mutability in dendritic-spine number and morphology under a variety of physiological circumstance...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/s0166-2236(00)01576-9
更新日期：2000-04-01 00:00:00
abstract：:Age-related hearing loss (ARHL) is a common problem for older adults, leading to communication difficulties, isolation, and cognitive decline. Recently, hearing loss has been identified as potentially the most modifiable risk factor for dementia. Listening in challenging situations, or when the auditory system is dama...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/j.tins.2020.07.005
更新日期：2020-10-01 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 myelinated axon provides a model in which it is possible to examine how various types of ion channels are incorporated into a membrane to form an excitable neuronal process. The available evidence now indicates that mammalian myelinated fibers contain a repertoire of physiologically active membrane molecules inclu...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/0166-2236(90)90068-l
更新日期：1990-02-01 00:00:00
abstract：:The discovery of genetic forms of Parkinson's disease (PD) has highlighted the importance of the autophagy/lysosomal and mitochondrial/oxidative stress pathways in disease pathogenesis. However, recently identified PD-linked genes, including DNAJC6 (auxilin), SYNJ1 (synaptojanin 1), and the PD risk gene SH3GL2 (endoph...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/j.tins.2018.11.001
更新日期：2019-02-01 00:00:00
abstract：:The principal ovarian estrogen, estradiol, and brain-derived neurotrophic factor (BDNF) have widespread effects on the CNS that have usually been studied independently. This article examines the similarities in the effects of estradiol and BDNF in the hippocampus, in light of the evidence that estradiol can induce BDN...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/j.tins.2004.12.005
更新日期：2005-02-01 00:00:00
abstract：:Glial fibrillary acidic protein (GFAP) is an intermediate filament (IF) III protein uniquely found in astrocytes in the central nervous system (CNS), non-myelinating Schwann cells in the peripheral nervous system (PNS), and enteric glial cells. GFAP mRNA expression is regulated by several nuclear-receptor hormones, gr...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/j.tins.2015.04.003
更新日期：2015-06-01 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：: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：:Progress in molecular genetics has enabled the dissection of several autosomal dominantly inherited forms of cerebrovascular disorders. Mutations in diverse genes might induce pathological changes in intracranial vessels, resulting in cerebral haemorrhages and ischaemic strokes. Such pathologies, however, might also r...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/s0166-2236(00)01836-1
更新日期：2001-07-01 00:00:00
abstract：:Although signs of empathy have now been well documented in non-human primates, only during the past few years have systematic observations suggested that a primal form of empathy exists in rodents. Thus, the study of empathy in animals has started in earnest. Here we review recent studies indicating that rodents are a...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/j.tins.2013.04.009
更新日期：2013-08-01 00:00:00
abstract：:Many behavioral responses are completed too quickly for the underlying sensory processes to rely on estimation of neural firing rates over extended time windows. Theoretically, first-spike times could underlie such rapid responses, but direct evidence has been lacking. Such evidence has now been uncovered in the human...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/j.tins.2004.10.010
更新日期：2005-01-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is a lethal disease that is characterized by the relentless death of motoneurons. Mutations to Cu-Zn superoxide dismutase (SOD), though occurring in just 2-3% of individuals with ALS, remain the only proven cause of the disease. These mutations structurally weaken SOD, which indirec...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/s0166-2236(00)01981-0
更新日期：2001-11-01 00:00:00
abstract：:Adaptation to the ever-changing world is critical for survival, and our brains are particularly tuned to remember events that differ from previous experiences. Novel experiences induce dopamine release in the hippocampus, a process which promotes memory persistence. While axons from the ventral tegmental area (VTA) we...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/j.tins.2018.10.002
更新日期：2019-02-01 00:00:00
abstract：:In monkeys, the rostral part of ventral premotor cortex (area F5) contains neurons that discharge, both when the monkey grasps or manipulates objects and when it observes the experimenter making similar actions. These neurons (mirror neurons) appear to represent a system that matches observed events to similar, intern...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/s0166-2236(98)01260-0
更新日期：1998-05-01 00:00:00
abstract：:Cell replacement therapy has been proposed as a means to replace lost dopaminergic neurons in Parkinson's disease (PD). In most studies, the transplanted cells have been placed within the target site, the striatum, and not within the lesioned site, the substantia nigra, as the adult nigrostriatal pathway was thought t...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/j.tins.2011.01.003
更新日期：2011-03-01 00:00:00
abstract：:A century after the discovery of acetylcholine (ACh), we recognize both ACh receptors, transporters, and synthesizing and degrading enzymes and regulators of their expression as contributors to cognition, metabolism, and immunity. Recent discoveries indicate that pre- and post-transcriptional ACh signaling controllers...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/j.tins.2015.05.007
更新日期：2015-07-01 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：:How the brain becomes lateralized is poorly understood. By contrast, much is known about molecular cues that specify the left-right axis of the body, fashioning the asymmetric morphology and positioning of the visceral organs. In zebrafish, the Nodal signaling pathway functions in visceral asymmetry and also in the em...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/S0166-2236(03)00129-2
更新日期：2003-06-01 00:00:00
abstract：:Priming is the process by which vesicles become available for fusion at nerve terminals and is modulated by numerous proteins and second messengers. One of the prominent members of this diverse family is tomosyn. Tomosyn has been identified as a syntaxin-binding protein; it inhibits vesicle priming, but its mode of ac...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/j.tins.2009.01.004
更新日期：2009-05-01 00:00:00
abstract：:Fear is an adaptive response to recognition of a potentially dangerous event. Glucocorticoids are essential for maintaining a wide variety of behavioral events by their regulation of numerous genes; one such gene encodes corticotrophin-releasing hormone (CRH). CRH is involved in diverse behavioral responses to changin...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/j.tins.2005.09.009
更新日期：2005-12-01 00:00:00
abstract：:Intracellular Ca2+ initiates physiological events as diverse as gene transcription, muscle contraction, cell division and exocytosis. Predictably, the metabolic machinery that elicits and responds to changes in intracellular Ca2+ is correspondingly heterogeneous. This review focuses on one element of this complex web ...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：
更新日期：1995-02-01 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：:Speakers of different languages think about time differently in accordance with the spatial metaphors common in their languages. Furthermore, learning new spatial metaphors in language instills new non-linguistic representations of time, suggesting that language can play a causal role in constructing mental timelines....
journal_title：Trends in neurosciences
pub_type： 杂志文章
doi：10.1016/j.tins.2018.08.004
更新日期：2018-10-01 00:00:00
abstract：:The ACh hydrolyzing enzyme acetylcholinesterase (AChE) is a combinatorial series of proteins with variant N and C termini generated from alternate promoter usage and 3' alternative splicing. Neuronal AChE variants show indistinguishable enzymatic activity yet differ in their expression, multimeric assembly and membran...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/j.tins.2006.02.005
更新日期：2006-04-01 00:00:00
abstract：:Patients suffering from severe depression often show an increased activity of the hypothalamic-pituitary-adrenocortical (HPA) system, a premature escape from the cortisol suppressant action of dexamethasone, and a number of other neuroendocrine changes. This might be explained by defective glucocorticoid feedback inhi...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/0166-2236(95)93942-q
更新日期：1995-01-01 00:00:00
abstract：:In contrast to innocuous stimuli, which only have transient effects when applied to the body surface, noxious stimuli generate persistent changes in the nervous system. This nociceptive memory manifests itself most prominently as a post-injury sensitization where, after tissue damage, the avoidance reaction and pain t...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/0166-2236(91)90024-o
更新日期：1991-02-01 00:00:00
abstract：:As we learn more about the functional expression of nicotinic receptors in specific brain regions such as the hippocampus, intriguing interactions are being uncovered at the cellular and circuit levels. Recent work from John Dani's laboratory provides important insights into how nicotinic receptors can modify hippocam...
journal_title：Trends in neurosciences
pub_type： 杂志文章,评审
doi：10.1016/s0166-2236(00)02127-5
更新日期：2002-04-01 00:00:00
abstract：:Advances in understanding the biology of neurotrophic factors and their signaling pathways have provided important insights into the normal growth, differentiation and maintenance of neurons. Stimulated by neuropathological observations and genetic discoveries, studies in cell and animal models of neurodegenerative di...
journal_title：Trends in neurosciences
pub_type： 杂志文章
doi：10.1016/S0166-2236(02)00038-3
更新日期：2003-02-01 00:00:00
