Abstract:
:Mis-sense mutations of presenilin 1 increase the release of amyloidogenic peptide from amyloid precursor protein (APP) and are a major cause of familial Alzheimer's Disease. Loss-of-function mutations of presenilins in the mouse, Caenorhabditis elegans and Drosophila result in severe developmental defects caused by disturbed Notch signalling. Recent studies suggest that the diverse biological roles of presenilin 1 can be explained at the molecular level by its role in the proteolytic cleavage of the integral membrane domains of Notch and APP. This cleavage is a central switch in Notch signalling, while, for APP, its physiological role remains elusive. Evidence that presenilin 1 itself has catalytic properties could explain many of the biological and biochemical alterations caused by presenilin-1 deficiency or clinical mutations in presenilin 1. However, as presenilins reside in the endoplasmic reticulum and the cleavage of Notch and APP is believed to occur close to the cell membrane, the scientific field now faces a 'spatial paradox'.
journal_name
Trends Neuroscijournal_title
Trends in neurosciencesauthors
Annaert W,De Strooper Bdoi
10.1016/s0166-2236(99)01455-1subject
Has Abstractpub_date
1999-10-01 00:00:00pages
439-43issue
10eissn
0166-2236issn
1878-108Xpii
S0166-2236(99)01455-1journal_volume
22pub_type
杂志文章,评审abstract::Rather than merely a nuisance, noise in biological systems is a useful property. Before patch-clamp methods were invented, analysis of membrane current noise provided the first solid, if indirect, evidence for the existence of ion-conducting pores with discrete conductance levels. Although supplanted by single-channel...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(98)01238-7
更新日期:1998-04-01 00:00:00
abstract::Communicative, predatory, and reproductive behaviors rely on the auditory thalamocortical system, a key nexus that combines, transforms, and distributes virtually all acoustic information relevant to survival. The rules of connectivity for this complex network, both anatomically and functionally, are only beginning to...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2005.03.009
更新日期:2005-05-01 00:00:00
abstract::In the classical picture of brain function, electrical impulses are initiated in sensory organs and spread rapidly down axons, jumping synaptic clefts by neurochemical transmission. Patterns of electrical activity generated in this way integrate information throughout the brain and result in coordinated motor output. ...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/0166-2236(89)90089-1
更新日期:1989-11-01 00:00:00
abstract::Release probability (P) appears to be a major factor that influences the pattern of transmitter release. At cortical pyramidal axon inputs onto different classes of target cells, very different release patterns are observed, patterns that correlate with release probability. Simplistically, 'low P' synapses display fac...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(00)01580-0
更新日期:2000-07-01 00:00:00
abstract::The ability of neurons to modulate the strength of their synaptic connections has been shown to depend on the relative timing of pre- and postsynaptic action potentials. This form of synaptic plasticity, called spike-timing-dependent plasticity (STDP), has become an attractive model for learning at the single-cell lev...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2007.06.010
更新日期:2007-09-01 00:00:00
abstract::Microglia provide immune surveillance of the CNS. They display diverse behaviors, including nondirectional and directed motility of their processes, phagocytosis of targets such as dying neurons or superfluous synapses, and generation of reactive oxygen species (ROS) and cytokines. Many of these functions are mediated...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2018.12.007
更新日期:2019-04-01 00:00:00
abstract::The existence of an endogenous cannabinoid system was demonstrated conclusively with the discovery of endogenous brain constituents capable of activating the cannabinoid receptors functionally. These compounds are synthesized by neuronal cells and inactivated through re-uptake and enzymatic hydrolysis by both neurons ...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(98)01283-1
更新日期:1998-12-01 00:00:00
abstract::In the brain, highly connected and heterogeneous GABAergic cells are crucial in controling the activity of neuronal networks. They accomplish this task by communicating through remarkably diverse sets of inhibitory processes, the complexity of which is reflected by the variety of interneuron classification schemes pro...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2004.07.002
更新日期:2004-09-01 00:00:00
abstract::The construction of artificial walking machines has been a challenging task for engineers for several centuries. Advances in computer technology have stimulated this research in the past two decades, and enormous progress has been made, particularly in recent years. Nevertheless, in comparing the walk of a six-legged ...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/0166-2236(90)90057-h
更新日期:1990-01-01 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::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::A key problem in developmental neurobiology is how axons home in on their correct target tissue and establish the correct synaptic contacts. Recent work shows that in the developing Drosophila visual system a population of distinct lamina glial cells ensures correct target layer selection of retinal axons. In the abse...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(00)01861-0
更新日期:2001-08-01 00:00:00
abstract::The complexity and inaccessibility of the vertebrate CNS impede the localization and description of memory traces and the definition of the processes that create them. Recent work has shown that the spinal stretch reflex (SSR), which is produced by a monosynaptic two-neuron pathway, can be operantly conditioned, and t...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/0166-2236(90)90005-u
更新日期:1990-04-01 00:00:00
abstract::Gene targeting to create null mutations in mice is a powerful new tool in biology which will allow the molecular dissection of complex phenotypes such as mammalian brain function, and learning and memory. However, the attempt to interpret the phenotypical changes which arise in null-mutant mice is subject to several c...
journal_title:Trends in neurosciences
pub_type: 杂志文章
doi:10.1016/s0166-2236(96)20020-7
更新日期:1996-05-01 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::Mechanosensation in Drosophila relies on sensory neurons transducing mechanical stimuli into ionic currents. The molecular mechanisms of this transduction are in the process of being revealed. Transduction relies on mechanogated ion channels that are activated by membrane stretch or the tension of force-conveying teth...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2020.11.001
更新日期:2020-11-27 00:00:00
abstract::The 'thrifty gene hypothesis' posits that evolution preferentially selects physiological mechanisms that optimize energy storage to increase survival under alternating conditions of abundance and scarcity of food. Recent experiments suggest that endocannabinoids - a class of lipid-derived mediators that activate canna...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2012.04.006
更新日期:2012-07-01 00:00:00
abstract::The colors perceived by humans in response to light stimuli are generally described in terms of four color categories (reds, greens, blues and yellows), the members of which are systematically arrayed around gray. This broadly accepted description of color sensation differs fundamentally from the light that induces it...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(02)02059-3
更新日期:2002-02-01 00:00:00
abstract::The nervous system contains a diverse group of cells. Specification of the correct cell fate is obviously important for the proper function of the nervous system, yet how are the fates of different neurons determined during development? Very little is known about the underlying molecular mechanisms used in the mammali...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/0166-2236(90)90083-m
更新日期:1990-12-01 00:00:00
abstract::More often than not, action potentials fail to trigger neurotransmitter release. And even when neurotransmitter is released, the resulting change in synaptic conductance is highly variable. Given the energetic cost of generating and propagating action potentials, and the importance of information transmission across s...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2020.03.009
更新日期:2020-06-01 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::The strange and unpleasant sensations (paraesthesiae) or asynchronous motor-unit activation (fasciculation) that result from a period of limb ischaemia are examples of ectopic discharge in peripheral nerves. Ectopic activity also results from demyelination and is associated with serious neurological conditions, such a...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(00)01645-3
更新日期:2000-11-01 00:00:00
abstract::Current emphasis on odorant physiochemical features as the basis for perception largely ignores the synthetic and experience-dependent nature of olfaction. Olfaction is synthetic, as mammals have only limited ability to identify elements within even simple odor mixtures. Furthermore, olfaction is experience-bound, as ...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/S0166-2236(03)00076-6
更新日期:2003-05-01 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::The use of Drosophila as a suitable system to answer behavioural questions is usually based on the availability of mutant phenotypes. Indeed, the 'single-gene' approach to behaviour was a very illuminating strategy in practical and conceptual terms, and served to prove that the genetic mechanisms sustaining behaviour ...
journal_title:Trends in neurosciences
pub_type: 杂志文章
doi:10.1016/0166-2236(94)90137-6
更新日期:1994-11-01 00:00:00
abstract::Precisely wired neuronal circuits process sensory information in a learning- and context-dependent manner in order to govern behavior. Simple sensory decision-making tasks in rodents are now beginning to reveal the contributions of distinct cell types and brain regions participating in the conversion of sensory inform...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2018.08.011
更新日期:2019-01-01 00:00:00
abstract::Volumetric measurements of the brain regions in eight-year-old children indicate that the poor cognitive and behavioral outcomes noted in ex-preterm neonates are associated with reduced volumes of specific regions in the brain. Recent literature suggests that this reduction might result from enhanced apoptosis or exci...
journal_title:Trends in neurosciences
pub_type: 杂志文章
doi:10.1016/s0166-2236(00)01747-1
更新日期:2001-03-01 00:00:00
abstract::Chronic pain is sustained by central neuronal sensitization, with many similar characteristics irrespective of the type of injury incurred. Nevertheless, pain arising from nerve injury (neuropathic pain) is resistant to centrally acting analgesics, whereas inflammatory pain responds well. New research indicates that t...
journal_title:Trends in neurosciences
pub_type: 杂志文章
doi:10.1016/j.tins.2004.03.014
更新日期:2004-06-01 00:00:00
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::Neurons are dynamic cells that respond and adapt to stimuli throughout their long postmitotic lives. The structural and functional plasticity of neurons requires the regulated transcription of new gene products, and dysregulation of transcription in either the developing or adult brain impairs cognition. We discuss ho...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2018.02.009
更新日期:2018-05-01 00:00:00