Abstract:
:Cellular clearance mechanisms including the autophagy-lysosome pathway are impaired in amyotrophic lateral sclerosis (ALS). One of the most important proteins involved in the regulation of autophagy is the lysosomal Ca2+ channel Mucolipin TRP channel 1 (TRPML1). Therefore, we investigated the role of TRPML1 in a neuronal model of ALS/Parkinson-dementia complex reproduced by the exposure of motor neurons to the cyanobacterial neurotoxin beta-methylamino-L-alanine (L-BMAA). Under these conditions, L-BMAA induces a dysfunction of the endoplasmic reticulum (ER) leading to ER stress and cell death. Therefore we hypothesized a dysfunctional coupling between lysosomes and ER in L-BMAA-treated motor neurons. Here, we showed that in motor neuronal cells TRPML1 as well as the lysosomal protein LAMP1 co-localized with ER. In addition, TRPML1 co-immunoprecipitated with the ER Ca2+ sensor STIM1. Functionally, the TRPML1 agonist ML-SA1 induced lysosomal Ca2+ release in a dose-dependent way in motor neuronal cells. The SERCA inhibitor thapsigargin increased the fluorescent signal associated with lysosomal Ca2+ efflux in the cells transfected with the genetically encoded Ca2+ indicator GCaMP3-ML1, thus suggesting an interplay between the two organelles. Moreover, chronic exposure to L-BMAA reduced TRPML1 protein expression and produced an impairment of both lysosomal and ER Ca2+ homeostasis in primary motor neurons. Interestingly, the preincubation of ML-SA1, by an early activation of AMPK and beclin 1, rescued motor neurons from L-BMAA-induced cell death and reduced the expression of the ER stress marker GRP78. Finally, ML-SA1 reduced the accumulation of the autophagy-related proteins p62/SQSTM1 and LC3-II in L-BMAA-treated motor neurons. Collectively, we propose that the pharmacological stimulation of TRPML1 can rescue motor neurons from L-BMAA-induced toxicity by boosting autophagy and reducing ER stress.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Tedeschi V,Petrozziello T,Sisalli MJ,Boscia F,Canzoniero LMT,Secondo Adoi
10.1038/s41598-019-46708-5subject
Has Abstractpub_date
2019-07-24 00:00:00pages
10743issue
1issn
2045-2322pii
10.1038/s41598-019-46708-5journal_volume
9pub_type
杂志文章abstract::Liver chips have been developed to recapitulate in vivo physiological conditions to enhance hepatocyte functions for assessing acute responses to drugs. To develop liver chips that can assess repeated dosing chronic hepatotoxicity, we need to ensure that hepatocyte functions be maintained at constant values over two w...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-13848-5
更新日期:2017-11-06 00:00:00
abstract::The sensitivity of localized surface plasmon resonance (LSPR) of metal nanostructures to adsorbates lends itself to a powerful class of label-free biosensors. Optical properties of plasmonic nanostructures are dependent on the geometrical features and the local dielectric environment. The exponential decay of the sens...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep16206
更新日期:2015-11-10 00:00:00
abstract::Empathetic verbal feedback from others has been shown to alleviate the intensity of experimental pain. To investigate the brain changes associated with this effect, we conducted 3T-fMRI measurements in 30 healthy subjects who received painful thermal stimuli on their left hand while overhearing empathetic, neutral or ...
journal_title:Scientific reports
pub_type: 临床试验,杂志文章
doi:10.1038/s41598-019-44879-9
更新日期:2019-06-10 00:00:00
abstract::Topical anesthetics are widely applied in order to relieve the discomfort and anxiety caused by needle insertion and other painful superficial interventions at the oral cavity. So far, there are no commercially available effective topical anesthetic formulations for that purpose, and the most of developments are relat...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-68247-0
更新日期:2020-07-09 00:00:00
abstract::We report, for the first time, the generation of high-order harmonics in a spectral range between 200 eV and 1 keV with an unusual spectral property: only every 4(th) (4i + 1, i∈ℵ) harmonic line appears, whereas the usual high-harmonic spectra consist of every odd (2i + 1) harmonic. We attribute this unique property t...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep04234
更新日期:2014-02-28 00:00:00
abstract::Pancreatic cancer (PC), as the leading cause of cancer death worldwide, is one of the deadliest tumors with a very low 5-year survival rate. Therefore, it is urgent to seek new biomarkers of PC for more accurate and reliable treatments. To identify the differentially expressed miRNAs (DEM) in PC tissues, we performed ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-11248-3
更新日期:2017-09-13 00:00:00
abstract::Dopamine (DA) plays significant roles in regulation of social behavior. In social groups of humans and other animals, social hierarchy exists, which is determined by several behavioral characteristics such as aggression and impulsivity as well as social affiliations. In this study, we investigated the effects of pharm...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep43348
更新日期:2017-02-24 00:00:00
abstract::Previous studies of protein fold space suggest that fold coverage is plateauing. However, sequence sampling has been -and remains to a large extent- heavily biased, focusing on culturable phyla. Sustained technological developments have fuelled the advent of metagenomics and single-cell sequencing, which might correct...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep14717
更新日期:2015-10-05 00:00:00
abstract::Majority of novel X-ray crystal structures of proteins are currently solved using the anomalous diffraction signal provided by selenium after incorporation of selenomethionine instead of natural methionine by genetic engineering methods. However, selenium can be inserted into protein crystals in the form of selenourea...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep37123
更新日期:2016-11-14 00:00:00
abstract::Despite strengthened antimicrobial therapy, biofilm infections of Acinetobacter baumannii are associated with poor prognosis and limited therapeutic options. Assessing antibiotics on planktonic bacteria can result in failure against biofilm infections. Currently, antibiotics to treat biofilm infections are administere...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-42353-0
更新日期:2019-04-19 00:00:00
abstract::Transition metal oxides (TMOs) exhibit many emergent phenomena ranging from high-temperature superconductivity and giant magnetoresistance to magnetism and ferroelectricity. In addition, when TMOs are interfaced with each other, new functionalities can arise, which are absent in individual components. Here, we report ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep05368
更新日期:2014-06-20 00:00:00
abstract::A patient's pain during mandibular third molar extraction often creates problems for a dental surgeon and can also cause immense patient discomfort, such as decreased quality of life, serious complications, or even danger to the patients' lives. Effective pain management is therefore of great importance. Conventional ...
journal_title:Scientific reports
pub_type: 杂志文章,meta分析,评审
doi:10.1038/srep40987
更新日期:2017-01-20 00:00:00
abstract::Methylated non-CpGs (mCpH; H means A, C, and T) have emerged as key epigenetic marks in mammalian embryonic stem cells (ESCs) and neurons, regulating cell type-specific functions. In these two cell types, mCpHs show distinct motifs and correlations to transcription that could be a key in understanding the cell type-sp...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-11800-1
更新日期:2017-09-12 00:00:00
abstract::We report a new family with autosomal dominant inheritance of a late onset rapidly progressive leukodystrophy in which exome sequencing has revealed a novel mutation p.R782G in the Colony-Stimulating Factor 1 Receptor gene (CSF1R). Neuropathology of two affected family members showed cerebral white matter degeneration...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep10042
更新日期:2015-05-15 00:00:00
abstract::Burkholderia terrae BS001 has previously been found to be able to disperse along with growing fungal hyphae in soil, with the type-3 secretion system having a supportive role in this movement. In this study, we focus on the role of two motility- and adherence-associated appendages, i.e. type-4 pili (T4P) and flagella....
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-02959-8
更新日期:2017-06-07 00:00:00
abstract::N(1)-methyladenosine (m(1)A) is a prominent RNA modification involved in many biological processes. Accurate identification of m(1)A site is invaluable for better understanding the biological functions of m(1)A. However, limitations in experimental methods preclude the progress towards the identification of m(1)A site...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep31080
更新日期:2016-08-11 00:00:00
abstract::Gallic acid is a trihydroxybenzoic acid found in tea leaves and some plants. Here, we report the effect of gallic acid on cardiac dysfunction and fibrosis in a mouse model of pressure overload-induced heart failure and in primary rat cardiac fibroblasts, and compare the effects of gallic acid with those of drugs used ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-27599-4
更新日期:2018-06-18 00:00:00
abstract::CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) plays an important role in tumor progression and a number of studies have suggested that it is an indicator of tumor prognosis. This current meta-analysis systematically reevaluated the predictive potential of CD147/EMMPRIN in various cancers. We searched ...
journal_title:Scientific reports
pub_type: 杂志文章,评审
doi:10.1038/srep32804
更新日期:2016-09-09 00:00:00
abstract::Individuals in the state of psychological suboptimal health keep increasing, only scales and questionnaires were used to diagnose in clinic under current conditions, and symptoms of high reliability and accuracy are destitute. Therefore, the noninvasive and precise laboratory diagnostic methods are needed. This study ...
journal_title:Scientific reports
pub_type: 临床试验,杂志文章
doi:10.1038/srep33820
更新日期:2016-09-21 00:00:00
abstract::Herein, we demonstrate a simple yet novel luminescence assay for visual chiral discrimination of cysteine. Thioglycolic acid (TGA)-capped cadmium-telluride (CdTe) quantum dots (QDs) exposing green emission were directly synthesized in aqueous solution. The interaction between cysteine molecules and CdTe QDs induced th...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-00983-2
更新日期:2017-04-18 00:00:00
abstract::A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-017-14857-0
更新日期:2017-11-16 00:00:00
abstract::Microvascular endothelial cell heterogeneity and its relationship to hemodynamics remains poorly understood due to a lack of sufficient methods to examine these parameters in vivo at high resolution throughout an angiogenic network. The availability of surrogate markers for functional vascular proteins, such as green ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-08982-z
更新日期:2017-08-22 00:00:00
abstract::Males of hymenopteran insects, which include ants, bees and wasps, develop as haploids from unfertilized eggs. In order to accommodate their lack of homologous chromosome pairs, some hymenopterans such as the honeybee have been shown to produce haploid sperm through an abortive meiosis. We employed microscopic approac...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-48332-9
更新日期:2019-08-21 00:00:00
abstract::Patients with stress-induced exhaustion disorder (SED) demonstrate cognitive dysfunction similar to patients with minor traumatic brain injury (TBI). We have previously detected elevated concentrations of astrocyte-derived extracellular vesicles (EVs) in patients with TBI. As such, we hypothesized that astrocyte-deriv...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-021-81453-8
更新日期:2021-01-21 00:00:00
abstract::In this article, we report the first observation of nanosecond laser induced transient dual absorption bands, one in the bandgap (TA₁) and another in the sub-bandgap (TA₂) regions of a-Ge₅As₃₀Se₆₅ thin films. Strikingly, these bands are thermally tunable and exhibit a unique contrasting characteristic: the magnitude o...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep06573
更新日期:2014-10-10 00:00:00
abstract::Large-strain elastic superhydrophobicity is highly desirable for its enhanced use performance and functional reliability in mechanically dynamic environments, but remains challenging to develop. Here we have, for the first time, proven that an elastic fibrous membrane after surface hydrophobization can maintain superh...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep15863
更新日期:2015-10-29 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-020-67913-7
更新日期:2020-06-30 00:00:00
abstract::Alterations in the gut microbiome have been reported in liver cirrhosis, and probiotic interventions are considered a potential treatment strategy. This study aimed to evaluate the effects and mechanisms of Lactobacillus salivarius LI01, Pediococcus pentosaceus LI05, Lactobacillus rhamnosus GG, Clostridium butyricum M...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-07091-1
更新日期:2017-07-31 00:00:00
abstract::Protein phosphorylation is an important type of post-translational modification that is involved in a variety of biological activities. Most phosphorylation events occur on serine, threonine and tyrosine residues in eukaryotes. In recent years, many phosphorylation sites have been identified as a result of advances in...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep24735
更新日期:2016-04-19 00:00:00
abstract::Severe sepsis and septic shock are life-threatening conditions, with Gram-negative organisms responsible for most sepsis mortality. Systemic administration of compounds that block the action of lipopolysaccharide (LPS), a constituent of the Gram-negative outer cell membrane, is hampered by their hydrophobicity and cat...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep29739
更新日期:2016-07-14 00:00:00