共查询到20条相似文献,搜索用时 15 毫秒
1.
The main component of senile plaques found in AD brain is amyloid β-peptide (Aβ), and the neurotoxicity and aggregation of
Aβ are associated with the formation of β-sheet structure. Experimentally, beta sheet breaker (BSB) peptide fragment Leu-Pro-Phe-Phe-Asp
(LPFFD) can combine with Aβ, which can inhibit the aggregation of Aβ. In order to explore why LPFFD can inhibit the formation
of β-sheet conformation of Aβ at atomic level, first, molecular docking is performed to obtain the binding sites of LPFFD
on the Aβ(1–42) (LPFFD/Aβ(1–42)), which is taken as the initial conformation for MD simulations. Then, MD simulations on LPFFD/Aβ(1–42)
in water are carried out. The results demonstrate that LPFFD can inhibit the conformational transition from α-helix to β-sheet
structure for the C-terminus of Aβ(1–42), which may be attributed to the hydrophobicity decreasing of C-terminus residues
of Aβ(1–42) and formation probability decreasing of the salt bridge Asp23-Lys28 in the presence of LPFFD. 相似文献
2.
Yuan C Yi L Yang Z Deng Q Huang Y Li H Gao Z 《Journal of biological inorganic chemistry》2012,17(2):197-207
Amyloid beta (Aβ) peptide accumulation has been demonstrated to play a central role in Alzheimer’s disease (AD). Substantial
evidence indicates that protein nitrotyrosination contributes to Aβ-dependent neurotoxicity; however, the molecular mechanism
is unknown. Recent research has shown that Aβ complexes with heme to form Aβ–heme, and increases the pseudo-peroxidase activity
of heme. We found that Aβ–heme uses H2O2 and NO2
− to cause nitration of enolase and synaptic proteins more effectively than heme. Thus, the increased peroxidase activity of
Aβ–heme may be the molecular link between excess Aβ and the widespread protein nitration in AD. Interestingly, the site of
enolase nitration that was catalyzed by Aβ–heme is different from that induced by heme. Moreover, the secondary structural
perturbations of Aβ–heme-treated and heme-treated enolase are also different. These observations suggest that Aβ–heme targets
specific amino acid sequences in enolase. Furthermore, our data show that Aβ–heme peroxidase activity is independent of the
aggregation state of Aβ, suggesting an important role of soluble Aβ in addition to Aβ aggregates and oligomers in AD pathogenesis. 相似文献
3.
Frozza RL Horn AP Hoppe JB Simão F Gerhardt D Comiran RA Salbego CG 《Neurochemical research》2009,34(2):295-303
Accumulation of the neurotoxic amyloid β-peptide (Aβ) in the brain is a hallmark of Alzheimer’s disease (AD). Several synthetic
Aβ peptides have been used to study the mechanisms of toxicity. Here, we sought to establish comparability between two commonly
used Aβ peptides Aβ1-42 and Aβ25-35 on an in vitro model of Aβ toxicity. For this purpose we used organotypic slice cultures
of rat hippocampus and observed that both Aβ peptides caused similar toxic effects regarding to propidium iodide uptake and
caspase-3 activation. In addition, we also did not observe any effect of both peptides on Akt and PTEN phosphorylation; otherwise
the phosphorylation of GSK-3β was increased. Although further studies are necessary for understanding mechanisms underlying
Aβ peptide toxicity, our results provide strong evidence that Aβ1-42 and the Aβ25-35 peptides induce neural injury in a similar
pattern and that Aβ25-35 is a convenient tool for the investigation of neurotoxic mechanisms involved in AD. 相似文献
4.
Hani Atamna 《Journal of bioenergetics and biomembranes》2009,41(5):457-464
Soluble oligomers and/or aggregates of Amyloid-β (Aβ) are viewed by many as the principal cause for neurodegeneration in Alzheimer’s
disease (AD). However, the mechanism by which Aβ and its aggregates cause neurodegeneration is not clear. The toxicity of
Aβ has been attributed to its hydrophobicity. However, many specific mitochondrial cytopathologies e.g., loss of complex IV,
loss of iron homeostasis, or oxidative damage cannot be explained by Aβ’s hydrophobicity. In order to understand the role
of Aβ in these cytopathologies we hypothesized that Aβ impairs specific metabolic pathways. We focused on heme metabolism
because it links iron, mitochondria, and Aβ. We generated experimental evidence showing that Aβ alters heme metabolism in
neuronal cells. Furthermore, we demonstrated that Aβ binds to and depletes intracellular regulatory heme (forming an Aβ-heme
complex), which provides a strong molecular connection between Aβ and heme metabolism. We showed that heme depletion leads
to key cytopathologies identical to those seen in AD including loss of iron homeostasis and loss of mitochondrial complex
IV. Aβ-heme exhibits a peroxidase-like catalytic activity, which catalytically accelerates oxidative damage. Interestingly,
the amino acids sequence of rodent Aβ (roAβ) and human Aβ (huAβ) is identical except for three amino acids within the hydrophilic
region, which is also the heme-binding motif that we identified. We found that huAβ, unlike roAβ, binds heme tightly and forms
a peroxidase. Although, roAβ and huAβ equally form fibrils and aggregates, rodents do not develop AD-like neuropathology.
These findings led us to propose a new mechanism for mitochondrial dysfunction and huAβ’s neurotoxicity. This mechanism prompted
the development of methylene blue (MB), which increased heme synthesis, complex IV, and mitochondrial function. Thus, MB may
delay the onset and progression of AD and serve as a lead to develop novel drugs to treat AD. 相似文献
5.
Giuseppe D. Ciccotosto Kevin J. Barnham Robert A. Cherny Colin L. Masters Ashley I. Bush Cyril C. Curtain Roberto Cappai Deborah Tew 《International journal of peptide research and therapeutics》2003,10(5-6):413-417
Summary The amyloid β-peptide, Aβ is toxic to neurons and this toxicity plays a central role in the progression of Alzheimer's disease.
The mechanism(s) by which Aβ exerts its toxicity has been hotly debated with several theories postulated. Here we discuss
the role of oxidation of the sulfur atom of Met35 in Aβ42 (Met(O)Aβ), a modification that has significant implications for
the mechanism of Aβ toxicity. Both Met(O)Aβ and its native form display toxicity to primary neuronal cells in culture which
can be rescued by catalase, a H2O2 inhibitor and clioquinol a mild copper chelator. However both native Aβ and Met(O)Aβ differ substantially in primary and
secondary structures, solubility, ability to penetrate lipid membranes, and oligomerization profiles. It is clearly evident
that metals play an important role in the oxidation of Aβ to Met(O)Aβ via Fenton chemistry and that regulation of this pathway
has a potential therapeutic application for the regulation of Alzheimer's disease. 相似文献
6.
Feda E. Ali Kevin J. Barnham Colin J. Barrow Frances Separovic 《International journal of peptide research and therapeutics》2003,10(5-6):405-412
Summary Metal-catalyzed oxidation (MCO) can lead to damage of bio-molecules and is implicated in neurodegenerative diseases, such
as Alzheimer's disease (AD). The amino acid residues, tyrosine, histidine and methionine, have been proposed to play important
roles in metal mediated oxidative stress and subsequent reactions of amyloid β peptide (Aβ) a major contributor in the pathogenesis
of AD. The MCO of Aβ residues, particularly histidine, methionine and tyrosine, and reviewed. MCO of Aβ histidine and tyrosine
residues can facilitate oligomerization and may play a role in both amyloid formation and Aβ neurotoxicity. Further work is
needed to determine the importance of Aβ oxidation in AD and the role of Aβ oxidation products and oxidative stress in disease
progression. The mechanisms of Aβ MCO are complex and multiple reaction products can form. Further study is needed to determine
the mechanisms by which Aβ MCO occursin vivo. In addition, new analytical methods are required to monitor the formation of Aβ MCO products formed during AD. The copper-H2O2 redox system provides a chemical model by which Aβ MCO can be studiedin vitro and can be used to produce oxidatively modified amino acid residues for use as standards in developing new analytical methods
to monitor Aβ MCO. 相似文献
7.
Alzheimer’s disease is characterized pathologically by senile plaques in the brain. The major component of senile plaques
is amyloid-β (Aβ), which is cleaved from Alzheimer’s Aβ protein precursor (AβPP). Recently, information regarding the cytoplasmic
tail of AβPP has started to emerge, opening up various insights into the physiological roles of AβPP and its pathological
role in Alzheimer’s disease. The cytoplasmic domain of AβPP shares the evolutionarily conserved GYENPTY motif, which binds
to a number of adaptor proteins containing the phosphotyrosine interaction domain (PID). Among the PID-containing proteins,
this article focuses on four groups of adaptor proteins of AβPP: Fe65, X11, mDab1, and c-Jun N-terminal kinase-interacting protein 1b/islet-brain 1.
These two authors contributed equally to this study. 相似文献
8.
Anna Colell Anna Fernández José C. Fernández-Checa 《Journal of bioenergetics and biomembranes》2009,41(5):417-423
The molecular mechanisms of Alzheimer’s disease (AD) are not fully understood. Extensive evidence from experimental models
has involved the overgeneration and accumulation of toxic amyloid β peptides (Aβ) in the onset and progression of the disease.
The amyloidogenic processing of amyloid precursor protein into pathogenic Aβ fragments is thought to occur in specific domains
of the plasma membrane and favored by cholesterol enrichment. Intracellular Aβ accumulation is known to induce oxidative stress,
predominantly via mitochondria targeting of toxic Aβ. Recent evidence using mouse models of cholesterol loading has demonstrated
that the specific mitochondrial cholesterol pool sensitizes neurons to Aβ-induced oxidant cell death and caspase-independent
apoptosis due to selective mitochondrial GSH (mGSH) depletion induced by cholesterol-mediated perturbation of mitochondrial
membrane dynamics. mGSH replenishment by permeable precursors such as glutathione ethyl ester protected against Aβ-mediated
neurotoxicity and inflammation. Thus, these novel data expand the pathogenic role of cholesterol in AD indicating that in
addition to fostering Aβ generation, mitochondrial cholesterol determines Aβ neurotoxicity via mGSH regulation. 相似文献
9.
Stephen D. Skaper Nicholas A. Evans Peter E. Soden Claudia Rosin Laura Facci Jill C. Richardson 《Neurochemical research》2009,34(12):2243-2250
Alzheimer’s disease is characterised by regional neuronal degeneration, synaptic loss, and the progressive deposition of the
4 kDa β-amyloid peptide (Aβ) in senile plaques and accumulation of tau protein as neurofibrillary tangles. Aβ derives from
the larger precursor molecule, amyloid precursor protein (APP) by proteolytic processing via β- and γ-secretases. While APP
expression is well documented in neurons and astrocytes, the case for oligodendrocytes is less clear. The latter cell type
is reported to express different isoforms of APP, and we have confirmed this observation by immunocytochemistry in cultures
of differentiated rat cortical oligodendrocytes. Moreover, by means of a sensitive electrochemiluminescent immunoassay employing
Aβ C-terminal specific antibodies, mature oligodendrocytes are shown to secrete the 40 and 42 amino acid Aβ species (Aβ40
and Aβ42). Secretion of Aβ peptides was reduced by incubating oligodendrocytes with α- and β-secretase inhibitors, or a γ-secretase
inhibitor. Disturbances of APP processing and/or synthesis in oligodendrocytes may account for some myelin disorders observed
in Alzheimer’s disease and other senile dementias. 相似文献
10.
Transglutaminase 2 silencing reduced the beta-amyloid-effects on the activation of human THP-1 cells
Monica Currò Nadia Ferlazzo Salvatore Condello Daniela Caccamo Riccardo Ientile 《Amino acids》2010,39(5):1427-1433
The aberrant expression and activation of transglutaminase 2 (TG2), the ubiquitous enzyme which catalyzes calcium-dependent
protein cross-linking reactions, has been reported in many inflammatory diseases. Chronic inflammation, mediated by prolonged
activation of brain-resident immunocompetent cells, appears to be involved in the pathogenesis of several age-related diseases,
such as Alzheimer’s disease. Given that increased TG2 expression has been observed in AD brains, this study was aimed to characterize
the role of TG2 in THP-1 monocytes stimulated with amyloid-beta (Aβ). Aβ1–42 treatment dose-dependently increased TG2 expression in THP-1 cells. In particular, a fivefold up-regulation of TG2, compared
with control cells, was observed in the presence of 0.5 μM Aβ1–42. At the same concentration, Aβ1–42 was able to promote monocyte maturation as suggested by increased expression of the cell surface antigen CD14 as well as
the adhesion-promoting factor fibronectin. The stimulation of THP-1 cells with Aβ1–42 also led to a significant up-regulation of tumor necrosis factor α (TNF-α) and matrix metalloproteinase 9 (MMP-9). Interestingly,
THP-1 cell transfection with small interfering RNA directed against TG2 was able to reduce Aβ1–42 increased levels of all the examined markers of monocyte maturation (CD14, fibronectin), and activation (TNF-α, MMP-9). These
results indicate that TG2 up-regulation is required for the functional THP-1 monocyte activation induced by Aβ1–42. This work suggests that TG2 inhibition may represent a therapeutic target to ameliorate the inflammation and progression
in Alzheimer’s disease. 相似文献
11.
Lambracht-Washington D Qu BX Fu M Anderson LD Stüve O Eagar TN Rosenberg RN 《Cellular and molecular neurobiology》2011,31(6):867-874
The pathogenesis of Alzheimer’s disease (AD) has been strongly associated with the accumulation of amyloid beta (Aβ) peptides
in brain, and immunotherapy targeting Aβ provides potential for AD prevention. A clinical trial in which AD patients were
immunized with Aβ42 peptide was stopped when 6% of participants showed meningoencephalitis, apparently due to an inflammatory
Th1 immune response. Previously, we and other have shown that Aβ42 DNA vaccination via gene gun generates a Th2 cellular immune
response, which was shown by analyses of the respective antibody isotype profiles. We also determined that in vitro T cell
proliferation in response to Aβ42 peptide re-stimulation was absent in DNA Aβ42 trimer-immunized mice when compared to Aβ42
peptide-immunized mice. To further characterize this observation prospectively and longitudinally, we analyzed the immune
response in wild-type mice after vaccination with Aβ42 trimer DNA and Aβ42 peptide with Quil A adjuvant. Wild-type mice were
immunized with short-term (1–3× vaccinations) or long-term (6× vacinations) immunization strategies. Antibody titers and isotype
profiles of the Aβ42 specific antibodies, as well as cytokine profiles and cell proliferation studies from this longitudinal
study were determined. Sufficient antibody titers to effectively reduce Aβ42, but an absent T cell proliferative response
and no IFNγ or IL-17 secretion after Aβ42 DNA trimer immunization minimizes the risk of inflammatory activities of the immune
system towards the self antigen Aβ42 in brain. Therefore, Aβ42 DNA trimer immunization has a high probability to be effective
and safe to treat patients with early AD. 相似文献
12.
Bruno Alies Vincent Pradines Isabelle Llorens-Alliot Stéphanie Sayen Emmanuel Guillon Christelle Hureau Peter Faller 《Journal of biological inorganic chemistry》2011,16(2):333-340
Metal ions such as zinc and copper can have dramatic effects on the aggregation kinetics of and the structures formed by several
amyloidogenic peptides/proteins. Depending on the identity of the amyloidogenic peptide/protein and the conditions, Zn(II)
and Cu(II) can promote or inhibit fibril formation, and in some cases these metal ions have opposite effects. To better understand
this modulation of peptide aggregation by metal ions, the impact of Zn(II) binding to three amyloidogenic peptides (Aβ14-23,
Aβ11-23, and Aβ11-28) on the formation and structure of amyloid-type fibrils was investigated. Zn(II) was able to accelerate
fibril formation for all three peptides as measured by thioflavin T fluorescence and transmission electron microscopy. The
effects of Zn(II) on Aβ11-23 and Aβ11-28 aggregation were very different compared with the effects of Cu(II), showing that
these promoting effects were metal-specific. X-ray absorption spectroscopy suggested that the Zn(II) binding to Aβ11-23 and
Aβ11-28 is very different from Cu(II) binding, but that the binding is similar in the case of Aβ14-23. A model is proposed
in which the different coordination chemistry of Zn(II) compared with Cu(II) explains the metal-specific effect on aggregation
and the difference between peptides Aβ14-23 and Aβ11-23/Aβ11-28. 相似文献
13.
Cryptotanshinione Inhibits β-Amyloid Aggregation and Protects Damage from β-Amyloid in SH-SY5Y Cells
The deposition of amyloid β-protein (Aβ) fibrils into plaques within the brain parenchyma and along cerebral blood vessels
is a hallmark of Alzheimer’s disease (AD). Aβ42 oligomers and fibrils cause the breakdown of neural circuits, neuronal death
and eventually dementia. Drugs that inhibit Aβ42 aggregation may be a novel direction in AD drug discovery. Cryptotanshinone
(CTS), an active component of the medicinal herb Salvia miltiorrhiza, has been shown to improve learning and memory in several
pharmacological models of AD. However, the effects of CTS on the Aβ aggregation and toxicity are unclear. The current work
shows the effectiveness of CTS on the inhibition of Aβ42 aggregation and toxicity to human neuroblastoma cells. In this study,
we demonstrated that CTS can inhibit Aβ42 spontaneous aggregation using thioflavin T fluorescence assay and transmission electron
microscopy. Furthermore, we investigated the effects of CTS on Aβ-induced oxidative cell death in cultured SH-SY5Y cells.
MTT and lactate dehydrogenase assays showed that CTS reduced the cytotoxicity induced by Aβ42. CTS also dramatically reduced
Aβ42-induced cellular apoptosis and increased level of reactive oxygen species in these cells. Our study suggests that CTS
may be useful in the inhibition or prevention of AD development and progression. 相似文献
14.
Luchsinger JA Tang MX Miller J Green R Mehta PD Mayeux R 《Neurochemical research》2007,32(4-5):775-781
Background Elevated plasma homocysteine and amyloid β (Aβ) have been associated with Alzheimer’s disease (AD). We investigated the cross-sectional
association between these biomarkers.
Methods We used linear regression to relate plasma homocysteine and Aβ adjusting for age, gender, creatinine, APOE-ε4, and ethnic
group in 327 persons aged 78 ± 6.6 years.
Results Plasma homocysteine correlated with age, serum creatinine, plasma Aβ40 and Aβ42, and was inversely correlated with serum vitamin
B12, and folate. Aβ42, but not Aβ40, was related to later development of dementia. Homocysteine was related to higher Aβ40
levels (coefficient = 2.0; P < 0.0001) and this association was attenuated after adjustment for creatinine (coefficient = 1.0; P < 0.0001). The crude association between homocysteine and Aβ42 was weaker (coefficient = 0.5; P = 0.01) and became non-significant after adjustment for creatinine (coefficient = 0.4; P = 0.06). These associations were unrelated to ethnicity, the presence of APOE-ε4 or dementia. Analyses by quartiles of homocysteine
showed that these association were driven primarily by the fourth quartile.
Conclusions Plasma homocysteine is directly related to Aβ40. The association with Aβ42 is not significant. These results seem to indicate
that homocysteine is related to aging but not specifically to AD.
Special issue dedicated to John P. Blass. 相似文献
15.
Adriana A Reyes Barcelo Francisco J Gonzalez-Velasquez Melissa A Moss 《Journal of biological engineering》2009,3(1):5-8
Background
Self-assembly of the amyloid-β peptide (Aβ) has been implicated in the pathogenesis of Alzheimer's disease (AD). As a result, synthetic molecules capable of inhibiting Aβ self-assembly could serve as therapeutic agents and endogenous molecules that modulate Aβ self-assembly may influence disease progression. However, increasing evidence implicating a principal pathogenic role for small soluble Aβ aggregates warns that inhibition at intermediate stages of Aβ self-assembly may prove detrimental. Here, we explore the inhibition of Aβ1–40 self-assembly by serum albumin, the most abundant plasma protein, and the influence of this inhibition on Aβ1–40 activation of endothelial cells for monocyte adhesion. 相似文献16.
Pathogenesis of Alzheimer’s disease (AD), which is characterised by accumulation of extracellular deposits of β-amyloid peptide
(Aβ) in the brain, has recently been linked to vascular disorders such as ischemia and stroke. Aβ is constantly produced in
the brain from amyloid precursor protein (APP) through its cleavage by β- and γ-secretases and certain Aβ species are toxic
for neurones. The brain has an endogenous mechanism of Aβ removal via proteolytic degradation and the zinc metalloproteinase
neprilysin (NEP) is a critical regulator of Aβ concentration. Down-regulation of NEP could predispose to AD. By comparing
the effects of hypoxia and oxidative stress on expression and activity of the Aβ-degrading enzyme NEP in human neuroblastoma
NB7 cells and rat primary cortical neurones we have demonstrated that hypoxia reduced NEP expression at the protein and mRNA
levels as well as its activity. On contrary in astrocytes hypoxia increased NEP mRNA expression.
Special issue dedicated to Dr. Moussa Youdim. 相似文献
17.
Amyloid beta-protein (Aβ) is the major component of senile plaques and cerebrovascular amyloid deposits in individuals with
Alzheimer’s disease. Aβ is known to increase free radical production in neuronal cells, leading to oxidative stress and cell
death. Recently, considerable attention has been focused on dietary antioxidants that are able to scavenge reactive oxygen
species (ROS), thereby offering protection against oxidative stress. Walnuts are rich in components that have anti-oxidant
and anti-inflammatory properties. The inhibition of in vitro fibrillization of synthetic Aβ, and solubilization of preformed
fibrillar Aβ by walnut extract was previously reported. The present study was designed to investigate whether walnut extract
can protect against Aβ-induced oxidative damage and cytotoxicity. The effect of walnut extract on Aβ-induced cellular damage,
ROS generation and apoptosis in PC12 pheochromocytoma cells was studied. Walnut extract reduced Aβ-mediated cell death assessed
by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction, and release of lactate dehydrogenase (membrane
damage), DNA damage (apoptosis) and generation of ROS in a concentration-dependent manner. These results suggest that walnut
extract can counteract Aβ-induced oxidative stress and associated cell death. 相似文献
18.
This study aims to discuss the effect of preventing pathological changes and cognitive degeneration of Tg2576 mice by inoculating
the subunit fragment of Aβ vaccine. Thirty-two Tg2576 mice were randomly divided into four groups, each having eight mice:
Group I, the control group, inoculated with adjuvants; Group II, the Aβ42 group, inoculated with Aβ42 vaccine; Group III, the Aβ1–15 group, inoculated with Aβ1–15 vaccine; and Group IV, the Aβ36–42 group, inoculated with Aβ36–42 vaccine. The titer of the serum antibody against Aβ42 (Group II) was significantly higher than that of the control group (Group I), and a low level of antibodies could be detected
in the brain homogenate in the three vaccine-inoculated groups. Morris water maze test showed that the Aβ42 group, Aβ1–15 group and Aβ36–42 group were obviously improved compared with the control group. The cultured splenocytes sampled from each group were induced
by Con A or their respective antigens, and the cell proliferation of the three vaccine-inoculated groups was significantly
higher than that of the control group. In the Aβ42 group, IL2 and IFN-γ were relatively low and IL4 and IL10 were relatively high. By contrast, IL4 and IL10 were much higher
in the Aβ1–15 group and IL2 and IFN-γ were much higher in the Aβ36–42 group. The immunohistochemical test showed a large number of senile plaques in the brain cortex and hippocampus of the mice
in the control group, no senile plaque in the brain of the Aβ1–15 group and Aβ42 group mice, and a small number of senile plaques in the brain of the Aβ36–42 group mice. The results suggest that the subunit fragment of Aβ1–15 vaccine could prevent not only cognitive and behavioral degeneration but also Aβ deposition and formation of senile plaques
in Tg2576 mice. 相似文献
19.
Aggregation of the amyloid β-peptide (Aβ) into insoluble fibrils is a key pathological event in Alzheimer’s disease. Cu(II)
and Zn(II) ions were reported to be able to induce Aβ aggregation at nearly physiological concentrations in vitro. In this
study, the binding modes of Cu(II) and Zn(II) in this process were explored by molecular modeling. In the pre-associated Aβ,
Nτ atom of imidazole ring of His14, O atom of carbonyl of main-chain and two O atoms of water occupied the four ligand positions
of the complex. While in the aggregated form of Aβ, the His13(N)–Metals–His14(N) bridges were formed through metal cross-linking
action. These results would be helpful to put insight on revealing the formation mechanism of pathogenic Aβ aggregates in
brain. 相似文献
20.
A<Emphasis Type="Bold">β</Emphasis> Upregulates and Colocalizes with LGI3 in Cultured Rat Astrocytes
Kimura N Ishii Y Suzaki S Negishi T Kyuwa S Yoshikawa Y 《Cellular and molecular neurobiology》2007,27(3):335-350
1. The leucine-rich glioma inactivated (LGI) family of genes encodes a leucine-rich repeat (LRR) protein, proteins that are
thought to be specifically involved in protein–protein and protein–matrix interactions. Since amyloid beta peptide (Aβ) has
been previously shown to induce the expression of another LRR-encoding gene in neural cells, we assessed how Aβ affects LGI
gene expression in rat primary cerebral cortical cultures and astrocyte cultures. Both RT-PCR and Western Blotting analyses
revealed that Aβ robustly induced the expression of LGI3 in rat astrocyte cultures.
2. Western Blotting analyses also showed that both glial fibrillary acidic protein (GFAP) and apolipoprotein E (ApoE) significantly
increased coincidentally with the Aβ-induced upregulation of LGI3. Immunocytochemistry showed that LGI3 colocalized with Aβ
at plasma membranes and also with internalized Aβ in astrocytes. These findings suggest that activated LGI3 may be involved
in the astroglial response against Aβ. 相似文献