Abstract:
:Alzheimer disease (AD) is usually accompanied by two prominent pathological features, cerebral accumulation of amyloid-β (Aβ) plaques and presence of MAPT/tau neurofibrillary tangles. Dysregulated clearance of Aβ largely contributes to its accumulation and plaque formation in the brain. Macroautophagy/autophagy is a lysosomal degradative process, which plays an important role in the clearance of Aβ. Failure of autophagic clearance of Aβ is currently acknowledged as a contributing factor to increased accumulation of Aβ in AD brains. In this study, we have identified crocetin, a pharmacologically active constituent from the flower stigmas of Crocus sativus, as a potential inducer of autophagy in AD. In the cellular model, crocetin induced autophagy in N9 microglial and primary neuron cells through STK11/LKB1 (serine/threonine kinase 11)-mediated AMP-activated protein kinase (AMPK) pathway activation. Autophagy induction by crocetin significantly increased Aβ clearance in N9 cells. Moreover, crocetin crossed the blood-brain barrier and induced autophagy in the brains' hippocampi of wild-type male C57BL/6 mice. Further studies in transgenic male 5XFAD mice, as a model of AD, revealed that one-month treatment with crocetin significantly reduced Aβ levels and neuroinflammation in the mice brains and improved memory function by inducing autophagy that was mediated by AMPK pathway activation. Our findings support further development of crocetin as a pharmacological inducer of autophagy to prevent, slow down progression, and/or treat AD.
journal_name
Autophagyjournal_title
Autophagyauthors
Wani A,Al Rihani SB,Sharma A,Weadick B,Govindarajan R,Khan SU,Sharma PR,Dogra A,Nandi U,Reddy CN,Bharate SS,Singh G,Bharate SB,Vishwakarma RA,Kaddoumi A,Kumar Adoi
10.1080/15548627.2021.1872187subject
Has Abstractpub_date
2021-01-19 00:00:00pages
1-20eissn
1554-8627issn
1554-8635pub_type
杂志文章相关文献
Autophagy文献大全abstract::Salinomycin is perhaps the first promising compound that was discovered through high throughput screening in cancer stem cells. This novel agent can selectively eliminate breast and other cancer stem cells, though the mechanism of action remains unclear. In this study, we found that salinomycin induced autophagy in hu...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.24632
更新日期:2013-07-01 00:00:00
abstract::The N-terminal amino acid of a protein is an essential determinant of ubiquitination and subsequent proteasomal degradation in the N-end rule pathway. Using para-chloroamphetamine (PCA), a specific inhibitor of the arginylation branch of the pathway (Arg/N-end rule pathway), we identified that blocking the Arg/N-end r...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2016.1222991
更新日期:2016-11-01 00:00:00
abstract::The 4th International Symposium on Autophagy was held in Mishima, a small town between Tokyo and Kyoto, October 1-5, 2006 (http://isa4th.umin.jp/). The meeting was organized by the group of Eiki Kominami. Approximately 150 participants took part in this well-organized meeting in the spacious and comfortable Toray Conf...
journal_title:Autophagy
pub_type:
doi:10.4161/auto.3654
更新日期:2007-03-01 00:00:00
abstract::Ferroptosis is a form of regulated cell death caused by iron accumulation and oxidative injury. BECN1 is a key regulator of macroautophagy/autophagy, a catabolic process of degradation induced by starvation or other stressors. Our recent findings reveal a novel alternative mechanism by which BECN1 can promote ferropto...
journal_title:Autophagy
pub_type: 评论,杂志文章
doi:10.1080/15548627.2018.1513758
更新日期:2018-01-01 00:00:00
abstract::The Atg1/ULK1 complex plays a central role in starvation-induced autophagy, integrating signals from upstream sensors such as MTOR and AMPK and transducing them to the downstream autophagy pathway. Much progress has been made in the last few years in understanding the mechanisms by which the complex is regulated throu...
journal_title:Autophagy
pub_type: 杂志文章,评审
doi:10.4161/auto.23323
更新日期:2013-02-01 00:00:00
abstract::It has not been elucidated whether or not autophagy is induced by rhabdoviral G glycoproteins (G) in vertebrate organisms for which rhabdovirus infection is lethal. Our work provides the first evidence that both mammalian (vesicular stomatitis virus, VSV) and fish (viral hemorrhagic septicemia virus, VHSV, and spring ...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.29557
更新日期:2014-09-01 00:00:00
abstract::The aging process drives the progressive deterioration of an organism and is thus subject to a complex interplay of regulatory and executing mechanisms. Our understanding of this process eventually aims at the delay and/or prevention of age-related pathologies, among them the age-dependent decrease in cognitive perfor...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.26918
更新日期:2014-01-01 00:00:00
abstract::Premenopausal women have better survival than men after intracerebral hemorrhage, which is associated with iron overproduction and autophagy induction. To examine the participation of neuronal autophagy and estrogen receptor α (ERα) in the E 2-mediated protection, PC12 neurons treated with Atg7 (autophagy-related prot...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.21289
更新日期:2012-10-01 00:00:00
abstract::Autophagy has recently been implicated in the host defense against the intracellular protozoan pathogen, Toxoplasma gondii, a major opportunistic pathogen of the central nervous system in immunosuppressed individuals. In both IFN gamma-activated macrophages and astrocytes, the p47 GTPases traffic to the T. gondii para...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.5.2.7637
更新日期:2009-02-01 00:00:00
abstract::Microglia are innate immune cells in the central nervous system (CNS), that supplies neurons with key factors for executing autophagosomal/lysosomal functions. Macroautophagy/autophagy is a cellular catabolic process that maintains cell balance in response to stress-related stimulation. Abnormal autophagy occurs with ...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2018.1522467
更新日期:2019-03-01 00:00:00
abstract::Oxidative stress (OS) stimulates autophagy in different cellular systems, but it remains controversial if this rule can be generalized. We have analyzed the effect of chronic OS induced by the parkinsonian toxin paraquat (PQ) on autophagy in astrocytoma cells and primary astrocytes, which represent the first cellular ...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2015.1058683
更新日期:2015-01-01 00:00:00
abstract::Autophagy is a process of bulk protein degradation and organelle turnover, and is a current therapeutic target in several diseases. The present study aimed to clarify the significance of myocardial autophagy of patients with dilated cardiomyopathy (DCM). Left ventricular endomyocardial biopsy was performed in 250 cons...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2016.1145326
更新日期:2016-01-01 00:00:00
abstract::How lysosome and MTORC1 signaling interact remains elusive in terminally differentiated cells. A G4C2 repeat expansion in C9orf72 is the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9ALS-FTD). We previously identified a C9orf72-SMCR8-containing complex. Here we ...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2019.1703353
更新日期:2020-09-01 00:00:00
abstract::Acute promyelocytic leukemia (APL) is characterized by a chromosomal t(15;17) translocation that fuses the gene encoding the promyelocytic leukemia protein (PML) to that encoding retinoic acid receptor alpha (RARA). The product of this genetic aberration, the PML/RARA fusion protein, is highly oncogenic and supports m...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.6.7.13066
更新日期:2010-10-01 00:00:00
abstract::Regulation of intestinal epithelial turnover is a key component of villus maintenance in the intestine. The balance of cell turnover can be perturbed by various extrinsic factors including the cytokine TNF, a cell signaling protein that mediates both proliferative and cytotoxic outcomes. Under conditions of infection ...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2019.1596495
更新日期:2019-11-01 00:00:00
abstract::Understanding of the mechanism for myeloid differentiation provides important insights into the hematopoietic developmental processes. By using an ESC-derived myeloid progenitor cell model, we found that CSF2/GM-CSF triggered macrophage differentiation and activation of the MTOR signaling pathway. Activation or inhibi...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2019.1578040
更新日期:2019-07-01 00:00:00
abstract::To examine the functional significance and detailed morphological characteristics of starvation-induced autophagy in the adult heart, we starved green fluorescent protein (GFP)-microtubule-associated protein 1 light chain 3 (LC3) transgenic mice for up to 3 days. Electron microscopy revealed that, after as little as 1...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.5.7.9297
更新日期:2009-10-01 00:00:00
abstract::Macroautophagy/autophagy is emerging as an important process in adult muscle stem cells functions: it regulates metabolic reprogramming during activation from a quiescent state, maintains stemness and prevents senescence. We now show that autophagy is specifically required for neonatal myogenesis and muscle developmen...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2018.1507439
更新日期:2019-01-01 00:00:00
abstract::The conserved target of rapamycin (TOR) kinase is a central regulator of cell growth in response to nutrient availability. TOR forms 2 structurally and functionally distinct complexes, TORC1 and TORC2, and negatively regulates autophagy via TORC1. Here we demonstrate TOR also operates independently through the TORC2 s...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.36262
更新日期:2014-01-01 00:00:00
abstract::SPHK1 (sphingosine kinase 1), a regulator of sphingolipid metabolites, plays a causal role in the development of hepatocellular carcinoma (HCC) through augmenting HCC invasion and metastasis. However, the mechanism by which SPHK1 signaling promotes invasion and metastasis in HCC remains to be clarified. Here, we repor...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2017.1291479
更新日期:2017-05-04 00:00:00
abstract::Delivery of cellular contents to yeast vacuoles/mammalian lysosomes via autophagy ensures long-term cell survival and extends life span. When cultured yeast cells are grown for a prolonged period of time to enter stationary phase, a nondividing state mimicking quiescence, vacuolar membrane proteins partition into eith...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.36137
更新日期:2014-01-01 00:00:00
abstract::Macroautophagy/autophagy involves the formation of an autophagosome, a double-membrane vesicle that delivers sequestered cytoplasmic cargo to lysosomes for degradation and recycling. Closely related, endocytosis mediates the sorting and transport of cargo throughout the cell, and both processes are important for cellu...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2017.1356976
更新日期:2017-10-03 00:00:00
abstract::Adaptive immunity, which plays an important role in the development of atherosclerosis, is mediated by major histocompatibility complex (MHC)-dependent antigen presentation. In atherosclerotic lesions, macrophages constitute an important class of antigen-presenting cells that activate adaptive immune responses to oxid...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2015.1037061
更新日期:2015-01-01 00:00:00
abstract::Phagocytosis plays a central role in immunity and tissue homeostasis. After internalization of cargo into single-membrane phagosomes, these compartments undergo a maturation sequences that terminates in lysosome fusion and cargo degradation. Components of the autophagy pathway have recently been linked to phagosome ma...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2016.1191724
更新日期:2016-09-01 00:00:00
abstract::Macroautophagy/autophagy is an intracellular stress survival and recycling system whereas phagocytosis internalizes material from the extracellular milieu; yet, both pathways utilize lysosomes for cargo degradation. Whereas autophagy occurs in all cells, phagocytosis is performed by cell types such as macrophages and ...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2017.1380124
更新日期:2017-01-01 00:00:00
abstract::A hallmark of macroautophagy is the formation of autophagosomes, double-membrane vesicles that enwrap cellular components destined for lysosomal degradation. We examined autophagosomal protein dynamics under various inducing stimuli using a comprehensive mass spectrometry-based proteomics approach in combination with ...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.20286
更新日期:2012-06-01 00:00:00
abstract::ULK1 and ATG13 assemble with RB1CC1/FIP200 and ATG101 to form a macroautophagy (hereafter autophagy) induction (ULK1) complex in higher eukaryotes. The yeast counterpart, the Atg1 complex, is comprised of Atg1 and Atg13 (ULK1 and ATG13 homologs), Atg17 (a proposed functional homolog of RB1CC1), and either the Atg101 s...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2015.1087635
更新日期:2015-11-02 00:00:00
abstract::Overcoming metabolic stress is a critical step in tumorigenesis. Acetyl coenzyme A (acetyl-CoA) converted from glucose or acetate is a substrate used for histone acetylation to regulate gene expression. However, how acetyl-CoA is produced under nutritional stress conditions is unclear. Herein we report that nutritiona...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2017.1349581
更新日期:2017-10-03 00:00:00
abstract::Mitochondria are the primary site of energy production in animal cells. In mitochondria, the flow of electrons through the electron transport chain creates a potential difference across the inner membrane, which is utilized for ATP production. However, due to inherent inefficiencies in electron transport, reactive oxy...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.6.3.11245
更新日期:2010-04-01 00:00:00
abstract::Under stress conditions cells activate different response pathways which result in cell survival or apoptosis depending on: (1) the nature of the insults, (2) the type, if acute or chronic stress, and (3) how long the stress persists. Generally, autophagy is induced early to sustain cell survival and inhibit cell deat...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.20671
更新日期:2012-08-01 00:00:00