Abstract:
:Alzheimer's disease (AD) is the most common type of senile dementia, characterized by neurofibrillary tangle and amyloid plaque in brain pathology. Major efforts in AD drug were devoted to the interference with the production and accumulation of amyloid-β peptide (Aβ), which plays a causal role in the pathogenesis of AD. Aβ is generated from amyloid precursor protein (APP), by consecutive cleavage by β-secretase and γ-secretase. Therefore, β-secretase and γ-secretase inhibition have been the focus for AD drug discovery efforts for amyloid reduction. Here, we review β-secretase inhibitors and γ-secretase inhibitors/modulators, and their efficacies in clinical trials. In addition, we discussed the novel concept of specifically targeting the γ-secretase substrate APP. Targeting amyloidogenic processing of APP is still a fundamentally sound strategy to develop disease-modifying AD therapies and recent advance in γ-secretase/APP complex structure provides new opportunities in designing selective inhibitors/modulators for AD.
journal_name
Front Mol Neuroscijournal_title
Frontiers in molecular neuroscienceauthors
Zhao J,Liu X,Xia W,Zhang Y,Wang Cdoi
10.3389/fnmol.2020.00137subject
Has Abstractpub_date
2020-08-04 00:00:00pages
137issn
1662-5099journal_volume
13pub_type
杂志文章,评审abstract::Panx1 forms plasma membrane channels in brain and several other organs, including the inner ear. Biophysical properties, activation mechanisms and modulators of Panx1 channels have been characterized in detail, however the impact of Panx1 on auditory function is unclear due to conflicts in published results. To addres...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00379
更新日期:2017-11-28 00:00:00
abstract::Thiol groups can undergo numerous modifications, making cysteine a unique molecular switch. Cysteine plays structural and regulatory roles as part of proteins or glutathione, contributing to maintain redox homeostasis and regulate signaling within and amongst cells. Not surprisingly therefore, cysteines are associated...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2017.00167
更新日期:2017-06-06 00:00:00
abstract::Inter-relationships ordinarily exist between mRNA expression of GABA(A) subunits in the frontopolar cortex (FPC) of individuals that had died suddenly from causes other than suicide. However, these correlations were largely absent in persons that had died by suicide. In the present investigation, these findings were e...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/neuro.02.003.2010
更新日期:2010-03-29 00:00:00
abstract::Although several agents have been identified to provide therapeutic benefits in Huntington disease (HD), the number of conventionally used treatments remains limited and only symptomatic. Thus, it is plausible that the need to identify new therapeutic targets for the development of alternative and more effective treat...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00100
更新日期:2019-04-24 00:00:00
abstract::The low-density lipoprotein receptor-related protein 1, LRP1, interacts with APP and affects its processing. This is assumed to be mostly caused by the impact of LRP1 on APP endocytosis. More recently, also an interaction of APP and LRP1 early in the secretory pathway was reported whereat retention of LRP1 in the ER l...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00118
更新日期:2017-04-27 00:00:00
abstract::It is widely accepted that glutamate is the most important excitatory neurotransmitter in the central nervous system (CNS). However, there is also a large amount of glutamate in the blood. Generally, the concentration gradient of glutamate between intraparenchymal and blood environments is stable. However, this gradie...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2017.00400
更新日期:2017-12-05 00:00:00
abstract::Aging cognitive decline has been associated to impairment of the Hypothalamus Pituitary Adrenals (HPA) axis activity and a higher level of the systemic inflammation. However, little is known about the molecules driving this process at peripheral level. In addition, the cognitive function is to some extent modifiable w...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00233
更新日期:2017-07-24 00:00:00
abstract::The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) are major excitatory receptors that mediate fast neurotransmission in the mammalian brain. The surface expression of functional AMPARs is crucial for synaptic transmission and plasticity. AMPAR auxiliary subunits control ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00055
更新日期:2017-03-02 00:00:00
abstract::Increasing evidence highlighted the role of cancer stem cells (CSCs) in the development of tumor resistance to therapy, particularly in glioblastoma (GBM). Therefore, the development of new therapies, specifically directed against GBM CSCs, constitutes an important research avenue. Considering the extended range of ca...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2016.00107
更新日期:2016-10-27 00:00:00
abstract::Although second harmonic generation (SHG) microscopy provides unique imaging advantages for voltage imaging and other biological applications, genetically-encoded SHG chromophores remain relatively unexplored. SHG only arises from non-centrosymmetric media, so an anisotropic arrangement of chromophores is essential to...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2014.00093
更新日期:2014-11-27 00:00:00
abstract::Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is a neurodegenerative disorder caused by loss-of-function mutations in the cystatin B (CSTB) gene. Progression of the clinical symptoms in EPM1 patients, including stimulus-sensitive myoclonus, tonic-clonic seizures, and ataxia, are well described. How...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.570640
更新日期:2020-11-13 00:00:00
abstract::Transient global cerebral ischemia (tGCI) causes excessive release of glutamate from neurons. Astrocytic glutamate transporter-1 (GLT-1) and glutamine synthetase (GS) together play a predominant role in maintaining glutamate at normal extracellular concentrations. Though our previous studies reported the alleviation o...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00344
更新日期:2018-10-01 00:00:00
abstract::Microglia are the innate sentinels of the central nervous system (CNS) and are responsible for the homeostasis and immune defense of the CNS. Under the influence of the local environment and cell-cell interaction, microglia exhibit a multidimensional and context-dependent phenotypes that can be cytotoxic and neuroprot...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2018.00158
更新日期:2018-05-14 00:00:00
abstract::Neuronal identity is generated by the cell-surface expression of clustered protocadherin (Pcdh) isoforms. In mice, 58 isoforms from three gene clusters, Pcdhα, Pcdhβ, and Pcdhγ, are differentially expressed in neurons. Since cis-heteromeric Pcdh oligomers on the cell surface interact homophilically with that in other ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00114
更新日期:2017-04-24 00:00:00
abstract::Using a high resolution in situ hybridization technique we have measured PIEZO1, PIEZO2, and TRPV1 transcripts in mouse dorsal root ganglion (DRG) neurons. Consistent with previous studies, PIEZO2 transcripts were highly expressed in DRG neurons of all sizes, including most notably the largest diameter neurons implica...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00178
更新日期:2019-07-19 00:00:00
abstract::[This corrects the article on p. 257 in vol. 10, PMID: 28855859.]. ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,已发布勘误
doi:10.3389/fnmol.2017.00392
更新日期:2017-11-20 00:00:00
abstract::Ischemic stroke is one of the most common causes of death and disability worldwide. Neuroinflammation is a major pathological event involved in the process of ischemic injury and repair. In particular, microglia play a dual role in neuroinflammation. During the acute phase of stroke onset, M2 microglia are the dominan...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2020.612439
更新日期:2021-01-07 00:00:00
abstract::Many genes controlling neuronal development also regulate adult neurogenesis. We investigated in vivo the effect of Sonic hedgehog (Shh) signaling activation on patterning and neurogenesis of the hippocampus and behavior of Patched1 (Ptch1) heterozygous mice (Ptch1+/- ). We demonstrated for the first time, that Ptch1+...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00168
更新日期:2018-05-23 00:00:00
abstract::Unbiased "omics" techniques, such as next generation RNA-sequencing, can provide entirely novel insights into biological systems. However, cellular heterogeneity presents a significant barrier to analysis and interpretation of these datasets. The neurons of the dorsal root ganglia (DRG) are an important model for stud...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2014.00087
更新日期:2014-11-11 00:00:00
abstract::Lipid metabolism is drastically dysregulated in amyotrophic lateral sclerosis and impacts prognosis of patients. Animal models recapitulate alterations in the energy metabolism, including hypermetabolism and severe loss of adipose tissue. To gain insight into the molecular mechanisms underlying disease progression in ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00433
更新日期:2018-01-04 00:00:00
abstract::Medical marijuana is increasingly prescribed as an analgesic for a growing number of indications, amongst which terminal cancer and multiple sclerosis. However, the mechanistic aspects and properties of cannabis remain remarkably poorly characterized. In this study we aimed to investigate the immune-cell modulatory pr...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00014
更新日期:2017-01-24 00:00:00
abstract::Connexin channels play numerous essential roles in virtually every organ by mediating solute exchange between adjacent cells, or between cytoplasm and extracellular milieu. Our understanding of the structure-function relationship of connexin channels relies on X-ray crystallographic data for human connexin 26 (hCx26) ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00170
更新日期:2018-05-31 00:00:00
abstract::γ-Aminobutyric acid type A receptors (GABAARs) mediate the majority of fast synaptic inhibition in the central nervous system (CNS). GABAARs belong to the Cys-loop superfamily of pentameric ligand-gated ion channels (pLGIC) and are assembled from 19 different subunits. As dysfunctional GABAergic neurotransmission mani...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00191
更新日期:2019-08-07 00:00:00
abstract::Intracerebral hemorrhage (ICH) is a subtype of stroke with highest mortality and morbidity. We have previously demonstrated that dipotassium bisperoxo (picolinato) oxovanadate (V), (bpV[pic]) inhibits phosphatase and tensin homolog (PTEN) and activates extracellular signal-regulated kinase (ERK)1/2. In this study, we ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00281
更新日期:2019-12-05 00:00:00
abstract::The bioactive lipid sphingosine-1-phosphate (S1P) is an important regulator in the nervous system. Here, we explored the role of S1P and its receptors in vitro and in preclinical models of peripheral nerve regeneration. Adult sensory neurons and motor neuron-like cells were exposed to S1P in an in vitro assay, and vir...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00317
更新日期:2017-10-10 00:00:00
abstract::Transcription factors regulate multiple processes during brain development and in the adult brain, from brain patterning to differentiation and maturation of highly specialized neurons as well as establishing and maintaining the functional neuronal connectivity. The members of the zinc-finger transcription factor fami...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2020.00051
更新日期:2020-04-08 00:00:00
abstract::Cryptochromes (CRYs) are a class of flavoproteins that sense blue light. In animals, CRYs are expressed in the eyes and in the clock neurons that control sleep/wake cycles and are implied in the generation and/or entrainment of circadian rhythmicity. Moreover, CRYs are sensing magnetic fields in insects as well as in ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00238
更新日期:2018-07-18 00:00:00
abstract::The brain is complex and heterogeneous. Even though numerous independent studies indicate cortical hyperexcitability as a potential contributor to amyotrophic lateral sclerosis (ALS) pathology, the mechanisms that are responsible for upper motor neuron (UMN) vulnerability remain elusive. To reveal the electrophysiolog...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.00073
更新日期:2020-05-19 00:00:00
abstract::The polycomb group proteins (PcGs) are a group of epigenetic factors associated with gene silencing. They are found in several families of multiprotein complexes, including polycomb repressive complex 2 (PRC2). EZH2, EED and SUZ12 form the core components of the PRC2 complex, which is responsible for the mono, di- and...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00076
更新日期:2019-04-09 00:00:00
abstract::Long-term potentiation (LTP) and long-term depression (LTD) are two major forms of synaptic plasticity that are widely accepted as cellular mechanisms involved in learning and memory. Metaplasticity is a process whereby modifications in synaptic processes shift the threshold for subsequent plasticity. While metaplasti...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00322
更新日期:2020-01-24 00:00:00