Abstract：
:Twenty years ago, Wolfe, Xia, and Selkoe identified two aspartate residues in Alzheimer's presenilin protein that constitute the active site of the γ-secretase complex. Mutations in the genes encoding amyloid precursor protein (APP) or presenilin (PS) cause early onset familial Alzheimer's disease (AD), and sequential cleavages of the APP by β-secretase and γ-secretase/presenilin generate amyloid β protein (Aβ), the major component of pathological hallmark, neuritic plaques, in brains of AD patients. Therapeutic strategies centered on targeting γ-secretase/presenilin to reduce amyloid were implemented and led to several high profile clinical trials. This review article focuses on the studies of γ-secretase and its inhibitors/modulators since the discovery of presenilin as the γ-secretase. While a lack of complete understanding of presenilin biology renders failure of clinical trials, the lessons learned from some γ-secretase modulators, while premature for human testing, provide new directions to develop potential therapeutics. Imbalanced Aβ homeostasis is an upstream event of neurodegenerative processes. Exploration of γ-secretase modulators for their roles in these processes is highly significant, e.g., decreasing neuroinflammation and levels of phosphorylated tau, the component of the other AD pathological hallmark, neurofibrillary tangles. Agents with excellent human pharmacology hold great promise in suppressing neurodegeneration in pre-symptomatic or early stage AD patients.
journal_name
Neurosci Lettjournal_title
Neuroscience lettersauthors
Xia Wdoi
10.1016/j.neulet.2019.02.011subject
Has Abstractpub_date
2019-05-14 00:00:00pages
162-169eissn
0304-3940issn
1872-7972pii
S0304-3940(19)30094-1journal_volume
701pub_type
杂志文章,评审abstract：:This investigation was designed to determine the responses of neurons in the posterior group of nuclei (PO) to tooth pulp stimulation. Eighteen tooth pulp-driven (TPD) neurons were recorded in 9 cats anesthetized with nitrous oxide and halothane, 14 of them in the medial part (POM) and the remainder in the lateral par...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(88)90091-2
更新日期：1988-11-11 00:00:00
abstract：:UBB+1 protein is an aberrant ubiquitin associated with progressive supranuclear palsy (PSP). It leads to proteasome inhibition, heat-shock protein (HSP) expression and apoptosis in cell cultures. Despite UBB+1 polyubiquitination (an indication of proteasome inhibition), we demonstrate that UBB+1 and HSP40/HSP70 immuno...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2003.12.127
更新日期：2004-04-08 00:00:00
abstract：:Rat myotubes were cultured with embryonic mouse spinal cord explants. After 4 days of co-culture, (miniature) endplate potentials, (M)EPPs, could be detected in 20-40% of the nerve-contacted myotubes. Polyclonal antibodies against the neural cell adhesion molecule N-CAM and monoclonal antibodies to its L2/HNK-1 carboh...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(87)90368-5
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abstract：:An optimized clinical functional magnetic resonance imaging (fMRI) protocol with a total scanning time of 8 min is presented that localizes Broca's and Wernicke's areas robustly and determines hemispheric dominance. Language function was visualized using two different sentence generation (SG) and word generation (WG) ...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/s0304-3940(03)00561-5
更新日期：2003-07-31 00:00:00
abstract：:Antipsychotic drugs remain the mainstay of pharmacotherapy for schizophrenia. As there are large individual variations in efficacy and side-effects of antipsychotic drugs, there is a strong demand for personalized medication to treat schizophrenia. Pharmacogenetic research into antipsychotic drugs has examined a numbe...
journal_title：Neuroscience letters
pub_type： 杂志文章,评审
doi：10.1016/j.neulet.2018.10.015
更新日期：2020-05-01 00:00:00
abstract：:The perception of visual motion is dependent on a set of occipitotemporal regions that are readily accessible to neuromodulation. The current study tested if paired-pulse Transcranial Magnetic Stimulation (ppTMS) could modulate motion perception by stimulating the occipital cortex as participants viewed near-threshold...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2020.135022
更新日期：2020-06-21 00:00:00
abstract：:Freezing is one of the most widely recognized defensive reactions to approaching threats in animals. Here we tested whether the same stimuli can elicit freeze-like responses in healthy humans as well. We used a modified version of the two-frame apparent motion paradigm, in which both size and location of a stimulus wi...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2013.12.038
更新日期：2014-02-21 00:00:00
abstract：:To investigate injury-induced alterations of purinergic P2Y receptor-mediated calcium responses in glial (Müller) cells of the rabbit retina, neural retinae were experimentally detached from the pigment epithelium. The ATP-evoked calcium responses were recorded in the endfeet of glial cells at the vitread surface of r...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/s0304-3940(02)01402-7
更新日期：2003-02-27 00:00:00
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journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2014.06.059
更新日期：2014-08-22 00:00:00
abstract：:Amyloid beta (Aβ) is the main component of plaques, the central neuropathological hallmark in Alzheimer's disease (AD). Aβ is derived from the amyloid precursor protein (APP) by β- and γ-secretase-mediated cleavages. A large number of Aβ peptides are found in cerebrospinal fluid and these peptides are produced in spec...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2014.04.041
更新日期：2014-06-24 00:00:00
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journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2004.08.044
更新日期：2004-11-16 00:00:00
abstract：:Protein synthesis is required for long-lasting synaptic plasticity. We examined the time-dependent changes in protein expression that occurred in the hippocampus during synaptic plasticity using two-dimensional gel electrophoresis followed by mass spectrometry. The levels of 15 proteins were significantly changed in m...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2013.07.036
更新日期：2013-10-25 00:00:00
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journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/s0304-3940(01)01825-0
更新日期：2001-06-08 00:00:00
abstract：:Our previous study demonstrated that successive electroacupuncture (EA) at ST36 acupoint reduces IgE production in BALB/c mice immunized with 2,4-dinitrophenylated keyhole limpet protein (DNP-KLH) by suppression of the Th2 cell lineage development. Here, we report that pretreatment of phentolamine (alpha-adrenoceptor ...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2007.07.002
更新日期：2007-08-16 00:00:00
abstract：:Small iontophoretic applications of wheat germ agglutinin-conjugated to horseradish peroxidase have been used to simultaneously observe, in the rat, the afferent and efferent connections of small parabrachial subregions in the same animal. The results demonstrate that a restricted region centered on the external porti...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(89)90664-2
更新日期：1989-05-22 00:00:00
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journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(95)11585-k
更新日期：1995-05-26 00:00:00
abstract：BACKGROUND:Brain function relies on the capacity of neurons to locally modulate each other at the level of synapses. Therefore, the exosomal pathway may constitute a well-designed mechanism for local and systemic interneuronal transfer of information within functional brain networks. Exosomes bind to and are endocytose...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2020.134774
更新日期：2020-04-01 00:00:00
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journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2008.09.004
更新日期：2008-11-14 00:00:00
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journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/s0304-3940(99)00943-x
更新日期：2000-02-04 00:00:00
abstract：:Hibernation in mammals is a whole-body phenotype that involves profound reductions in oxygen consumption, metabolic reactions, core body temperature, neural activity and heart rate. An important aspect of mammalian hibernation is the ability to reverse this state of hypothermic torpor by rewarming and subsequent arous...
journal_title：Neuroscience letters
pub_type： 杂志文章,评审
doi：10.1016/j.neulet.2018.11.059
更新日期：2019-03-23 00:00:00
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journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2014.07.008
更新日期：2014-09-05 00:00:00
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journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(85)90210-1
更新日期：1985-08-16 00:00:00
abstract：:We have used Lucifer Yellow for histological tracing of displaced amacrine cells within the ganglion cell layer (GCL) during the embryonic development of the chicken retina. Incubating whole eyes in the dye leads to bright staining of all displaced amacrine cells, whereas ganglion cells and glial cells are not stained...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(82)90099-4
更新日期：1982-08-16 00:00:00
abstract：:Activation of spinal astrocytes may contribute to neuropathic pain. Adjacent astrocytes can make direct communication through gap junctions formed by connexin 43 (Cx43) in the central nervous system. Yet, the role of spinal astroglial gap junctions in neuropathic pain is not fully understood. Since Cx43 is the connexi...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2014.03.004
更新日期：2014-04-30 00:00:00
abstract：:Immunohistochemical and biochemical investigations showed that significant protein nitration occurs in human gliomas, especially in grade IV glioblastomas at the level of astrocytes and oligodendrocytes and neurones. Enhanced alpha-tubulin immunoreactivity was co-present in the same elements in the glioblastomas. Prot...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2005.10.011
更新日期：2006-02-06 00:00:00
abstract：:The pathological changes occurring in a population of parvalbumin-like immunoreactive cerebral cortical interneurones in postmortem Alzheimer-type dementia brain tissue were determined by double staining cerebral cortical sections for parvalbumin, tau and/or calpain-like immunoreactivities. By counting the number of d...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(91)90764-k
更新日期：1991-07-08 00:00:00
abstract：:The neurotoxin 6-hydroxydopamine (6-OHDA) is used to induce dopaminergic cell death, resulting in insufficient striatal dopamine content in the basal ganglia and motor dysfunction typical of Parkinson's disease. Dopamine induces release of the neuropeptide substance P (SP) within the substantia nigra, whereas SP is ab...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2010.06.057
更新日期：2010-08-30 00:00:00
abstract：:Responses of single neurones to vibrissal stimulation and to the iontophoretically applied putative neurotransmitters, L-glutamate and L-aspartate, were recorded in the trigeminal nucleus caudalis of the rat. Vibrissal responses were unaffected by the specific N-methyl-D-aspartate receptor antagonist, D-alpha-aminoadi...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(81)90085-9
更新日期：1981-03-10 00:00:00
abstract：:The myelin oligodendrocyte glycoprotein (MOG) is a minor CNS myelin-specific protein that is an important candidate autoantigen in multiple sclerosis. We now report that MOG mRNA transcripts are present in the peripheral nervous system of rodents and primates at levels approximately ten-fold lower than in brain as dem...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/s0304-3940(03)00899-1
更新日期：2003-10-30 00:00:00
abstract：:Chewing and walking are two oscillatory behaviors performed on an everyday basis. The current study examined the impact chewing at different speeds (i.e. fast, slow, preferred) had on walking performance for fifteen young healthy adults (23.2 + 4.2 years) and fifteen healthy older participants (66.5 + 3.2 years). Chew...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2019.01.016
更新日期：2019-04-17 00:00:00
