Alzheimers Disease: Cellular and Molecular Aspects of Amyloid beta: 38 (Subcellular Biochemistry)

Alzheimer's Disease: Cellular and Molecular Aspects of Amyloid beta ( Subcellular Biochemistry): Series: Subcellular Biochemistry ( Book 38).
Table of contents

J Pineal Res 24 2: Inhibition of Alzheimer's disease beta-amyloid aggregation, neurotoxicity, and in vivo deposition by nitrophenols: A structural motif of acetylcholinesterase that promotes amyloid beta-peptide fibril formation. Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease.

TDP43 and Alzheimer's Study

Chondroitin sulfate proteoglycans are associated with the lesions of Alzheimer's disease. Exp Neurol 2: Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem 76 1: ApoE protects cortical neurones against neurotoxicity induced by the non-fibrillar C-terminal domain of the amyloid-beta peptide. Alpha2-macroglobulin attenuates beta-amyloid peptide formation and associated neurotoxicity of cultured fetal rat cortical neurons.

J Neurochem 70 3: Alpha 1-antichymotrypsin regulates Alzheimer beta-amyloid peptide fibril formation. Apolipoprotein E is a kinetic but not a thermodynamic inhibitor of amyloid formation: Protein dynamics, folding and misfolding: Biophys J 60 5: J Neurochem 59 4: Alpha 1-antichymotrypsin binding to Alzheimer A beta peptides is sequence specific and induces fibril disaggregation in vitro. J Neurochem 61 1: Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides.

Implications for drug development. J Biol Chem 9: N-terminal EFRH sequence of Alzheimer's beta- amyloid peptide represents the epitope of its anti-aggregating antibodies. J Neuroimmunol 88 High affinity binding of monoclonal antibodies to the sequential epitope EFRH of beta-amyloid peptide is essential for modulation of fibrillar aggregation.

INTRODUCTION

J Neuroimmunol 95 Modulation of Alzheimer's beta-amyloid neurotoxicity by site-directed single-chain antibody. J Neuroimmunol Processing of Alzheimer A beta-amyloid precursor protein: Int Rev Neurobiol Aging renders the brain vulnerable to amyloid beta-protein neurotoxicity. Nat Med 4 7: From molecular structure to Alzheimer therapy. Jpn J Pharmacol 74 3: Biochem Biophys Res Commun 3: Testosterone reduces neuronal secretion of Alzheimer's beta-amyloid peptides.

Low concentrations of estradiol reduce beta-amyloid -induced toxicity, lipid peroxidation and glucose utilization in human SK-N-SH neuroblastoma cells. Brain Res 1: Congo red inhibits proteoglycan and serum amyloid P binding to amyloid beta fibrils. J Neurochem 70 1: The presenilins in Alzheimer's disease-proteolysis holds the key. Amyloid, the presenilins and Alzheimer's disease. Trends Neurosci 20 4: Complement association with neurons and beta-amyloid deposition in the brains of aged individuals with Down Syndrome.

Neurobiol Dis 8 2: Inhibition of beta-amyloid formation identifies proteolytic precursors and subcellular site of catabolism. Structure of the protease domain of memapsin 2 beta-secretase complexed with inhibitor. Estrogen protects neuronal cells from amyloid beta-induced apoptotic cell death.

Zinc-induced Alzheimer's Abeta aggregation is mediated by conformational factors. Alpha2-macroglobulin associates with beta-amyloid peptide and prevents fibril formation. Structure of beta-crystallite assemblies formed by Alzheimer beta-amyloid protein analogues: Biophys J 64 2: Identification of the major Abetadegrading catabolic pathway in brain parenchyma: Nat Med 6 2: Estrogen regulates metabolism of Alzheimer amyloid beta precursor protein. A specific structural interaction of Alzheimer's peptide A beta with alpha 1-antichymotrypsin. Nat Struct Biol 3 8: Alzheimer's peptide Abeta binds to two beta-sheets of alpha1-antichymotrypsin and transforms it from inhibitor to substrate.


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A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. Biochem Biophys Res Commun 1: The precursor of Alzheimer's disease amyloid A4 protein resembles a cell surface receptor. A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: Entactin-induced inhibition of human amyloid beta-protein fibril formation in vitro.

Neurosci Lett 2: Cell-type and amyloid precursor protein-type specific inhibition of A beta release by bafilomycin A1, a selective inhibitor of vacuolar ATPases. J Biol Chem 6: Apolipoprotein A-I directly interacts with amyloid precursor protein and inhibits A beta aggregation and toxicity. Iron released from transferrin at acidic pH can catalyse the oxidation of low density lipoprotein. FEBS Lett 1: Alpha 2-macroglobulin-mediated degradation of amyloid beta Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type.

Estrogen enhances uptake of amyloid beta-protein by microglia derived from the human cortex. J Neurochem 75 4: Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein. Histidine is a crucial residue in the zinc ion-induced aggregation of the A beta peptide of Alzheimer's disease. Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red.

Copper, iron and zinc in Alzheimer's disease senile plaques. J Neurol Sci 1: Is the binding of beta-amyloid protein to antichymotrypsin in Alzheimer plaques mediated by a beta-strand insertion? Mice deficient in BACE1, the Alzheimer's beta-secretase, have normal phenotype and abolished beta-amyloid generation.

Nat Neurosci 4 3: Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments. Estrogen induces a rapid secretion of amyloid beta precursor protein via the mitogen-activated protein kinase pathway. Eur J Biochem Neuronal origin of a cerebral amyloid: EMBO J 4 Apolipoprotein J and Alzheimer's amyloid beta solubility.

Membrane disruption by Alzheimer beta-amyloid peptides mediated through specific binding to either phospholipids or gangliosides. Characterization of the interactions of Alzheimer beta-amyloid peptides with phospholipid membranes. Eur J Biochem 2: Phosphatidylinositol and inositol involvement in Alzheimer amyloid-beta fibril growth and arrest. J Mol Biol 1: Interactions of Alzheimer amyloid-beta peptides with glycosaminoglycans effects on fibril nucleation and growth. Eur J Biochem 3: Inositol stereoisomers stabilize an oligomeric aggregate of Alzheimer amyloid beta peptide and inhibit abeta -induced toxicity.

Interaction of the anthracycline 4'-iodo-4'-deoxydoxorubicin with amyloid fibrils: Differential effects of apolipoprotein E isoforms on metal-induced aggregation of A beta using physiological concentrations. Laminin inhibits A beta 40 fibril formation promoted by apolipoprotein E4 in vitro.

Estrogen blocks neurotoxic effects of beta-amyloid and induces neurite extension on B cells. Neurosci Lett 3: Toward the characterization and identification of gamma-secretases using transition-state analogue inhibitors. A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease.


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    • Astroglial expression of human alpha 1 -antichymotrypsin enhances alzheimer-like pathology in amyloid protein precursor transgenic mice. Am J Pathol 6: Insulysin hydrolyzes amyloid beta peptides to products that are neither neurotoxic nor deposit on amyloid plaques. J Neurosci 20 Alphaantichymotrypsin promotes beta-sheet amyloid plaque deposition in a transgenic mouse model of Alzheimer's disease. J Neurosci 21 5: Regulation of APP cleavage by alpha-, beta- and gamma-secretases. Clusterin apoJ alters the aggregation of amyloid beta-peptide A beta and forms slowly sedimenting beta complexes that cause oxidative stress.

    Exp Neurol 1: Melatonin prevents death of neuroblastoma cells exposed to the Alzheimer amyloid peptide. J Neurosci 17 5: Inhibition of Alzheimer beta-fibrillogenesis by melatonin. Alzheimer beta protein mediated oxidative damage of mitochondrial DNA: J Pineal Res 27 4: An assessment of the antioxidant and the antiamyloidogenic properties of melatonin: J Neural Transm 2: Microglial cells internalize aggregates of the Alzheimer's disease amyloid beta-protein via a scavenger receptor.

    Neurodegeneration induced by beta-amyloid peptides in vitro: J Neurosci 13 4: Beta-sheet breaker peptide inhibitor of Alzheimer's amyloidogenesis with increased blood-brain barrier permeability and resistance to proteolytic degradation in plasma. J Neurobiol 39 3: Alzheimer disease-when and why? Nat Genet 19 4: Alpha2-macroglobulin enhances the clearance of endogenous soluble beta-amyloid peptide via low-density lipoprotein receptor-related protein in cortical neurons. J Neurochem 73 4: Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease.

    Nat Med 2 8: Presenilin-1 and -2 are molecular targets for gamma-secretase inhibitors. Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer's disease. Annu Rev Cell Biol The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer's disease. Trends Cell Biol 8 Translating cell biology into therapeutic advances in Alzheimer's disease.

    Nature Suppl: Calcium ionophore A specifically decreases the secretion of beta-secretase cleaved amyloid precursor protein during apoptosis in primary rat cortical cultures. J Neurosci Res 63 5: Postmenopausal estrogen replacement therapy and the risk of Alzheimer disease. Arch Neurol 58 3: Amyloid beta protein A beta removal by neuroglial cells in culture. Neurobiol Aging 16 5: Neprilysin degrades both amyloid beta peptides and most rapidly and efficiently among thiorphan- and phosphoramidon-sensitive endopeptidases. In vivo reversal of amyloid-beta lesions in rat brain.

    J Neuropathol Exp Neurol 59 1: Purification and cloning of amyloid precursor protein beta-secretase from human brain. Annu Rev Biochem Daily variation in the concentration of melatonin and 5-methoxytryptophol in the human pineal gland: Alzheimer's disease and the amyloid beta protein: What is the role of amyloid?

    J Neurochem 73 2: The presence of heparan sulfate proteoglycans in the neuritic plaques and congophilic angiopathy in Alzheimer's disease. Am J Pathol 3: Peripheral distribution of dermatan sulfate proteoglycans decorin in amyloid-containing plaques and their presence in neurofibrillary tangles of Alzheimer's disease. J Histochem Cytochem 40 1: Differential binding of vascular cell-derived proteoglycans perlecan, biglycan, decorin, and versican to the beta-amyloid protein of Alzheimer's disease.

    Identification in immunolocalization of a new class of proteoglycan keratan sulfate to the neuritic plaques of Alzheimer's disease. Monoclonal antibodies inhibit in vitro fibrillar aggregation of the Alzheimer beta-amyloid peptide. Disaggregation of Alzheimer beta-amyloid by site-directed mAb. Inhibition of Alzheimer's amyloidosis by peptides that prevent beta-sheet conformation. Beta-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: Reversion of prion protein conformational changes by synthetic beta-sheet breaker peptides.

    Antibody clears senile plaques. J Immunol Acetylcholinesterase in Alzheimer's disease. Mech Ageing Dev Alzheimer beta-amyloid peptide Self-association of beta-amyloid peptide in solution and binding to lipid membranes. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulin-degrading enzyme.

    J Neurosci 20 5: The role of amyloid in the pathogenesis of Alzheimer's disease. Biol Chem 9: Heparin-binding properties of the amyloidogenic peptides Abeta and amylin. Dependence on aggregation state and inhibition by Congo red. Multivalent binding of complement protein C1Q to the amyloid beta-peptide A beta promotes the nucleation phase of A beta aggregation.

    Peptides homologous to the amyloid protein of Alzheimer's disease containing a glutamine for glutamic acid substitution have accelerated amyloid fibril formation. An ApoE-Abeta inhibition complex in Abeta fibril extension. Chem Biol 3 Estrogen reduces neuronal generation of Alzheimer beta-amyloid peptides.

    Nat Med 4 4: Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity. Manipulating the amyloid-beta aggregation pathway with chemical chaperones. Mechanisms of neuronal degeneration in Alzheimer's disease. Effect of human endopeptidase Immunohistochemical localization of neprilysin in the human cerebral cortex: Membrane localization of endopeptidase Abeta-degrading endopeptidase, neprilysin, in mouse brain: Region-specific reduction of a beta-degrading endopeptidase, neprilysin, in mouse hippocampus upon aging.

    Journal of Neuroscience Research. Biochemical identification of the neutral endopeptidase family member responsible for the catabolism of amyloid beta peptide in the brain. Journal of Biochemistry Tokyo ; Neprilysin regulates amyloid Beta peptide levels. Journal of Alzheimer's Disease. Human neprilysin is capable of degrading amyloid beta peptide not only in the monomeric form but also the pathological oligomeric form.

    Effects of neprilysin chimeric proteins targeted to subcellular compartments on amyloid beta peptide clearance in primary neurons. Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Anti-amyloid activity of neprilysin in plaque-bearing mousemodels of Alzheimer's disease.

    Neprilysin gene transfer reduces human amyloid pathology in transgenic mice. The Journal of Neuroscience. Prevalence of Alzheimer's disease and vascular dementia: Quantitation of amyloid beta-protein A beta in the cortex during aging and in Alzheimer's disease. The American Journal of Bathology. Identification of normal and pathological aging in prospectively studied nondemented elderly humans.

    Aging-related down-regulation of neprilysin, a putative beta-amyloid-degrading enzyme, in transgenic Tg Alzheimer-like mouse brain is accompanied by an astroglial upregulation in the vicinity of betaamyloid plaques. Age- and region dependent alterations in Abeta-degrading enzymes: Reduced neprilysin in high plaque areas of Alzheimer brain: Relationship between beta amyloid peptide generating molecules and neprilysin in Alzheimer disease and normal brain.

    Oxidized neprilysin in aging and Alzheimer's disease brains. Cerebrospinal fluid neprilysin is reduced in prodromal Alzheimer's disease. Declining expression of neprilysin in Alzheimer disease vasculature: Journal of Neuropathology and Experimental Neurology. Decreased neprilysin immunoreactivity in Alzheimer disease, but not in pathological aging. Structure, evolutionary conservation, and functions of angiotensin- and endothelin-converting enzymes.

    International Review of Cytology. Trends in Pharmacological Sciences. Molecular pharmacology of endothelin converting enzymes. Human endothelin converting enzyme-2 ECE2: Biochimica et Biophysica Acta. Emoto N, Yanagisawa M. Endothelin-converting enzyme-2 is a membrane-bound, phosphoramidon-sensitive metalloprotease with acidic pH optimum. Cloning and functional expression of human endothelin-converting enzyme cDNA. Journal of Cardiovascular Pharmacology. Cellular distribution of endothelin converting enzyme-1 in human tissues.

    The Journal of Histochemistry and Cytochemistry. Localization of endothelin-converting enzyme-1 in human kidney. The American Journal of Physiology. Localization and biochemical characterization of endothelinconverting enzyme. Immunolocalisation of endothelin-1 in human brain. Journal of Chemical Neuroanatomy. Endothelinconverting enzyme-1 is expressed in human cerebral cortex and protects against Alzheimer's disease.

    A fourth isoform of endothelin-converting enzyme ECE-1 is generated from an additional promoter molecular cloning and characterization. European Journal of Biochemistry. Identification and characterization of two isoforms of an endothelinconverting enzyme Human endothelin-converting enzyme ECE The N-terminal segment of endothelin-converting enzyme ECE -1b contains a di-leucine motif that can redirect neprilysin to an intracellular compartment in Madin-Darby canine kidney MDCK cells. Recombinant human endothelin-converting enzyme ECE-1b is located in an intracellular compartment when expressed in polarized Madin-Darby canine kidney cells.

    Inhibitor potencies and substrate preference for endothelin-converting enzyme-1 are dramatically affected by pH. Alzheimer's disease beta-amyloid peptide is increased in mice deficient in endothelin-converting enzyme. Initial site of insulin cleavage by insulin protease. Substrate activation of insulin-degrading enzyme insulysin. A potential target for drug development. Human insulin-degrading enzyme shares structural and functional homologies with E.

    β-Amyloid Degradation and Alzheimer's Disease

    Localization of the gene encoding insulindegrading enzyme to human chromosome 10, bands q23—q Cytogenetics and Cell Genetics. Clearing the brain's amyloid cobwebs. Clinical and Investigative Medicine. Persinogen excretion uropepsin as an index of the influence of various life situations on gastric secretion. Trends in Biochemical Sciences. Insulin acts intracellularly on proteasomes through insulin-degrading enzyme. Overexpression of insulin degrading enzyme: Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulindegrading enzyme.

    Degradation of soluble amyloid beta-peptides , , and the Dutch variant Q by insulin degrading enzyme from Alzheimer disease and control brains. Degradation of amyloid beta-protein by ametalloprotease secreted by microglia and other neural and non-neural cells. Differential effects of proteases involved in intracellular degradation of amyloid beta-protein between detergent-soluble and -insoluble pools in CHO cells. Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo.


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    Partial loss-offunction mutations in insulin-degrading enzyme that induce diabetes also impair degradation of amyloid beta-protein. The American Journal of Pathology. Insulin-degrading enzyme in the Alzheimer's disease brain: Reduced hippocampal insulin-degrading enzyme in late-onset Alzheimer's disease is associated with the apolipoprotein E-epsilon4 allele. Membrane-associated zinc peptidase families: Molecular cloning of human testicular angiotensin-converting enzyme: The two homologous domains of human angiotensin I-converting enzyme are both catalytically active.

    Journal of Clinical Investigation. Saavedra JM, Chevillard C. Angiotensin-converting enzyme is present in the subfornical organ and other circumventricular organs of the rat. The brain renin-angiotensin system: Association between angiotensin-converting enzyme and Alzheimer disease. Alzheimer disease risk and genetic variation in ACE: Large meta-analysis establishes the ACE insertion-deletion polymorphism as a marker of Alzheimer's disease. American Journal of Epidemiology. Association between angiotensin-converting enzyme gene polymorphism and Alzheimer's disease in a Chinese population.

    Dementia and Geriatric Cognitive Disorders. The ACE gene and Alzheimer's disease susceptibility. Journal of Medical Genetics. Angiotensin converting enzyme and memory: International Journal of Neurology. The angiotensin-converting enzyme gene family: Angiotensin converting enzyme density is increased in temporal cortex from patients with Alzheimer's disease.

    European Journal of Pharmacology. Cortical alterations of angiotensin converting enzyme, angiotensin II and AT1 receptor in Alzheimer's dementia. Angiotensin converting enzyme in Alzheimer's disease increased activity in caudate nucleus and cortical areas. ECM and cell surface proteolysis: Progress in Cardiovascular Diseases. Extracellular proteases in neuronal function and degeneration. Neuronal cell death and tPA. Emotions are building up in the field of extracellular proteolysis. Trends in Molecular Medicine. In vitro stimulation of tissue-type plasminogen activator by Alzheimer amyloid beta-peptide analogues.

    Amyloid beta peptides stimulate tissue-type plasminogen activator but not recombinant prourokinase. Brain plasmin enhances APP alphacleavage and Abeta degradation and is reduced in Alzheimer's disease brains. Tissue plasminogen activator requires plasminogen to modulate amyloid-beta neurotoxicity and deposition. Raft disorganization leads to reduced plasmin activity in Alzheimer's disease brains. Urokinase-type plasminogen activator inhibits amyloid-beta neurotoxicity and fibrillogenesis via plasminogen. Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis.

    Plasmin deficiency does not alter endogenous murine amyloid beta levels in mice. Possible increased risk for Alzheimer's disease associated with neprilysin gene. Journal of Neural Transmission. Polymorphisms in neprilysin gene affect the risk of Alzheimer's disease in Finnish patients. Journal of Neurology, Neurosurgery, and Psychiatry. Association of the Neprilysin gene with susceptibility to late-onset Alzheimer's disease.

    β-Amyloid Degradation and Alzheimer's Disease

    Association between angiotensin-converting enzyme gene and late onset Alzheimer's disease in Han Chinese. Insulin-degrading enzyme and Alzheimer disease: Mutation screening and association study of the neprilysin gene in sporadic Alzheimer's disease in Chinese persons. The Journals of Gerontology. ACE gene is associated with Alzheimer's disease and atrophy of hippocampus and amygdala. Insulin-degrading enzyme degrades amyloid peptides associated with British and Danish familial dementia. No association between polymorphisms in the neprilysin promoter region and Swedish Alzheimer's disease patients.

    No association between the insulin degrading enzyme gene and Alzheimer's disease in a Japanese population. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. Association studies between risk for late-onset Alzheimer's disease and variants in insulin degrading enzyme. Lack of association between angiotensin converting enzyme polymorphism and sporadic Alzheimer's disease. Polymorphisms of insulin degrading enzyme gene are not associated with Alzheimer's disease. Lack of association of neprilysin polymorphism with Alzheimer's disease and Alzheimer's diseasetype neuropathological changes.

    Oxidative damage in Alzheimer's. Oxidative stress and neuronal adaptation in Alzheimer disease: Oxidative posttranslational modifications in Alzheimer disease. A possible pathogenic role in the formation of senile plaques and neurofibrillary tangles.