J Neurosci. Nat Genet. Neurochem Int. Neurobiol Aging. Embo J. Nat Neurosci. Ho A, Sudhof TC: Binding of F-spondin to amyloid-beta precursor protein: a candidate amyloid-beta precursor protein ligand that modulates amyloid-beta precursor protein cleavage. Cell Death Differ. Yamazaki T, Koo EH, Selkoe DJ: Cell surface amyloid beta-protein precursor colocalizes with beta 1 integrins at substrate contact sites in neural cells.
Mol Cell. J Biol Chem. Aging Cell. Nat Med. Sisodia SS: Beta-amyloid precursor protein cleavage by a membrane-bound protease. Ann N Y Acad Sci. J Neurochem. Mattson MP: Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol Rev. Merlos-Suarez A, Ruiz-Paz S, Baselga J, Arribas J: Metalloprotease-dependent protransforming growth factor-alpha ectodomain shedding in the absence of tumor necrosis factor-alpha-converting enzyme.
Biochem J. Mol Med. Eur J Neurosci. Faseb J. Mol Cell Neurosci. The Alzheimer's disease beta-secretase. PubMed Google Scholar. Neurobiol Dis. Biochem Soc Trans. Cytogenet Cell Genet. Biol Chem. EMBO Rep. Kim J, Schekman R: The ins and outs of presenilin 1 membrane topology. Google Scholar. Dev Cell. Nat Cell Biol. J Cell Biol. J Cell Sci. Tamayev R, Zhou D, D'Adamio L: The interactome of the amyloid beta precursor protein family members is shaped by phosphorylation of their intracellular domains.
Bredesen DE: Neurodegeneration in Alzheimer's disease: caspases and synaptic element interdependence. Jarrett JT, Berger EP, Lansbury PT: The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease. Am J Pathol. Arch Pathol Lab Med. Biol Psychiatry. J Alzheimers Dis.
King GD, Scott Turner R: Adaptor protein interactions: modulators of amyloid precursor protein metabolism and Alzheimer's disease risk?. Exp Neurol. Brain Res Rev. Mol Cell Biol. Int J Biochem Cell Biol. Sorkin A: Cargo recognition during clathrin-mediated endocytosis: a team effort. Curr Opin Cell Biol. Chyung JH, Selkoe DJ: Inhibition of receptor-mediated endocytosis demonstrates generation of amyloid beta-protein at the cell surface.
BMC Cell Biol. Hum Mol Genet. Arch Neurol. Narita M, Holtzman DM, Schwartz AL, Bu G: Alpha2-macroglobulin complexes with and mediates the endocytosis of beta-amyloid peptide via cell surface low-density lipoprotein receptor-related protein.
Evidence that LRP contributes to the pathogenesis of Alzheimer's disease. Mattson MP: Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol Rev. Epub Oct Koo EH, et al: Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport.
J Cell Biol. Lyckman AW, et al: Post-translational processing and turnover kinetics of presynaptically targeted amyloid precursor superfamily proteins in the central nervous system. Moya KL, et al: The amyloid precursor protein is developmentally regulated and correlated with synaptogenesis.
Dev Biol. Hung AY, et al: Increased expression of beta-amyloid precursor protein during neuronal differentiation is not accompanied by secretory cleavage. Bibel M, et al: Differentiation of mouse embryonic stem cells into a defined neuronal lineage. Murakami N, et al: Experimental brain injury induces expression of amyloid precursor protein, which may be related to neuronal loss in the hippocampus.
J Neurotrauma. Van den Heuvel C, et al: Upregulation of amyloid precursor protein messenger RNA in response to traumatic brain injury: an ovine head impact model. Exp Neurol. Leyssen M, et al: Amyloid precursor protein promotes post-developmental neurite arborization in the Drosophila brain.
Epub Jul Rossjohn J, et al: Crystal structure of the N-terminal, growth factor-like domain of Alzheimer amyloid precursor protein. Nat Struct Biol. Saitoh T, et al: Secreted form of amyloid beta protein precursor is involved in the growth regulation of fibroblasts. Meziane H, et al: Memory-enhancing effects of secreted forms of the beta-amyloid precursor protein in normal and amnestic mice. Thornton E, et al: Soluble amyloid precursor protein alpha reduces neuronal injury and improves functional outcome following diffuse traumatic brain injury in rats.
Copanaki E, et al: sAPPalpha antagonizes dendritic degeneration and neuron death triggered by proteasomal stress. Mol Cell Neurosci. Allinquant B, et al: Downregulation of amyloid precursor protein inhibits neurite outgrowth in vitro. Perez RG, et al: The beta-amyloid precursor protein of Alzheimer's disease enhances neuron viability and modulates neuronal polarity. Herard AS, et al: siRNA targeted against amyloid precursor protein impairs synaptic activity in vivo.
Taylor CJ, et al: Endogenous secreted amyloid precursor protein-alpha regulates hippocampal NMDA receptor function, long-term potentiation and spatial memory. Neurobiol Dis. Han P, et al: Suppression of cyclin-dependent kinase 5 activation by amyloid precursor protein: a novel excitoprotective mechanism involving modulation of tau phosphorylation. Caille I, et al: Soluble form of amyloid precursor protein regulates proliferation of progenitors in the adult subventricular zone.
Epub Apr 8. Gakhar-Koppole N, et al: Activity requires soluble amyloid precursor protein alpha to promote neurite outgrowth in neural stem cell-derived neurons via activation of the MAPK pathway. Eur J Neurosci. Stem Cells. Naumann N, et al: Transgenic expression of human wild-type amyloid precursor protein decreases neurogenesis in the adult hippocampus. Schwarzman AL, et al: Transthyretin sequesters amyloid beta protein and prevents amyloid formation.
Journal of Neuroscience. Buxbaum JN, et al: Transthyretin protects Alzheimer's mice from the behavioral and biochemical effects of Abeta toxicity. Kuro-o M, et al: Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Kurosu H, et al: Suppression of aging in mice by the hormone Klotho. Imura A, et al: alpha-Klotho as a regulator of calcium homeostasis. Lannfelt L, et al: Amyloid beta-peptide in cerebrospinal fluid in individuals with the Swedish Alzheimer amyloid precursor protein mutation.
Neurosci Lett. Sennvik K, et al: Levels of alpha- and beta-secretase cleaved amyloid precursor protein in the cerebrospinal fluid of Alzheimer's disease patients. Mol Med. Tyler SJ, et al: alpha- and beta-secretase: profound changes in Alzheimer's disease. Roe CM, et al: Cancer linked to Alzheimer disease but not vascular dementia. Venkataramani V, et al: Histone deacetylase inhibitor valproic acid inhibits cancer cell proliferation via down-regulation of the alzheimer amyloid precursor protein.
Turner PR, et al: Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Prog Neurobiol. Suzuki T, Nakaya T: Regulation of amyloid beta-protein precursor by phosphorylation and protein interactions. Iijima K, et al: Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by cyclin-dependent kinase 5. Kimberly WT, et al: Physiological regulation of the beta-amyloid precursor protein signaling domain by c-Jun N-terminal kinase JNK3 during neuronal differentiation.
Muresan Z, Muresan V: c-Jun NH2-terminal kinase-interacting protein-3 facilitates phosphorylation and controls localization of amyloid-beta precursor protein. Ando K, et al: Role of phosphorylation of Alzheimer's amyloid precursor protein during neuronal differentiation. Muresan Z, Muresan V: Coordinated transport of phosphorylated amyloid-beta precursor protein and c-Jun NH2-terminal kinase-interacting protein Ando K, et al: Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of beta-amyloid.
Tamayev R, Zhou D, D'Adamio L: The interactome of the amyloid beta precursor protein family members is shaped by phosphorylation of their intracellular domains. Mol Neurodegener. Pastorino L, et al: The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production. Lu PJ, et al: The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein.
Sano Y, et al: Physiological mouse brain Abeta levels are not related to the phosphorylation state of threonine of Alzheimer's APP.
Pietrzik CU, et al: FE65 constitutes the functional link between the low-density lipoprotein receptor-related protein and the amyloid precursor protein.
Yankner BA, et al: Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease. Oster-Granite ML, et al: Age-dependent neuronal and synaptic degeneration in mice transgenic for the C terminus of the amyloid precursor protein. Cupers P, et al: The amyloid precursor protein APP -cytoplasmic fragment generated by gamma-secretase is rapidly degraded but distributes partially in a nuclear fraction of neurones in culture.
Kimberly WT, et al: The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner. Passer B, et al: Generation of an apoptotic intracellular peptide by gamma-secretase cleavage of Alzheimer's amyloid beta protein precursor. Kinoshita A, et al: The gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein induces apoptosis via Tip60 in H4 cells.
BMB Rep. Gao Y, Pimplikar SW: The gamma-secretase-cleaved C-terminal fragment of amyloid precursor protein mediates signaling to the nucleus. Ghosal K, et al: Alzheimer's disease-like pathological features in transgenic mice expressing the APP intracellular domain. Lu DC, et al: A second cytotoxic proteolytic peptide derived from amyloid beta-protein precursor. Nat Med. Bertrand E, et al: A short cytoplasmic domain of the amyloid precursor protein induces apoptosis in vitro and in vivo.
Epub Apr Park SA, et al: Mechanism of cytotoxicity mediated by the C31 fragment of the amyloid precursor protein. Harris JA, et al: Many neuronal and behavioral impairments in transgenic mouse models of Alzheimer's disease are independent of caspase cleavage of the amyloid precursor protein. De Strooper B, Annaert W: Novel research horizons for presenilins and gamma-secretases in cell biology and disease.
Annu Rev Cell Dev Biol. Goodger ZV, et al: Nuclear signaling by the APP intracellular domain occurs predominantly through the amyloidogenic processing pathway. Sala Frigerio C, et al: beta-Secretase cleavage is not required for generation of the intracellular C-terminal domain of the amyloid precursor family of proteins. FEBS J. Cao X, Sudhof TC: Dissection of amyloid-beta precursor protein-dependent transcriptional transactivation. Epub Mar Epub Aug Epub Dec 6.
Giliberto L, et al: Evidence that the Amyloid beta Precursor Protein-intracellular domain lowers the stress threshold of neurons and has a "regulated" transcriptional role. Kim HS, et al: C-terminal fragments of amyloid precursor protein exert neurotoxicity by inducing glycogen synthase kinase-3beta expression. Epub Jun 7. Current Alzheimer Research. Muller T, et al: Modulation of gene expression and cytoskeletal dynamics by the amyloid precursor protein intracellular domain AICD.
Mol Biol Cell. Hebert SS, et al: Regulated intramembrane proteolysis of amyloid precursor protein and regulation of expression of putative target genes.
Epub May Repetto E, et al: Presenilin 1 regulates epidermal growth factor receptor turnover and signaling in the endosomal-lysosomal pathway. Journal of Biological Chemistry. Tamboli IY, et al: Loss of gamma-secretase function impairs endocytosis of lipoprotein particles and membrane cholesterol homeostasis.
Waldron E, et al: Increased AICD generation does not result in increased nuclear translocation or activation of target gene transcription. Exp Cell Res. Hornsten A, et al: APL-1, a Caenorhabditis elegans protein related to the human beta-amyloid precursor protein, is essential for viability. Epub Jan Li H, et al: Genetic dissection of the amyloid precursor protein in developmental function and amyloid pathogenesis. Gunawardena S, Goldstein LS: Disruption of axonal transport and neuronal viability by amyloid precursor protein mutations in Drosophila.
Curr Biol. Kamal A, et al: Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Aging Cell. Satpute-Krishnan P, et al: A peptide zipcode sufficient for anterograde transport within amyloid precursor protein. Lazarov O, et al: Axonal transport, amyloid precursor protein, kinesin-1, and the processing apparatus: revisited. Fossgreen A, et al: Transgenic Drosophila expressing human amyloid precursor protein show gamma-secretase activity and a blistered-wing phenotype.
Muller U, et al: Behavioral and anatomical deficits in mice homozygous for a modified beta-amyloid precursor protein gene. Zheng H, et al: beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Li ZW, et al: Generation of mice with a kb amyloid precursor protein gene deletion by Cre recombinase-mediated site-specific recombination in embryonic stem cells.
Ring S, et al: The secreted beta-amyloid precursor protein ectodomain APPs alpha is sufficient to rescue the anatomical, behavioral, and electrophysiological abnormalities of APP-deficient mice. Magara F, et al: Genetic background changes the pattern of forebrain commissure defects in transgenic mice underexpressing the beta-amyloid-precursor protein.
Steinbach JP, et al: Hypersensitivity to seizures in beta-amyloid precursor protein deficient mice. Cell Death Differ. Phinney AL, et al: No hippocampal neuron or synaptic bouton loss in learning-impaired aged beta-amyloid precursor protein-null mice. Priller C, et al: Synapse formation and function is modulated by the amyloid precursor protein.
Bittner T, et al: Gamma-secretase inhibition reduces spine density in vivo via an amyloid precursor protein-dependent pathway. Lee KJ, et al: Beta amyloid-independent role of amyloid precursor protein in generation and maintenance of dendritic spines.
Dawson GR, et al: Age-related cognitive deficits, impaired long-term potentiation and reduction in synaptic marker density in mice lacking the beta-amyloid precursor protein.
Seabrook GR, et al: Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein. Yang L, et al: Amyloid precursor protein regulates Cav1. Santos SF, et al: Expression of human amyloid precursor protein in rat cortical neurons inhibits calcium oscillations.
Yang L, et al: Increased asynchronous release and aberrant calcium channel activation in amyloid precursor protein deficient neuromuscular synapses.
Heber S, et al: Mice with combined gene knock-outs reveal essential and partially redundant functions of amyloid precursor protein family members. Wang B, et al: Amyolid precursor protein mediates presynaptic localization and activity of the high-affinity choline transporter.
Herms J, et al: Cortical dysplasia resembling human type 2 lissencephaly in mice lacking all three APP family members. Guenette S, et al: Essential roles for the FE65 amyloid precursor protein-interacting proteins in brain development.
Mech Dev. Barbagallo AP, et al: A single tyrosine residue in the amyloid precursor protein intracellular domain is essential for developmental function. Download references. You can also search for this author in PubMed Google Scholar. Correspondence to Hui Zheng. HZ and EHK wrote the manuscript. Structure and functions of the human amyloid precursor protein: the whole is more than the sum of its parts. Greeve, I.
Age-dependent neurodegeneration and Alzheimer-amyloid plaque formation in transgenic Drosophila. Groth, C. Pharmacological analysis of Drosophila melanogaster gamma-secretase with respect to differential proteolysis of Notch and APP. Guo, Q. APP physiological and pathophysiological functions: insights from animal models. Cell Res. Haass, C. Trafficking and proteolytic processing of APP. Hare, J. Protease inhibitors divert amyloid precursor protein to the secretory pathway.
Hayashi, J. Insect olfactory neurons in vitro : morphological and physiological characterization of cells from the developing antennal lobes of Manduca sexta. Calcium and potassium currents in leg motoneurons during postembryonic development in the hawkmoth Manduca sexta.
Hiruma, K. Horgan, A. G protein-mediated inhibition of neuronal migration requires calcium influx. A developmental role for the heterotrimeric G protein Go alpha in a migratory population of embryonic neurons. Hutagalung, A. Role of Rab GTPases in membrane traffic and cell physiology. Jung, C. Role of APP for dendritic spine formation and stability. Brain Res. Kamal, A. Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP.
Nature , — Khanna, M. Transcriptomic analysis of drosophila mushroom body neurons lacking amyloid-beta precursor-like protein activity.
Alzheimers Dis. Kimberly, W. The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner. Physiological regulation of the beta-amyloid precursor protein signaling domain by c-Jun N-terminal kinase JNK3 during neuronal differentiation. Kins, S. Subcellular trafficking of the amyloid precursor protein gene family and its pathogenic role in Alzheimer's disease.
Kogel, D. Roles of amyloid precursor protein family members in neuroprotection, stress signaling and aging. Koles, K. Mechanism of evenness interrupted Evi -exosome release at synaptic boutons. Koo, E. Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. Kraft, R. The steroid hormone hydroxyecdysone enhances neurite growth of Drosophila mushroom body neurons isolated during metamorphosis.
Kuijper, S. Regulation of angiogenesis by Eph-ephrin interactions. Trends Cardiovasc. Lan, Q. Lavore, A. Comparative analysis of zygotic developmental genes in Rhodnius prolixus genome shows conserved features on the tracheal developmental pathway. Insect Biochem.
Leyssen, M. Amyloid precursor protein promotes post-developmental neurite arborization in the Drosophila brain. Luo, D. Luo, L. Human amyloid precursor protein ameliorates behavioral deficit of flies deleted for Appl gene. Neuron 9, — Identification, secretion, and neural expression of APPL, a Drosophila protein similar to human amyloid protein precursor.
Lyckman, A. Post-translational processing and turnover kinetics of presynaptically targeted amyloid precursor superfamily proteins in the central nervous system.
Meyer, M. Immunological probes reveal spatial and developmental diversity in insect neuroglia. Milosch, N. Cell Death Dis. Muresan, V. Amyloid-beta precursor protein: multiple fragments, numerous transport routes and mechanisms.
The cleavage products of amyloid-beta precursor protein are sorted to distinct carrier vesicles that are independently transported within neurites. Nalivaeva, N. The amyloid precursor protein: a biochemical enigma in brain development, function and disease. FEBS Lett. Nhan, H. The multifaceted nature of amyloid precursor protein and its proteolytic fragments: friends and foes.
Acta Neuropathol. Nicolas, M. Amyloid precursor protein and neural development. Niederst, E. Axonal amyloid precursor protein and its fragments undergo somatodendritic endocytosis and processing. Cell 26, — Niikura, T. Nikolaev, A. APP binds DR6 to trigger axon pruning and neuron death via distinct caspases.
Nishimoto, I. Alzheimer amyloid protein precursor complexes with brain GTP-binding protein Go. Nature , 75— Octave, J. From synaptic spines to nuclear signaling: nuclear and synaptic actions of the amyloid precursor protein. Okamoto, T. Intrinsic signaling function of APP as a novel target of three V mutations linked to familial Alzheimer's disease. Embo J. Oland, L. Glial cells in the developing and adult olfactory lobe of the moth Manduca sexta. Cell Tissue Res.
Olsen, O. Genetic analysis reveals that amyloid precursor protein and death receptor 6 function in the same pathway to control axonal pruning independent of beta-secretase. Osterfield, M. Interaction of amyloid precursor protein with contactins and NgCAM in the retinotectal system. Pace, R. Evidence for the plasticity of arthropod signal transduction pathways.
Genes Evol. Papoulas, O. The golgin Lava lamp mediates dynein-based Golgi movements during Drosophila cellularization. Pardossi-Piquard, R. The physiology of the beta-amyloid precursor protein intracellular domain AICD. Patel, K. Autophagy proteins control goblet cell function by potentiating reactive oxygen species production. Perez, R. Mutagenesis identifies new signals for beta-amyloid precursor protein endocytosis, turnover, and the generation of secreted fragments, including Abeta Poeck, B.
Analysis of amyloid precursor protein function in Drosophila melanogaster. Prussing, K. Drosophila melanogaster as a model organism for Alzheimer's disease. Rama, N. Amyloid precursor protein regulates netrinmediated commissural axon outgrowth.
Ramabhadran, T. Proteolytic processing of human amyloid beta protein precursor in insect cells. Major carboxyl-terminal fragment is identical to its human counterpart. Ramaker, J. Amyloid precursor proteins interact with the heterotrimeric G protein Go in the control of neuronal migration. Manduca contactin regulates amyloid precursor protein-dependent neuronal migration. Ready, D. Development of the Drosophila retina, a neurocrystalline lattice.
Rice, H. Pancortins interact with amyloid precursor protein and modulate cortical cell migration. Systematic evaluation of candidate ligands regulating ectodomain shedding of amyloid precursor protein. Biochemistry 52, — Rodahl, L. Sabo, S. The amyloid precursor protein and its regulatory protein, FE65, in growth cones and synapses in vitro and in vivo. Sanchez-Wandelmer, J. Amphisomes: out of the autophagosome shadow? Satoh, A. Rab11 mediates post-Golgi trafficking of rhodopsin to the photosensitive apical membrane of Drosophila photoreceptors.
Schubert, W. Localization of Alzheimer beta A4 amyloid precursor protein at central and peripheral synaptic sites. Seals, D. The ADAMs family of metalloproteases: multidomain proteins with multiple functions. Genes Dev. Seamster, P. Quantitative measurements and modeling of cargo-motor interactions during fast transport in the living axon. Shaked, G. Interactions between the amyloid precursor protein C-terminal domain and G proteins mediate calcium dysregulation and amyloid beta toxicity in Alzheimer's disease.
FEBS J. Shariati, S. Redundancy and divergence in the amyloid precursor protein family. Simons, M. Intracellular routing of human amyloid protein precursor: axonal delivery followed by transport to the dendrites. Sinha, S. Purification and cloning of amyloid precursor protein beta-secretase from human brain. Sisodia, S. Beta-amyloid precursor protein cleavage by a membrane-bound protease.
Sola Vigo, F. Amyloid-beta precursor protein mediates neuronal toxicity of amyloid beta through Go protein activation. Aging 30, — Soldano, A. The Drosophila homologue of the amyloid precursor protein is a conserved modulator of Wnt PCP signaling.
PLoS Biol. Sosa, L. Amyloid precursor protein is an autonomous growth cone adhesion molecule engaged in contact guidance. Spradling, A. Transposition of cloned P elements into Drosophila germ line chromosomes. Stenmark, H. Rab GTPases as coordinators of vesicle traffic. Swanson, T. The insect homologue of the amyloid precursor protein interacts with the heterotrimeric G protein Go alpha in an identified population of migratory neurons. Szatmari, Z. Rab11 facilitates cross-talk between autophagy and endosomal pathway through regulation of Hook localization.
Cell 25, — Szodorai, A. Szpankowski, L. Subpixel colocalization reveals amyloid precursor protein-dependent kinesin-1 and dynein association with axonal vesicles. Tam, J. Tomlinson, A. Neuronal differentiation in Drosophila ommatidium. Torroja, L. The Drosophila beta-amyloid precursor protein homolog promotes synapse differentiation at the neuromuscular junction. Tschape, J.
The neurodegeneration mutant lochrig interferes with cholesterol homeostasis and Appl processing. Turner, P. Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Cellular functions of the amyloid precursor protein from development to dementia. Cell 32, — Villegas, C. Dual-tagged amyloid-beta precursor protein reveals distinct transport pathways of its N- and C-terminal fragments.
Wang, P. Wang, S. The retromer complex is required for rhodopsin recycling and its loss leads to photoreceptor degeneration. Weidemann, A. Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein.
Cell 57, — Wentzell, J. Alzheimer's disease and tauopathy studies in flies and worms. Amyloid precursor proteins are protective in Drosophila models of progressive neurodegeneration. Wright, J. Different isoforms of fasciclin II play distinct roles in the guidance of neuronal migration during insect embryogenesis.
A role for fasciclin II in the guidance of neuronal migration. Yamazaki, T.
0コメント