833 results match your criteria abeta binds

Amyloid β and Amyloid Precursor Protein Synergistically Suppress Large-Conductance Calcium-Activated Potassium Channel in Cortical Neurons.

Front Aging Neurosci 2021 3;13:660319. Epub 2021 Jun 3.

Department of Physiology, Kanazawa Medical University, Ishikawa, Japan.

Intracellular amyloid β (Aβ) injection suppresses the large-conductance calcium-dependent potassium (BK) channel in cortical pyramidal cells from wild-type (WT) mice. In 3xTg Alzheimer's disease (AD) model mice, intraneuronal Aβ is genetically programed to accumulate, which suppresses the BK channel. However, the mode of BK channel suppression remained unclarified. Read More

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Pseudogene ACTBP2 increases blood-brain barrier permeability by promoting KHDRBS2 transcription through recruitment of KMT2D/WDR5 in Aβ microenvironment.

Cell Death Discov 2021 Jun 14;7(1):142. Epub 2021 Jun 14.

Department of Neurobiology, School of life Sciences, China Medical University, Shenyang, China.

The blood-brain barrier (BBB) has a vital role in maintaining the homeostasis of the central nervous system (CNS). Changes in the structure and function of BBB can accelerate Alzheimer's disease (AD) development. β-Amyloid (Aβ) deposition is the major pathological event of AD. Read More

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Analysis of the role of Purα in the pathogenesis of Alzheimer's disease based on RNA-seq and ChIP-seq.

Sci Rep 2021 Jun 9;11(1):12178. Epub 2021 Jun 9.

Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of the National Key Laboratory, Ningxia Medical University, Yinchuan, China.

Purine rich element binding protein A (Purα), encoded by the Purα gene, is an important transcriptional regulator that binds to DNA and RNA and is involved in processes such as DNA replication and RNA translation. Purα also plays an important role in the nervous system. To identify the function of Pura, we performed RNA sequence (RNA-seq) analysis of Purɑ-KO mouse hippocampal neuron cell line (HT22) to analyze the effect of Purα deletion on neuronal expression profiles. Read More

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Aβ receptors specifically recognize molecular features displayed by fibril ends and neurotoxic oligomers.

Nat Commun 2021 06 8;12(1):3451. Epub 2021 Jun 8.

Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.

Several cell-surface receptors for neurotoxic forms of amyloid-β (Aβ) have been described, but their molecular interactions with Aβ assemblies and their relative contributions to mediating Alzheimer's disease pathology have remained uncertain. Here, we used super-resolution microscopy to directly visualize Aβ-receptor interactions at the nanometer scale. We report that one documented Aβ receptor, PrP, specifically inhibits the polymerization of Aβ fibrils by binding to the rapidly growing end of each fibril, thereby blocking polarized elongation at that end. Read More

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A screened PirB antagonist peptide antagonizes Aβ-mediated inhibition of neurite outgrowth in vitro.

Appl Microbiol Biotechnol 2021 Jun 1;105(11):4649-4662. Epub 2021 Jun 1.

Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, China.

Alzheimer's disease (AD) is a type of progressive neurodegenerative disease, and amyloid β-protein 42 (Aβ) serves an important role in the pathological process of development of AD. Paired immunoglobulin-like receptor B (PirB) is a functional receptor for myelin inhibitors of neuron regeneration in the CNS, and it has also been identified to function as a high-affinity receptor for Aβ. Here, we used a phage display to identify a specific PirB antagonist peptide 11(PAP11, PFRLQLS), which could reverse Aβ-induced neurotoxicity and promote neurite outgrowth in vitro. Read More

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Defects in Protein Folding and/or Quality Control Cause Protein Aggregation in the Endoplasmic Reticulum.

Prog Mol Subcell Biol 2021 ;59:115-143

Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.

Protein aggregation is now a common hallmark of numerous human diseases, most of which involve cytosolic aggregates including Aβ (AD) and ⍺-synuclein (PD) in Alzheimer's disease and Parkinson's disease. However, it is also evident that protein aggregation can also occur in the lumen of the endoplasmic reticulum (ER) that leads to specific diseases due to loss of protein function or detrimental effects on the host cell, the former is inherited in a recessive manner where the latter are dominantly inherited. However, the mechanisms of protein aggregation, disaggregation and degradation in the ER are not well understood. Read More

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January 2021

In vivo micro computed tomography detection and decrease in amyloid load by using multifunctionalized gold nanorods: a neurotheranostic platform for Alzheimer's disease.

Biomater Sci 2021 Jun 13;9(11):4178-4190. Epub 2021 May 13.

Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.

The development and use of nanosystems is an emerging strategy for the diagnosis and treatment of a broad number of diseases, such as Alzheimer's disease (AD). Here, we developed a neurotheranostic nanosystem based on gold nanorods (GNRs) that works as a therapeutic peptide delivery system and can be detected in vivo for microcomputed tomography (micro-CT), being a diagnostic tool. GNRs functionalized with the peptides Ang2 (a shuttle to the Central Nervous System) and D1 (that binds to the Aβ peptide, also inhibiting its aggregation) allowed detecting differences in vivo between wild type and AD mice (APPswe/PSEN1dE9) 15 minutes after a single dose by micro-CT. Read More

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Non-phosphorylated Tau slows down Aβ aggregation, binds to Aβ oligomers and reduces Aβ toxicity.

J Biol Chem 2021 Apr 15:100664. Epub 2021 Apr 15.

Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy. Electronic address:

The formation of neurofibrillary tangles and amyloid plaques accompanies the progression of Alzheimer's disease (AD). Tangles are made of fibrillar aggregates formed by the microtubule-associated protein tau, while plaques comprise fibrillar forms of amyloid-β (Aβ). Both form toxic oligomers during aggregation, and are thought to interact synergistically to each promote the accumulation of the other. Read More

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Curcumin and Homotaurine Suppress Amyloid-β Aggregation in Synthetic Brain Membranes.

ACS Chem Neurosci 2021 04 7;12(8):1395-1405. Epub 2021 Apr 7.

Department of Physics and Astronomy, McMaster University, Hamilton, ON L8S 4M1, Canada.

Amyloid-β (Aβ) peptides spontaneously aggregate into β- and cross-β-sheets in model brain membranes. These nanometer sized can fuse into larger micrometer sized clusters and become extracellular and serve as nuclei for further plaque and fibril growth. Curcumin and homotaurine represent two different types of Aβ aggregation inhibitors. Read More

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SARS-CoV-2 spike protein interactions with amyloidogenic proteins: Potential clues to neurodegeneration.

Biochem Biophys Res Commun 2021 05 24;554:94-98. Epub 2021 Mar 24.

Amity Institute of Neuropsychology & Neurosciences, Amity University, Noida, UP, 201303, India. Electronic address:

The post-infection of COVID-19 includes a myriad of neurologic symptoms including neurodegeneration. Protein aggregation in brain can be considered as one of the important reasons behind the neurodegeneration. SARS-CoV-2 Spike S1 protein receptor binding domain (SARS-CoV-2 S1 RBD) binds to heparin and heparin binding proteins. Read More

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A nuclear factor-kappa B inhibiting peptide suppresses innate immune receptors and gliosis in a transgenic mouse model of Alzheimer's disease.

Biomed Pharmacother 2021 Jun 20;138:111405. Epub 2021 Mar 20.

Department of Oral Pathology, Medicine and Radiology, Indiana University School of Dentistry, United States; Provaidya LLC, Indianapolis, IN, United States. Electronic address:

A disproportionate increase in activated nuclear factor-kappa B (NF-κB) has been shown to drive the Aβ deposition, neuroinflammation and neurodegeneration in Alzheimer's disease (AD). Hence, selective targeting of activated p65 represents an attractive therapeutic approach for AD. Glucocorticoid induced leucine zipper (GILZ) is a NF-κB interactant that binds and sequesters the activated p65 in the cytoplasm. Read More

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Aggregation of Aβ40/42 chains in the presence of cyclic neuropeptides investigated by molecular dynamics simulations.

PLoS Comput Biol 2021 Mar 12;17(3):e1008771. Epub 2021 Mar 12.

Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Canada.

Alzheimer's disease is associated with the formation of toxic aggregates of amyloid beta (Aβ) peptides. Despite tremendous efforts, our understanding of the molecular mechanisms of aggregation, as well as cofactors that might influence it, remains incomplete. The small cyclic neuropeptide somatostatin-14 (SST14) was recently found to be the most selectively enriched protein in human frontal lobe extracts that binds Aβ42 aggregates. Read More

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Albumin Alters the Conformational Ensemble of Amyloid-β by Promiscuous Interactions: Implications for Amyloid Inhibition.

Huisi Xie Cong Guo

Front Mol Biosci 2020 23;7:629520. Epub 2021 Feb 23.

Department of Physics and International Centre for Quantum and Molecular Structures, College of Sciences, Shanghai University, Shanghai, China.

Human serum albumin (HSA) is a key endogenous inhibitor of amyloid-β (Αβ) aggregation. In vitro HSA inhibits Aβ fibrillization and targets multiple species along the aggregation pathway including monomers, oligomers, and protofibrils. Amyloid inhibition by HSA has both pathological implications and therapeutic potential, but the underlying molecular mechanism remains elusive. Read More

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February 2021

Binding of Amyloid β(1-42)-Calmodulin Complexes to Plasma Membrane Lipid Rafts in Cerebellar Granule Neurons Alters Resting Cytosolic Calcium Homeostasis.

Int J Mol Sci 2021 Feb 17;22(4). Epub 2021 Feb 17.

Instituto de Biomarcadores de Patologías Moleculares, Universidad de Extremadura, 06006 Badajoz, Spain.

Lipid rafts are a primary target in studies of amyloid β (Aβ) cytotoxicity in neurons. Exogenous Aβ peptides bind to lipid rafts, which in turn play a key role in Aβ uptake, leading to the formation of neurotoxic intracellular Aβ aggregates. On the other hand, dysregulation of intracellular calcium homeostasis in neurons has been observed in Alzheimer's disease (AD). Read More

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February 2021

Tuning the conformation of G-quadruplexes by sodium and potassium ions: application to photometric and fluorometric determination of amyloid β(1-40).

Mikrochim Acta 2021 Feb 23;188(3):98. Epub 2021 Feb 23.

Department of Physical and Chemical Testing, Shandong Center for Disease Control and Prevention, Jinan, People's Republic of China.

A dual channel method is described for the determination of the amyloid-β peptide Aβ(1-40) that is associated with Alzheimer's disease. The method exploits (a) conformational changes of a G-quadruplex that are triggered by Na and K ions and (b) the strong affinity between Aβ(1-40) and Cu. A G-quadruplex DNA forms an antiparallel structure in the presence of Na and can catalyze the oxidation of tetramethylbenzidine by HO system in the presence of Cu to form a visible blue color. Read More

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February 2021

Smallest Secondary Nucleation Competent Aβ Aggregates Probed by an ATP-Independent Molecular Chaperone Domain.

Biochemistry 2021 03 23;60(9):678-688. Epub 2021 Feb 23.

Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, 14183 Huddinge, Sweden.

Protein oligomerization is a commonly encountered strategy by which the functional repertoire of proteins is increased. This, however, is a double-edged sword strategy because protein oligomerization is notoriously difficult to control. Living organisms have therefore developed a number of chaperones that prevent protein aggregation. Read More

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CERT reduces C16 ceramide, amyloid-β levels, and inflammation in a model of Alzheimer's disease.

Alzheimers Res Ther 2021 02 17;13(1):45. Epub 2021 Feb 17.

Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, the Netherlands.

Background: Dysregulation of ceramide and sphingomyelin levels have been suggested to contribute to the pathogenesis of Alzheimer's disease (AD). Ceramide transfer proteins (CERTs) are ceramide carriers which are crucial for ceramide and sphingomyelin balance in cells. Extracellular forms of CERTs co-localize with amyloid-β (Aβ) plaques in AD brains. Read More

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February 2021

Multi-target inhibition ability of neohesperidin dictates its neuroprotective activity: Implication in Alzheimer's disease therapeutics.

Int J Biol Macromol 2021 Apr 11;176:315-324. Epub 2021 Feb 11.

Department of Microbiology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, India. Electronic address:

The polygenic nature of Alzheimer's disease (AD) and cross-talk between several signaling cascades make it harder to decode the disease pathogenesis. β-secretase (BACE1) works upstream in the amyloidogenic processing of amyloid precursor protein (APP) to generate Aβ that rapidly aggregates to form fibrils, the most abundant component of plaques observed in AD brains. Here, we report dual inhibition of BACE1 and Aβ aggregation by neohesperidin, a flavonoid glycoconjugate, using multi-spectroscopic approaches, force microscopy, molecular modeling, and validated the potency in SH-SY5Y neuroblastoma cell lines. Read More

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Keto form of curcumin derivatives strongly binds to Aβ oligomers but not fibrils.

Biomaterials 2021 03 23;270:120686. Epub 2021 Jan 23.

Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, 520-2192, Japan. Electronic address:

The accumulation of β-amyloid (Aβ) aggregates in the brain occurs early in the progression of Alzheimer's disease (AD), and non-fibrillar soluble Aβ oligomers are particularly neurotoxic. During binding to Aβ fibrils, curcumin, which can exist in an equilibrium state between its keto and enol tautomers, exists predominantly in the enol form, and binding activity of the keto form to Aβ fibrils is much weaker. Here we described the strong binding activity the keto form of curcumin derivative Shiga-Y51 shows for Aβ oligomers and its scant affinity for Aβ fibrils. Read More

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Serotonin and Melatonin Show Different Modes of Action on Aβ Protofibril Destabilization.

ACS Chem Neurosci 2021 02 3;12(4):799-809. Epub 2021 Feb 3.

College of Physical Education and Training, Shanghai University of Sport, 399 Chang Hai Road, Shanghai 200438, People's Republic of China.

Alzheimer's disease (AD) is associated with the aberrant self-assembly of amyloid-β (Aβ) protein into fibrillar deposits. The disaggregation of Aβ fibril is believed as one of the major therapeutic strategies for treating AD. Previous experimental studies reported that serotonin (Ser), one of the indoleamine neurotransmitters, and its derivative melatonin (Mel) are able to disassemble preformed Aβ fibrils. Read More

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February 2021

Deletion of LRP1 From Astrocytes Modifies Neuronal Network Activity in an Model of the Tripartite Synapse.

Front Cell Neurosci 2020 14;14:567253. Epub 2021 Jan 14.

Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, Bochum, Germany.

The low-density lipoprotein receptor-related protein 1 (LRP1) is a transmembrane receptor that binds over 40 potential ligands and is involved in processes such as cell differentiation, proliferation, and survival. LRP1 is ubiquitously expressed in the organism and enriched among others in blood vessels, liver, and the central nervous system (CNS). There, it is strongly expressed by neurons, microglia, immature oligodendrocytes, and astrocytes. Read More

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January 2021

Deciphering the Disaggregation Mechanism of Amyloid Beta Aggregate by 4-(2-Hydroxyethyl)-1-Piperazinepropanesulfonic Acid Using Electrochemical Impedance Spectroscopy.

Sensors (Basel) 2021 Jan 25;21(3). Epub 2021 Jan 25.

Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Korea.

Aggregation of amyloid-β (aβ) peptides into toxic oligomers, fibrils, and plaques is central in the molecular pathogenesis of Alzheimer's disease (AD) and is the primary focus of AD diagnostics. Disaggregation or elimination of toxic aβ aggregates in patients is important for delaying the progression of neurodegenerative disorders in AD. Recently, 4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid (EPPS) was introduced as a chemical agent that binds with toxic aβ aggregates and transforms them into monomers to reduce the negative effects of aβ aggregates in the brain. Read More

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January 2021

Early neuroinflammation is associated with lower amyloid and tau levels in cognitively normal older adults.

Brain Behav Immun 2021 05 22;94:299-307. Epub 2021 Jan 22.

Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, United States; Alzheimer Disease Research Center, Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, United States. Electronic address:

CNS inflammation is a key factor in Alzheimer's Disease (AD), but its relation to pathological Aβ, tau, and APOE4 is poorly understood, particularly prior to the onset of cognitive symptoms. To better characterize early relationships between inflammation, APOE4, and AD pathology, we assessed correlations between cerebrospinal fluid (CSF) inflammatory markers and brain levels of Aβ and tau in cognitively normal older adults. Each participant received a lumbar puncture to collect and quantify CSF levels of TNFα, IL-6, IL-8, and IL-10, a T1-weighted MRI, and PET scanning with [F]flortaucipir (FTP; n = 57), which binds to tau tangles and/or [F]florbetapir (FBP; n = 58), which binds to Aβ. Read More

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Effects of Ions and Small Compounds on the Structure of Aβ Monomers.

J Phys Chem B 2021 02 22;125(4):1085-1097. Epub 2021 Jan 22.

Department of Physics, New Jersey Institute of Technology, Newark, New Jersey 07102-1982, United States.

Aggregation of amyloid-β (Aβ) proteins in the brain is a hallmark of Alzheimer's disease. This phenomenon can be promoted or inhibited by adding small molecules to the solution where Aβ is embedded. These molecules affect the ensemble of conformations sampled by Aβ monomers even before aggregation starts. Read More

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February 2021

Chronic administration of Tat-GluR23Y ameliorates cognitive dysfunction targeting CREB signaling in rats with amyloid beta neurotoxicity.

Metab Brain Dis 2021 04 9;36(4):701-709. Epub 2021 Jan 9.

Cellular & Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, 8th Km of Rasht -Tehran road, Guilan University Complex, Rasht, Guilan, 41996-13769, Iran.

Alzheimer's disease (AD) is behaviorally characterized by memory impairments, and pathologically by amyloid β1-42 (Aβ1-42) plaques and tangles. Aβ binds to excitatory synapses and disrupts their transmission due to dysregulation of the glutamate receptors. Here we hypothesized that chronic inhibition of the endocytosis of AMPA receptors together with GluN2B subunit of NMDA receptors might improve cognition deficit induced by Aβ(1-42) neurotoxicity. Read More

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Modified Snake α-Neurotoxin Averts β-Amyloid Binding to α7 Nicotinic Acetylcholine Receptor and Reverses Cognitive Deficits in Alzheimer's Disease Mice.

Mol Neurobiol 2021 May 8;58(5):2322-2341. Epub 2021 Jan 8.

Drug Discovery Laboratory, The Azrieli Faculty of Medicine, Bar-Ilan University, 1311502, Safed, Israel.

Alzheimer's disease (AD) is the most common cause of senile dementia and one of the greatest medical, social, and economic challenges. According to a dominant theory, amyloid-β (Aβ) peptide is a key AD pathogenic factor. Aβ-soluble species interfere with synaptic functions, aggregate gradually, form plaques, and trigger neurodegeneration. Read More

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Curcumin-Pluronic Nanoparticles: A Theranostic Nanoformulation for Alzheimer's Disease.

Crit Rev Biomed Eng 2020 ;48(3):153-168

Institute for Lasers, Photonics and Biophotonics, Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, New York, USA.

There is an increased need of drugs with multifunctional properties for visualization of β-amyloid (Aβ) plaques for early diagnosis and treatment of Alzheimer's disease (AD). Curcumin (Cur) is a potent antiamyloid, antiinflammatory, and antiapoptotic natural product that has been used to treat several neurodegenerative diseases, including AD. Curcumin can reduce amyloid burden, rescue neuronal damage, and restore normal cognitive and sensory motor functions in AD. Read More

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January 2020

iPSC-Derived Microglia for Modeling Human-Specific DAMP and PAMP Responses in the Context of Alzheimer's Disease.

Int J Mol Sci 2020 Dec 18;21(24). Epub 2020 Dec 18.

Department of Neurology, State University of New York at Buffalo, 875 Ellicott St., Buffalo, NY 14203, USA.

Neuroinflammation in Alzheimer's disease (AD) has been the focus for identifying targetable pathways for drug development. The role of amyloid beta (Aβ), a prototype of damage-associated molecular patterns (DAMPs), has been implicated in triggering an inflammatory response. As alpha7 nicotinic acetylcholine receptor (α7 nAChR) binds Aβ with high affinity, α7 nAChR may play a role in Aβ-induced neuroinflammation. Read More

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December 2020

C/EBPβ is a key transcription factor for APOE and preferentially mediates ApoE4 expression in Alzheimer's disease.

Mol Psychiatry 2020 Dec 18. Epub 2020 Dec 18.

Department of Pathophysiology, Key Laboratory of Ministry of Education of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The apolipoprotein E ε4 (APOE4) allele is a major genetic risk factor for Alzheimer's disease (AD), and its protein product, ApoE4, exerts its deleterious effects mainly by influencing amyloid-β (Aβ) and Tau (neurofibrillary tangles, NFTs) deposition in the brain. However, the molecular mechanism dictating its expression during ageing and in AD remains incompletely clear. Here we show that C/EBPβ acts as a pivotal transcription factor for APOE and mediates its mRNA levels in an age-dependent manner. Read More

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December 2020

Danger-Sensing/Patten Recognition Receptors and Neuroinflammation in Alzheimer's Disease.

Int J Mol Sci 2020 Nov 27;21(23). Epub 2020 Nov 27.

Section of Human Histology & Embryology, Department of Surgery, Dentistry, Pediatrics, and Gynecology, University of Verona, Verona, 37134 Venetia, Italy.

Fibrillar aggregates and soluble oligomers of both Amyloid-β peptides (Aβs) and hyperphosphorylated Tau proteins (p-Tau-es), as well as a chronic neuroinflammation are the main drivers causing progressive neuronal losses and dementia in Alzheimer's disease (AD). However, the underlying pathogenetic mechanisms are still much disputed. Several endogenous neurotoxic ligands, including Aβs, and/or p-Tau-es activate innate immunity-related danger-sensing/pattern recognition receptors (PPRs) thereby advancing AD's neuroinflammation and progression. Read More

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November 2020