Presenilins: molecular switches between proteolysis and signal transduction.

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 Neurosci

journal_title

Trends in neurosciences

authors

Annaert W,De Strooper B

doi

10.1016/s0166-2236(99)01455-1

subject

Has Abstract

pub_date

1999-10-01 00:00:00

pages

439-43

issue

10

eissn

0166-2236

issn

1878-108X

pii

S0166-2236(99)01455-1

journal_volume

22

pub_type

杂志文章,评审
  • Getting the most out of noise in the central nervous system.

    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

    authors: Traynelis SF,Jaramillo F

    更新日期:1998-04-01 00:00:00

  • Auditory thalamocortical transformation: structure and function.

    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

    authors: Winer JA,Miller LM,Lee CC,Schreiner CE

    更新日期:2005-05-01 00:00:00

  • Regulation of neuronal function by calcium.

    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

    authors: Kennedy MB

    更新日期:1989-11-01 00:00:00

  • Facilitation, augmentation and potentiation at central synapses.

    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

    authors: Thomson AM

    更新日期:2000-07-01 00:00:00

  • Dendritic mechanisms controlling spike-timing-dependent synaptic plasticity.

    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

    authors: Kampa BM,Letzkus JJ,Stuart GJ

    更新日期:2007-09-01 00:00:00

  • Ion Channels and Receptors as Determinants of Microglial Function.

    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

    authors: Izquierdo P,Attwell D,Madry C

    更新日期:2019-04-01 00:00:00

  • Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action.

    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

    authors: Di Marzo V,Melck D,Bisogno T,De Petrocellis L

    更新日期:1998-12-01 00:00:00

  • Diversity of inhibitory neurotransmission through GABA(A) receptors.

    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

    authors: Mody I,Pearce RA

    更新日期:2004-09-01 00:00:00

  • What mechanisms coordinate leg movement in walking arthropods?

    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

    authors: Cruse H

    更新日期:1990-01-01 00:00:00

  • Actin and the agile spine: how and why do dendritic spines dance?

    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

    authors: Halpain S

    更新日期:2000-04-01 00:00:00

  • A neuroendocrine mechanism for sustaining fear.

    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

    authors: Schulkin J,Morgan MA,Rosen JB

    更新日期:2005-12-01 00:00:00

  • Glial cells aid axonal target selection.

    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

    authors: Pielage J,Klämbt C

    更新日期:2001-08-01 00:00:00

  • Memory traces in spinal cord.

    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

    authors: Wolpaw JR,Carp JS

    更新日期:1990-04-01 00:00:00

  • Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype?

    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

    authors: Gerlai R

    更新日期:1996-05-01 00:00:00

  • A vitamin for the brain.

    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

    authors: Shearer KD,Stoney PN,Morgan PJ,McCaffery PJ

    更新日期:2012-12-01 00:00:00

  • Drosophila Mechanosensory Transduction.

    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

    authors: Hehlert P,Zhang W,Göpfert MC

    更新日期:2020-11-27 00:00:00

  • The thrifty lipids: endocannabinoids and the neural control of energy conservation.

    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

    authors: DiPatrizio NV,Piomelli D

    更新日期:2012-07-01 00:00:00

  • A rationale for the structure of color space.

    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

    authors: Lotto RB,Purves D

    更新日期:2002-02-01 00:00:00

  • Genes required for specifying cell fates in Drosophila embryonic sensory nervous system.

    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

    authors: Jan YN,Jan LY

    更新日期:1990-12-01 00:00:00

  • Noisy Synaptic Conductance: Bug or a Feature?

    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

    authors: Rusakov DA,Savtchenko LP,Latham PE

    更新日期:2020-06-01 00:00:00

  • The c-Jun transcription factor--bipotential mediator of neuronal death, survival and regeneration.

    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

    authors: Herdegen T,Skene P,Bähr M

    更新日期:1997-05-01 00:00:00

  • Axonal flip-flops and oscillators.

    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

    authors: Baker MD

    更新日期:2000-11-01 00:00:00

  • The fundamental role of memory in olfactory perception.

    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

    authors: Wilson DA,Stevenson RJ

    更新日期:2003-05-01 00:00:00

  • Language within our grasp.

    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

    authors: Rizzolatti G,Arbib MA

    更新日期:1998-05-01 00:00:00

  • The behaving brain of a fly.

    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

    authors: Ferrús A,Canal I

    更新日期:1994-11-01 00:00:00

  • Neural Circuits for Goal-Directed Sensorimotor Transformations.

    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

    authors: Crochet S,Lee SH,Petersen CCH

    更新日期:2019-01-01 00:00:00

  • Abnormal cognition and behavior in preterm neonates linked to smaller brain volumes.

    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

    authors: Bhutta AT,Anand KJ

    更新日期:2001-03-01 00:00:00

  • Organizing pains.

    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

    authors: Garry EM,Fleetwood-Walker SM

    更新日期:2004-06-01 00:00:00

  • Sesquicentenary of the birthday of Santiago Ramón y Cajal, the father of modern neuroscience.

    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

    authors: DeFelipe J

    更新日期:2002-09-01 00:00:00

  • Chromatin Regulation of Neuronal Maturation and Plasticity.

    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

    authors: Gallegos DA,Chan U,Chen LF,West AE

    更新日期:2018-05-01 00:00:00