Abstract：
:Alzheimer's disease (AD) is a neurodegenerative disease biochemically characterized by aberrant protein aggregation, including amyloid beta (Aβ) peptide accumulation. Protein aggregates in the cell are cleared by autophagy, a mechanism impaired in AD. To investigate the role of autophagy in Aβ pathology in vivo, we crossed amyloid precursor protein (APP) transgenic mice with mice lacking autophagy in excitatory forebrain neurons obtained by conditional knockout of autophagy-related protein 7. Remarkably, autophagy deficiency drastically reduced extracellular Aβ plaque burden. This reduction of Aβ plaque load was due to inhibition of Aβ secretion, which led to aberrant intraneuronal Aβ accumulation in the perinuclear region. Moreover, autophagy-deficiency-induced neurodegeneration was exacerbated by amyloidosis, which together severely impaired memory. Our results establish a function for autophagy in Aβ metabolism: autophagy influences secretion of Aβ to the extracellular space and thereby directly affects Aβ plaque formation, a pathological hallmark of AD.
journal_name
Cell Repjournal_title
Cell reportsauthors
Nilsson P,Loganathan K,Sekiguchi M,Matsuba Y,Hui K,Tsubuki S,Tanaka M,Iwata N,Saito T,Saido TCdoi
10.1016/j.celrep.2013.08.042subject
Has Abstractpub_date
2013-10-17 00:00:00pages
61-9issue
1issn
2211-1247pii
S2211-1247(13)00502-0journal_volume
5pub_type
杂志文章相关文献
Cell Reports文献大全abstract：:Amyotrophic lateral sclerosis (ALS) is a devastating disease that progresses from detachment of motor nerve terminals to complete muscle paralysis and lethal respiratory failure within 5 years of diagnosis. Genetic studies have linked mutations in several genes to ALS, and mice bearing mutations in SOD1 recapitulate h...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2012.08.004
更新日期：2012-09-27 00:00:00
abstract：:A central paradigm in the field of lymphocyte biology asserts that replicatively senescent memory T cells express the carbohydrate epitope CD57. These cells nonetheless accumulate with age and expand numerically in response to persistent antigenic stimulation. Here, we use in vivo deuterium labeling and ex vivo analys...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108501
更新日期：2020-12-15 00:00:00
abstract：:Mouse embryonic stem cells are dynamic and heterogeneous. For example, rare cells cycle through a state characterized by decondensed chromatin and expression of transcripts, including the Zscan4 cluster and MERVL endogenous retrovirus, which are usually restricted to preimplantation embryos. Here, we further character...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.08.087
更新日期：2016-09-27 00:00:00
abstract：:Macrophages exist predominantly in two distinct states, G0 and a G1-like state that is accompanied by phosphorylation of SAMHD1 at T592. Here, we demonstrate that Toll-like receptor 4 (TLR4) activation can potently induce G0 arrest and SAMHD1 antiretroviral activity by an interferon (IFN)-independent pathway. This pat...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.03.008
更新日期：2020-03-24 00:00:00
abstract：:Palmitoylation is a reversible post-translational lipid modification that facilitates vesicular transport and subcellular localization of modified proteins. This process is catalyzed by ZDHHC enzymes that are implicated in several neurological and neurodevelopmental disorders. Loss-of-function mutations in ZDHHC9 have...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.10.065
更新日期：2019-11-19 00:00:00
abstract：:Eosinophils mediate protection against filarial nematodes. Our results demonstrate that eosinophil extracellular traps (EETosis) are induced by microfilariae and infective L3 larvae of Litomosoides sigmodontis. These extracellular DNA traps inhibit microfilariae motility in a DNA- and contact-dependent manner in vitro...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108621
更新日期：2021-01-12 00:00:00
abstract：:Let-7 microRNAs (miRNAs) are critical regulators of animal development, stem cell differentiation, glucose metabolism, and tumorigenesis. Mammalian genomes contain 12 let-7 isoforms that suppress expression of a common set of target mRNAs. LIN28 proteins selectively block let-7 biogenesis in undifferentiated cells and...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.08.086
更新日期：2015-10-13 00:00:00
abstract：:Oct4 is an essential regulator of pluripotency in vivo and in vitro in embryonic stem cells, as well as a key mediator of the reprogramming of somatic cells into induced pluripotent stem cells. It is not known whether activation and/or repression of specific genes by Oct4 is relevant to these functions. Here, we show ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2011.12.002
更新日期：2012-02-23 00:00:00
abstract：:How mutations in glial fibrillary acidic protein (GFAP) cause Alexander disease (AxD) remains elusive. We generated iPSCs from two AxD patients and corrected the GFAP mutations to examine the effects of mutant GFAP on human astrocytes. AxD astrocytes displayed GFAP aggregates, recapitulating the pathological hallmark ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.09.083
更新日期：2018-10-23 00:00:00
abstract：:During development, neurons are constantly refining their connections in response to changes in activity. Experience-dependent plasticity is a key form of synaptic plasticity, involving changes in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) accumulation at synapses. Here, we report a critical...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.04.054
更新日期：2014-06-12 00:00:00
abstract：:Natural killer (NK) cells possess potent cytotoxic mechanisms that need to be tightly controlled. Here, we explored the regulation and function of GPR56/ADGRG1, an adhesion G protein-coupled receptor implicated in developmental processes and expressed distinctively in mature NK cells. Expression of GPR56 was triggered...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.04.053
更新日期：2016-05-24 00:00:00
abstract：:CELF6 is a CELF-RNA-binding protein, and thus part of a protein family with roles in human disease; however, its mRNA targets in the brain are largely unknown. Using cross-linking immunoprecipitation and sequencing (CLIP-seq), we define its CNS targets, which are enriched for 3' UTRs in synaptic protein-coding genes. ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108531
更新日期：2020-12-22 00:00:00
abstract：:Fragile X mental retardation protein (FMRP) promotes cyclic AMP (cAMP) signaling. Using an in vivo protein kinase A activity sensor (PKA-SPARK), we find that Drosophila FMRP (dFMRP) and human FMRP (hFMRP) enhance PKA activity in a central brain learning and memory center. Increasing neuronal PKA activity suppresses FM...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108266
更新日期：2020-10-13 00:00:00
abstract：:HIV-1 is transmitted between T cells through the release of cell-free particles and through cell-cell contact. Cell-to-cell transmission is more efficient than cell-free virus transmission, mediates resistance to immune responses, and facilitates the spread of virus among T cells. However, whether HIV cell-to-cell tra...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.07.079
更新日期：2018-08-21 00:00:00
abstract：:The molecular basis of higher regenerative capacity of cold-blooded animals comparing to warm-blooded ones is poorly understood. Although this difference in regenerative capacities is commonly thought to be a result of restructuring of the same regulatory gene network, we hypothesized that it may be due to loss of som...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.09.038
更新日期：2019-10-22 00:00:00
abstract：:Autophagy is an essential cellular survival mechanism that is required for adaptive lymphocyte development; however, its role in innate lymphoid cell (ILC) development remains unknown. Furthermore, the conditions that promote lymphocyte autophagy during homeostasis are poorly understood. Here, we demonstrate that Atg5...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.04.082
更新日期：2016-05-31 00:00:00
abstract：:In fission yeast, the transcription factor Pap1 undergoes H2O2-dependent oxidation that promotes its nuclear accumulation and the activation of an antioxidant gene program. However, the mechanisms that regulate the sensitivity and selectivity of Pap1 activation by peroxides are not fully understood. Here, we demonstra...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2013.11.027
更新日期：2013-12-12 00:00:00
abstract：:Cellular differentiation is associated with dynamic chromatin remodeling in establishing a cell-type-specific epigenomic landscape. Here, we find that mouse testis-specific and replication-dependent histone H3 variant H3t is essential for very early stages of spermatogenesis. H3t gene deficiency leads to azoospermia b...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.12.065
更新日期：2017-01-17 00:00:00
abstract：:Neuropathic pain is a chronic debilitating disease that results from nerve damage, persists long after the injury has subsided, and is characterized by spontaneous pain and mechanical hypersensitivity. Although loss of inhibitory tone in the dorsal horn of the spinal cord is a major contributor to neuropathic pain, th...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.09.080
更新日期：2015-11-10 00:00:00
abstract：:Neuregulin-1 (NRG1) gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions in vivo...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.07.026
更新日期：2014-08-21 00:00:00
abstract：:Insulin-stimulated hepatic glycogen synthesis is central to glucose homeostasis. Here, we show that PPP1R3G, a regulatory subunit of protein phosphatase 1 (PP1), is directly phosphorylated by AKT. PPP1R3G phosphorylation fluctuates with fasting-refeeding cycle and is required for insulin-stimulated dephosphorylation, ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.08.066
更新日期：2019-09-24 00:00:00
abstract：:The subgranular zone (SGZ) of the adult hippocampus contains a pool of quiescent neural progenitor cells (QNPs) that are capable of entering the cell cycle and producing newborn neurons. The mechanisms that control the timing and extent of adult neurogenesis are not well understood. Here, we show that QNPs of the adul...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2013.10.037
更新日期：2013-11-27 00:00:00
abstract：:Evolutionary expansion of the human neocortex is partially attributed to a relative abundance of neural stem cells in the fetal brain called outer radial glia (oRG). oRG cells display a characteristic division mode, mitotic somal translocation (MST), in which the soma rapidly translocates toward the cortical plate imm...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.06.058
更新日期：2014-08-07 00:00:00
abstract：:MicroRNAs (miRNAs) regulate diverse biological processes by repressing mRNAs, but their modest effects on direct targets, together with their participation in larger regulatory networks, make it challenging to delineate miRNA-mediated effects. Here, we describe an approach to characterizing miRNA-regulatory networks b...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.12.031
更新日期：2016-01-12 00:00:00
abstract：:53BP1 plays multiple roles in mammalian DNA damage repair, mediating pathway choice and facilitating DNA double-strand break repair in heterochromatin. Although it possesses a C-terminal BRCT2 domain, commonly involved in phospho-peptide binding in other proteins, initial recruitment of 53BP1 to sites of DNA damage de...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.10.074
更新日期：2015-12-15 00:00:00
abstract：:The quest to extend healthspan via pharmacological means is becoming increasingly urgent, both from a health and economic perspective. Here we show that lithium, a drug approved for human use, promotes longevity and healthspan. We demonstrate that lithium extends lifespan in female and male Drosophila, when administer...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.03.041
更新日期：2016-04-19 00:00:00
abstract：:Long-term information storage in the brain requires continual modification of the neuronal transcriptome. Synaptic inputs located hundreds of micrometers from the nucleus can regulate gene transcription, requiring high-fidelity, long-range signaling from synapses in dendrites to the nucleus in the cell soma. Here, we ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.03.005
更新日期：2019-03-26 00:00:00
abstract：:Reactive astrogliosis is an essential and ubiquitous response to CNS injury, but in some cases, aberrant activation of astrocytes and their release of inhibitory signaling molecules can impair endogenous neural repair processes. Our lab previously identified a secreted intercellular signaling molecule, called endothel...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.11.002
更新日期：2015-12-15 00:00:00
abstract：:Redox-mediated posttranslational modifications represent a molecular switch that controls major mechanisms of cell function. Nitric oxide (NO) can mediate redox reactions via S-nitrosylation, representing transfer of an NO group to a critical protein thiol. NO is known to modulate neurogenesis and neuronal survival in...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.06.005
更新日期：2014-07-10 00:00:00
abstract：:Transcription-factor-induced reprogramming of somatic cells to pluripotency is a very inefficient process, probably due to the existence of important epigenetic barriers that are imposed during differentiation and that contribute to preserving cell identity. In an effort to decipher the molecular nature of these barri...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2013.02.029
更新日期：2013-04-25 00:00:00
