Thrombospondin-1 prevents amyloid beta–mediated synaptic pathology in Alzheimer's disease

Son, Sungmin; Nam, Dong Woo; Moon, Yong; Kim, Kyung Ho; Byun, Ji Won; Ryu, Hoon; Mook‐Jung, Inhee

doi:10.1016/j.neurobiolaging.2015.09.005

Cited by 41 publications

(43 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…THBS1 could decrease neuronal excitability via reducing AMPA receptors (AMPARs) and increasing glycine receptors (GlyRs) in synapses [ 36 ]. Some researches suggested that THBS1 helped the recovery of normal synaptic activity after injury responses [ 37 ] and even was a potential therapeutic target in the pathogenesis of Alzheimer's disease [ 38 ]. Many studies [ 39 , 40 ] indicated that LncRNAs played key role in the neuronal degeneration disease which was involved in the progressive loss of structure or function of neurons, including death of neurons.…”

Section: Discussionmentioning

confidence: 99%

Aberrant LncRNA Expression Profile in a Contusion Spinal Cord Injury Mouse Model

Ding

Song

Wang

2016

BioMed Research International

View full text Add to dashboard Cite

Long noncoding RNAs (LncRNAs) play a crucial role in cell growth, development, and various diseases related to the central nervous system. However, LncRNA differential expression profiles in spinal cord injury are yet to be reported. In this study, we profiled the expression pattern of LncRNAs using a microarray method in a contusion spinal cord injury (SCI) mouse model. Compared with a spinal cord without injury, few changes in LncRNA expression levels were noted 1 day after injury. The differential changes in LncRNA expression peaked 1 week after SCI and subsequently declined until 3 weeks after injury. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the reliability of the microarray, demonstrating that the results were reliable. Gene ontology (GO) analysis indicated that differentially expressed mRNAs were involved in transport, cell adhesion, ion transport, and metabolic processes, among others. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the neuroactive ligand-receptor interaction, the PI3K-Akt signaling pathway, and focal adhesions were potentially implicated in SCI pathology. We constructed a dynamic LncRNA-mRNA network containing 264 LncRNAs and 949 mRNAs to elucidate the interactions between the LncRNAs and mRNAs. Overall, the results from this study indicate for the first time that LncRNAs are differentially expressed in a contusion SCI mouse model.

show abstract

Section: Discussionmentioning

confidence: 99%

Aberrant LncRNA Expression Profile in a Contusion Spinal Cord Injury Mouse Model

Ding

Song

Wang

2016

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…TSP1 plays a protective role in non-ischemic neurological pathology such as Alzheimer’s disease (AD), fragile X syndrome, and Down syndrome, both are associated with serious mental impairments and reduced synaptic plasticity. Decreased expression of TSP1 was shown in a subset of cortical pyramidal neurons and astrocytes that are prone to AD [ 178 , 179 ]. TSP1 was shown to protect neurons against β-amyloid-induced synaptic degeneration [ 179 ].…”

Section: Tsps In Other Pathologiesmentioning

confidence: 99%

“…Decreased expression of TSP1 was shown in a subset of cortical pyramidal neurons and astrocytes that are prone to AD [ 178 , 179 ]. TSP1 was shown to protect neurons against β-amyloid-induced synaptic degeneration [ 179 ]. On the other hand, β-amyloid inhibits release of TSP1 by astrocytes that in turn attenuates expression of synaptic proteins such as synaptophysin and PSD95 followed by aberrations in the morphology of dendritic spines and reduction of synaptic plasticity [ 180 ].…”

Section: Tsps In Other Pathologiesmentioning

confidence: 99%

Thrombospondins: A Role in Cardiovascular Disease

Chistiakov

Melnichenko

Myasoedova

et al. 2017

IJMS

View full text Add to dashboard Cite

Thrombospondins (TSPs) represent extracellular matrix (ECM) proteins belonging to the TSP family that comprises five members. All TSPs have a complex multidomain structure that permits the interaction with various partners including other ECM proteins, cytokines, receptors, growth factors, etc. Among TSPs, TSP1, TSP2, and TSP4 are the most studied and functionally tested. TSP1 possesses anti-angiogenic activity and is able to activate transforming growth factor (TGF)-β, a potent profibrotic and anti-inflammatory factor. Both TSP2 and TSP4 are implicated in the control of ECM composition in hypertrophic hearts. TSP1, TSP2, and TSP4 also influence cardiac remodeling by affecting collagen production, activity of matrix metalloproteinases and TGF-β signaling, myofibroblast differentiation, cardiomyocyte apoptosis, and stretch-mediated enhancement of myocardial contraction. The development and evaluation of TSP-deficient animal models provided an option to assess the contribution of TSPs to cardiovascular pathology such as (myocardial infarction) MI, cardiac hypertrophy, heart failure, atherosclerosis, and aortic valve stenosis. Targeting of TSPs has a significant therapeutic value for treatment of cardiovascular disease. The activation of cardiac TSP signaling in stress and pressure overload may be therefore beneficial.

show abstract

“…Aβ could alter peptidergic secretion influencing vesicular biogenesis, trafficking and exocytosis. It has been shown that soluble Aβ forms induce key changes which could compromise the integrity of the secretory pathway at early stages, such as endoplasmic reticulum stress, Golgi fragmentation and autophagy (Alberdi et al, 2013; Joshi et al, 2014; Son et al, 2015). Moreover, Aβ can also impair transport, docking and discharge of secretory vesicles.…”

Section: Discussionmentioning

confidence: 99%

Amyloid-β Impairs Vesicular Secretion in Neuronal and Astrocyte Peptidergic Transmission

Plá

Barranco

Pozas

et al. 2017

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Regulated secretion of neuropeptides and neurotrophic factors critically modulates function and plasticity of synapses and circuitries. It is believed that rising amyloid-β (Aβ) concentrations, synaptic dysfunction and network disorganization underlie early phases of Alzheimer’s disease (AD). Here, we analyze the impact of soluble Aβ1–42 assemblies on peptidergic secretion in cortical neurons and astrocytes. We show that neurons and astrocytes differentially produce and release carboxypeptidase E (CPE) and secretogranin III (SgIII), two dense-core vesicle (DCV) markers belonging to the regulated secretory pathway. Importantly, Aβ1–42, but not scrambled Aβ1–42, dramatically impairs basal and Ca2+-regulated secretions of endogenously produced CPE and SgIII in cultured neurons and astrocytes. Additionally, KCl-evoked secretion of the DCV cargo brain-derived neurotrophic factor (BDNF) is lowered by Aβ1–42 administration, whereas glutamate release from synaptic vesicle (SVs) remains unchanged. In agreement with cell culture results, Aβ1–42 effects on CPE and SgIII secretion are faithfully recapitulated in acute adult brain slices. These results demonstrate that neuronal and astrocyte secretion of DCV cargos is impaired by Aβ in vitro and in situ. Furthermore, Aβ-induced dysregulated peptidergic transmission could have an important role in the pathogenesis of AD and DCV cargos are possible candidates as cerebrospinal fluid (CSF) biomarkers.

show abstract

Thrombospondin-1 prevents amyloid beta–mediated synaptic pathology in Alzheimer's disease

Cited by 41 publications

References 54 publications

Aberrant LncRNA Expression Profile in a Contusion Spinal Cord Injury Mouse Model

Aberrant LncRNA Expression Profile in a Contusion Spinal Cord Injury Mouse Model

Thrombospondins: A Role in Cardiovascular Disease

Amyloid-β Impairs Vesicular Secretion in Neuronal and Astrocyte Peptidergic Transmission

Contact Info

Product

Resources

About