La chaîne invariante forme un complexe nonamérique avec les molécules classiques du CMH de classe II. HLA-DM et HLA-DO, des molécules non-classiques de classe II, sont aussi impliquées dans la présentation des peptides antigéniques aux lymphocytes T. Ces molécules chaperones de la présentation antigénique modulent la capacité d’une cellule à présenter des antigènes par les moloécules classiques du CMH de classe II. La régulation transcriptionnelle des molécules chaperones, tout comme celle des autres molécules du CMH de classe II, est assurée par le transactivateur CIITA. La molécule HLA-DR peut être régulée négativement de manière post-traductionnelle par ubiquitination grâce à l’enzyme E3 ubiquitine ligase MARCH1. Celle-ci est induite par l’interleukine-10 dans les monocytes. L’objectif de ce projet était de déterminer si l’ubiquitination par MARCH1 peut aussi réguler l’expression des molécules chaperones de la présentation antigénique. Les expériences furent réalisées dans le contexte de co-transfections en cellules HEK293T. L’expression des molécules fut évaluée par immunomarquages et cytométrie de flux. Il a été montré que l’isoforme p33 de la chaîne invariante est régulé négativement en présence de MARCH1 à partir de la surface cellulaire, causant ainsi sa dégradation. Tel que démontré par l’utilisation d’un mutant dépourvu de queue cytoplasmique, cette dernière région n’est pas indispensable à ce phénomène. Une hypothèse est qu’une molécule non-identifiée, associée à Ii, serait ubiquitinée par MARCH1, l’entraînant dans sa régulation négative. Il fut déterminer que cette molécule n’était pas CXCR2, un récepteur pouvant être impliqué, avec la chaîne invariante et CD44, en tant que récepteur de MIF (Macrophage Inhibitory Factor). Il fut aussi montré que HLA-DO peut être ciblé par MARCH1 mais ceci ne semble pas être un phénomène dominant; l’expression des complexes DO/DM n’étant pas affectée bien qu’ils entrent en interaction avec MARCH1. L’expression de HLA-DM n’est pas affectée par MARCH1. Il n’a toutefois pas été déterminé hors de tout doute si MARCH1 peut modifier DM; des résultats obtenus avec une queue cytoplasmique de DM possédant une lysine laissant suggérer qu’il est possible que MARCH1 interagisse avec DM. Dans l’ensemble, les travaux démontrent que l’ubiquitination par MARCH1 joue un rôle dans la régulation post-transcriptionnelle de la chaîne invariante p33 mais pas HLA-DO et HLA-DM. / The invariant chain, which form a nonameric complex with the classical MHC class II molecules. HLA-DM and HLA-DO (non-classical class II molecules) are involved in the presentation of antigens to T lymphocytes. The chaperons molecules of the antigenic presentation can modulate the capacity of the cells to present antigens. The transcriptional regulation of the chaperons and all of the other molecules linked to the MHC is assured by the CIITA transactivator. Little is know of the post-transcriptional mechanisms, other than the fact that HLA-DR molecule can be down-regulated by ubiquitination due to E3 ubiquitin ligase MARCH1. MARCH1 is induce by interleukin-10 in monocytes. The goal of this project is to figure out if ubiquitination by MARCH1 can also regulate the expression of the antigenic presentation chaperons. The experiences were performed in the context of co-transfections in HEK293T cells and the expression of the diverses molecules was evaluated by cell stainings and FACS analysis. The p33 isoform of the invariant chain was found to be down-regulated and degraded in the presence of MARCH1. The invariant chain cytoplasmic tail is not completely essential to this phenomenon; a non-identified molecule, associated with Ii, is probably ubiquitinated by MARCH1 and is then down-regulated, together with Ii. It was shown tha CXCR2, a reeptor involved with the invariant chain and CD44 in the reception of the MIF signal, is not that molecule. HLA-DO can ben targetd by MARCH1 but this does not seem to be a general phenomenon; the expression of the DO/DM complexes remaning unaffected even with the interaction of those complexes with MARCH1. Therefore, a certain protection seem to be provided by HLA-DM to HLA-DO. The expression of HLA-DM itself is not affected by the presence of MARCH1. However, it was not cleary demonstrated if MARCH1 can modify DM. Some results obtained with a cytoplasmic tail of DM comprising an additional lysine suggest that there is a possibility that MARCH1 interact with DM. Generally, the work presented here show that ubiquitination by MARCH1 is involved in post-transcriptionnal regulation of the p33 isoform of the invariant chain but not in the regulation of HLA-DO and HLA-DM.

The Hall resistivity in ferromagnetic materials has an anomalous contribution proportional to the magnetization, which is defined as the anomalous Hall effect (AHE). Being a central topic in the study of ferromagnetic materials for many decades, the AHE was revived in recent years by generating many new understandings and phenomena, e.g. spin-Hall effect, topological insulators. The phase diagram of the AHE was shown recently to exhibit three distinct regions: a skew scattering region in the high conductivity regime, a scattering-independent normal metal regime, and an insulating regime. While the origin of the metallic regime scaling has been understood for many decades through the expected dependence of each contribution, the origin of the surprising scaling in the insulating regime was completely unexplained, leaving the primary challenge to the last step to understand fully the AHE. In this dissertation work we developed a theory to study the AHE in the disordered insulating regime, whose scaling relation is observed to be omega_xy^AH is proportional to omega_xx^(1.40∼1.75) in a large range of materials. This scaling is qualitatively different from the ones observed in metals. In the metallic regime where kFl > > 1, the linear response theory predicts that omega_xx is proportional to the quasi-particle lifetime tau, while omega_xy^AH scales as alpha*tau beta*tau^0, indicating that the upper limit of the scaling exponent is 1.0. Basing our theory on the phonon-assisted hopping mechanism and percolation theory, we derived a general formula for the anomalous Hall conductivity (AHC), and showed that the AHC scales with the longitudinal conductivity as omega_xy^AH ~ omega_xx^gamma with gamma predicted to be 1.33 <= gamma <= 1.76, quantitatively in agreement with the experimental observations. This scaling remains similar regardless of whether the hopping process is long range type (varible range hopping) or short range type (activation E3 hopping), or is influenced by interactions, i.e. Efros-Shklovskii (E-S) regime. Our theory completes the understanding of the AHE phase diagram in the insulating regime.

Organic solar cells have great potential for cost-effective and large area electricity production, but their applicability is limited by the relatively low efficiency. In this dissertation I report investigations of novel materials and the underlying principles of organic solar cells, carried out at the University of St Andrews between 2011 and 2015. Key results of this investigation: • The charge carrier mobility of organic semiconductors in the active layer of polymer solar cells has a rather small influence on the power conversion efficiency. Cooling solar cells of the polymer:fullerene blend PTB7:PC₇₁BM from room temperature to 77 K decreased the hole mobility by a factor of thousand but the device efficiency only halved. • Subphthalocyanine molecules, which are commonly used as electron donor materials in vacuum-deposited active layers of organic solar cells, can, by a slight structural modification, also be used as efficient electron acceptor materials in solution-deposited active layers. Additionally these acceptors offer, compared to standard fullerene acceptors,advantages of a stronger light absorption at the peak of the solar spectrum. • A low band-gap polymer donor material requires a careful selection of the acceptor material in order to achieve efficient charge separation and a maximum open circuit voltage. • Metal structures in nanometer-size can efficiently enhance the electric field and light absorption in organic semiconductors by plasmonic resonance. The fluorescence of a P3HT polymer film above silver nanowires, separated by PEDOT:PSS, increased by factor of two. This could be clearly assigned to an enhanced absorption as the radiative transition of P3HT was identical beside the nanowires. • The use of a processing additive in the casting solution for the active layer of organic solar cells of PTB7:PC₇₁BM strongly influences the morphology, which leads not only to an optimum of charge separation but also to optimal charge collection.

No description available.

[ES] El crecimiento de las plantas se ve afectado por el estrés abiótico, sequía, salinidad o altas temperaturas. La transducción de señales de estrés abiótico es fundamental para generar una respuesta fisiológica adecuada, que implica la participación de diferentes hormonas vegetales, siendo el ácido abscísico (ABA) el regulador hormonal crítico en la regulación de la respuesta de la planta a situaciones de estrés por déficit hídrico. La vía de señalización de ABA y los componentes principales están bien caracterizados molecular y bioquímicamente. Los receptores de ABA "Pyrabactin Resistance 1"(PYR)/"PYR1-LIKE" (PYL)/ "Regulatory Component of ABA Receptor" (RCAR) juegan un papel importante en la regulación cuantitativa de la señalización ABA tanto en semillas como en tejidos vegetativos. Aunque la función bioquímica de los receptores PYR/PYL/RCARs de ABA, está bien caracterizada, se conoce poco sobre otros aspectos con relevancia biológica, como sus modificaciones postraduccionales o la regulación de su vida media. Uno de los avances recientes en este campo ha sido el descubrimiento de una nueva familia de E3 ligasas llamadas RSL1/RFAs ("RING-finger-ABA-related") que consta de al menos 10 miembros, reguladores clave de la estabilidad de los receptores PYR/PYL/RCAR de ABA en tejidos de raíces y hojas, regulando su degradación en diferentes ubicaciones celulares. Un estudio detallado de esta familia génica reveló que RSL1/RFA se caracterizan estructuralmente por la presencia de tres dominios RING putativos en tándem, denominados "RING1-IN BETWEEN RING-RING2" (RBR), y en consecuencia pertenecen a la familia de E3 ligasas de tipo RBR. Cinco miembros de la familia RSL1/RFA, RSL1 y RFA6-RFA9, contienen un dominio TM en el extremo C-terminal, lo que sugiere que RFA6-RFA9 también se localizan en la membrana plasmática. Sin embargo, otros miembros de las E3 ligasas como RFA1-RFA5 carecen del dominio TM C-terminal y su caracterización funcional, así como su ubicación celular, aún no se conocen. Nosotros mostramos que la E3 ligasa RFA1 se localiza en núcleo y citosol, mientras que RFA4 muestra una localización específica en el núcleo promoviendo la degradación nuclear de los receptores ABA. Por lo tanto, los miembros de la familia RSL1/RFA interactúan con los receptores ABA en la membrana plasmática, el citosol y el núcleo, dirigiéndolos a su degradación a través de la vía endosomal/vacuolar (en el caso de RSL1) o el proteosoma 26S (para RFA1 y RFA4). Proporcionamos información sobre la función fisiológica de estas E3 ligasas de tipo RBR. Realizando tanto mutagénesis como ensayos bioquímicos para identificar la cisteína 361 (Cys361) en RFA4 como la Cys del sitio activo, que es una característica distintiva de las E3 ligasas de tipo RBR. Demostramos mediante análisis de inmunotransferencia del mutante con pérdida de función de rfa1rfa4 que los niveles endógenos de los receptores de ABA PYR1 y PYL4 aumentan en comparación con las plantas de tipo silvestre. Hemos identificado una enzima E2, "Ubiquitin Conjugating Enzyme 26" (UBC26), como la enzima nuclear canónica E2 que interactúa con la E3 ligasa RFA4 y forma complejos UBC26-RFA4-Receptor, formando agregados nucleares. Generamos alelos ubc26 con pérdida de función que mostraban una mayor sensibilidad a ABA y acumulación de receptores ABA en comparación con el tipo silvestre. En definitiva, hemos revelado un sofisticado sistema de ubiquitinación de receptores ABA en diferentes ubicaciones subcelulares llevado a cabo a través de la familia de E3 ligasas RSL1/RFA de tipo RBR. Por otro lado, hemos iniciado pruebas bioquímicas para identificar la S-acilación en el dominio TM de RSL1. Generando RSL1C334S, RSL1 C5S y RSL1C6S mediante mutagénesis y RSL1ΔTM que presenta una delección del dominio TM. Los estudios iniciales han demostrado que los residuos de Cys cercanos al dominio TM están S-acilados. Finalmente, generamos nu / [CA] El creixement de les plantes es pot veure afectat per l'estrès abiòtic, sequera, salinitat o altes temperatures. La transducció de senyals d'estrès abiòtic és fonamental per a generar una resposta fisiològica adequada, que implica la participació de diferents hormones vegetals, sent l'àcid abscísic (ABA) el regulador hormonal crític en la regulació de la resposta de la planta a situacions d'estrès per dèficit hídric. La ruta de senyalització d'ABA i els components principals de la ruta estan ben caracteritzats molecularment i bioquímica. Els receptors "Pyrabactin Resistance 1"(PYR)/"PYR1-LIKE"(PYL)/"Regulatory Component of ABA Receptor" (RCAR) exerceixen un paper important en la regulació quantitativa en resposta a l'estrès tant en llavors com en planta. Encara que la funció bioquímica dels receptors PYR/PYL/RCARs d'ABA, està ben caracteritzada en els últims anys, es coneix poc sobre altres aspectes amb rellevància biològica, com les seues modificacions postraduccionals o la regulació de la seua vida mitjana. Un dels avanços recents en aquest camp ha sigut el descobriment d'una nova família d'E3 ligases anomenades RSL1/RFAs ("RING-finger-ABA-related") que consta d'almenys 10 membres, que són reguladors clau de l'estabilitat dels receptors PYR/PYL/RCAR d'ABA en teixits d'arrels i fulles, regulant la seua degradació en diferents ubicacions cel·lulars. Un estudi més detallat d'aquesta família gènica va revelar que RSL1/RFAs es caracteritzen estructuralment per la presència de tres dominis RING putatius en tàndem, denominats "RING1-IN BETWEEN RING-RING2" (RBR), i en conseqüència pertanyen a la família d'E3 ligases de tipus RBR. Cinc membres de la família RSL1/RFA, RSL1 i RFA6-RFA9, contenen un domini TM en l'extrem C-terminal, la qual cosa suggereix que RFA6-RFA9 també es localitzen en la membrana plasmàtica. No obstant això, altres membres d'aquesta família d'E3 ligases com RFA1-RFA5 manquen del domini TM C-terminal i la seua caracterització funcional, així com la seua ubicació cel·lular, encara no ha sigut investigada. Vam mostrar que l'E3 ligasa RFA1 es localitza tant en el nucli com en el citosol, mentre que RFA4 mostra una localització específica en el nucli promovent la degradació nuclear dels receptors ABA. Per tant, els membres de la família RSL1/RFA interactuen amb els receptors ABA en la membrana plasmàtica, el citosol i el nucli, dirigint-los a la seua degradació a través de la vía endosomal/vacuolar (en el cas de RSL1) o el proteosoma 26S (per a RFA1 i RFA4). Proporcionem informació sobre la funció fisiològica d'aquestes E3 ligases de tipus RBR. Realitzant tant mutagènesis com a assajos bioquímics per a identificar la cisteïna 361 (Cys361) en RFA4 com la Cys del lloc actiu, que és una característica distintiva de les E3 ligases de tipus RBR. Hem demostrat mitjançant una anàlisi d'immuno-transferència del mutant amb pèrdua de funció de rfa1rfa4 que els nivells endògens dels receptors d'ABA PYR1 i PYL4 augmenten en comparació amb les plantes de tipus silvestre. D'altra banda, hem identificat un enzim E2, "Ubiquitin Conjugating Enzyme 26" (UBC26), com l'enzim nuclear canònic E2 que interactua amb l'E3 ligasa RFA4 i forma complexos UBC26-RFA4-Receptor, formant agregats nuclears. També generem al·lels ubc26 amb pèrdua de funció que mostraven una major sensibilitat a ABA i acumulació de receptors ABA en comparació amb el tipus silvestre. En definitiva, hem revelat un sofisticat sistema d'ubiquitinació de receptors ABA en diferents ubicacions subcel·lulars dut a terme a través de la família d'E3 ligases RSL1/RFA de tipus RBR. Hem iniciat proves bioquímiques per a identificar la S-acilació en el domini TM de RSL1. Hem generat RSL1C334S, RSL1 C5S i RSL1C6S mitjançant mutagènesis, així com RSL1ΔTM que presenta una delecció del domini TM. Els estudis inicials han demostrat que els residus de Cys pròxims al domini TM estan S-acilados. Final / [EN] Plant growth is affected by abiotic stress, drought, salinity or high temperature. Signal transduction of abiotic stress is crucial to generate an appropriated physiological response, which involves the participation of different plant hormones, being abscisic acid (ABA) the critical hormonal regulator in regulating the plant's response to situations of stress due to water deficit. The ABA signaling pathway and the major components of the pathway are well characterized molecularly and biochemically. Pyrabactin Resistance 1 (PYR)/PYR1-LIKE (PYL)/Regulatory Component of ABA Receptor (RCAR) ABA receptors play an important role in quantitative regulation of ABA signaling both in seeds and vegetative tissues. Although the biochemical function of the PYR/PYL/RCAR ABA receptors has been well established in recent years, little is known about other aspects with biological relevance, such as their post-translational modifications or the regulation of their half-life. One of the recent advances in this field has been the discovery of a new family of E3 ligases called RSL1/RFAs (RING-finger-ABA-related) that consists of at least 10 members, which are key regulators of the stability of PYR/PYL/RCARs in root and leaf tissues, and regulate the degradation of ABA receptors at different cellular locations. Further inspection of the gene family revealed that RSL1/RFAs are structurally characterized by the presence of three putative RING domains in tandem, named as RING1-IN BETWEEN RING (IBR)-RING2, and accordingly they belong to the RBR-type E3 ligase family. Five members of the RSL1/RFA family, that is, RSL1 and RFA6-RFA9, contain a TM domain at the C-terminal end of the proteins, which suggests that RFA6-RFA9 are also localized in plasma membrane. However, other members of this family of E3 ligases such as RFA1-RFA5 lack the C-terminal TM domain and their functional characterization, as well as their cellular location, has not been investigated yet. In this study we show that the E3 ligase RFA1 is localized both in the nucleus and in the cytosol, while RFA4 shows a specific localization in the nucleus promoting the nuclear degradation of ABA receptors. Therefore, we members of the RSL1/RFA family interact with ABA receptors at the plasma membrane, cytosol and nucleus, targeting them for degradation via the endosomal/vacuolar pathway (in the case of RSL1) or the 26S- proteasome (for RFA1 and RFA4). We provide information on the physiological function of these RBR-type E3 ligases, which are hardly explored in plants. Additionally, we performed mutagenesis and biochemical assays to identify Cys361 in RFA4 as the active site cysteine, which is a distinctive feature of RBR-type E3 ligases. We have shown by immunoblot analysis of the rfa1rfa4 loss-of-function mutant that endogenous levels of ABA receptors PYR1 and PYL4 are increased compared to wild-type plants. On the other hand, we have identified an E2 enzyme, Ubiquitin Conjugating Enzyme 26 (UBC26), as the canonical nuclear enzyme E2 that interacts with the E3 ligase RFA4 and forms UBC26-RFA4-Receptor complexes, forming nuclear aggregates. We also generated loss-of function ubc26 alleles that exhibited higher sensitivity to ABA and accumulation of ABA receptors compared to wild type. We have revealed a sophisticated ubiquitination system of ABA receptors in different subcellular locations carried out through the RBR-type RSL1/RFA family of E3 ligases. We have proceeded with the biochemical and genetic study of the different members of the family. We have started biochemical tests to identify the S-acylation in the TM domain of RSL1. To this end, we have generated RSL1C334S, RSL1 C5S and RSL1C6S by mutagenesis as well as RSL1ΔTM, a deletion of the TM domain. Initial studies have shown that Cys residues close to the TM domain are S-acylated. Finally, we have also generated new combined mutants: rsl1rfa1, rsl1rfa5, rfa1rfa5 and rsl1rfa1rfa5. / Fernández López, MA. (2021). Regulación de la señalización del ABA mediante mecanismos que controlan vida media y actividad de los receptores PYR/PYL [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/172364 / TESIS

No description available.

This thesis takes as its starting point the use of extracts from the works of historical authors who wrote in England in the early to mid twelfth-century. It focuses upon the ways in which their works began to be incorporated into three particular texts in the later twelfth and early thirteenth centuries. Through the medium of individual case studies – De Abbatibus (Abingdon), CCCC 139 (Durham) and The London Collection three elements are explored (i) how mediaeval writers used extracts from the works of others in ways which differed from modern practices with their concerns over charges of plagiarism and unoriginality (ii) how the structural and narrative roles which the use of extracts played within the presentation of these texts (iii) how the application of approaches developed in the twentieth century, which transformed how texts are now analysed, enabled a re-evaluation and re-interpretation of their use of source material with greater sensitivity to their original purposes This analysis casts fresh light upon the how and why these texts were produced and the means by which they fulfilled their purposes and reveals that despite their disparate origins and individual perspectives these three texts share two common features: (i) they follow a common three stage pattern of development (ii) they deal with similar issues: factional insecurities and concerns about the quality of those in power over them – using an historical perspective The analysis also reveals the range of techniques which were at the disposal of the composers of these texts, dispelling any notion that they were either unsophisticated or naïve in their handling of their source materials. Together these texts demonstrate how mediaeval authors used combinations of extracts as a means of responding quickly and flexibly to address particular concerns. Such texts were not regarded as being set in stone but rather as fluid entities which could be recombined at will in order to produce new works as required.

The ability of plants to sense and respond to environmental and endogenous signals is essential to their growth and development. As part of these diverse cellular functions, ubiquitin-mediated proteolysis has emerged to be an important process involved in how plant signalling pathways can be regulated in response to such cues. Of the three enzymes involved in linking ubiquitin to protein targets, E3 ubiquitin ligases are of interest as they confer substrate specificity during this ubiquitination process. The overall focal point of this research is on plant U-box (PUB) E3 ubiquitin ligases, a family that has undergone a large gene expansion possibly attributable to the regulation of biological processes unique to the plant life cycle. In Arabidopsis there are 64 predicted PUBs, many for which biological roles have yet to be determined. And as research continues to uncover PUB functions, the functional diversity in the gene family will likely expand. Specifically the focus of this research is on characterizing two ARM repeat-containing PUBs – AtPUB18 and AtPUB19. General analysis of pub18 and pub19 T-DNA insertion lines for growth defects did not yield distinct altered phenotypes. Closer inspection of selected lines showed independent gene assortment phenotypes that, with further inordinately convoluted pursuit, proved to have an AtPUB18/19-unrelated outcome. The availability of Arabidopsis microarray databases provided exploratory expression profiling as a starting point to elucidate PUB function. AtPUB19 and closely related AtPUB18 are notable for their increased expression during abiotic stresses. While condition-directed germination assays showed a decreased sensitivity to salt and ABA for pub18 pub19 double insertion lines, no related change in susceptibility to these or other abiotic stress treatments were seen with condition-directed root growth assays. Thus, this preliminary work has begun to reveal insight into the complex abiotic stress-related roles AtPUB18 and AtPUB19 have during mediation of environmental stress acclimation in Arabidopsis.

The ability of plants to sense and respond to environmental and endogenous signals is essential to their growth and development. As part of these diverse cellular functions, ubiquitin-mediated proteolysis has emerged to be an important process involved in how plant signalling pathways can be regulated in response to such cues. Of the three enzymes involved in linking ubiquitin to protein targets, E3 ubiquitin ligases are of interest as they confer substrate specificity during this ubiquitination process. The overall focal point of this research is on plant U-box (PUB) E3 ubiquitin ligases, a family that has undergone a large gene expansion possibly attributable to the regulation of biological processes unique to the plant life cycle. In Arabidopsis there are 64 predicted PUBs, many for which biological roles have yet to be determined. And as research continues to uncover PUB functions, the functional diversity in the gene family will likely expand. Specifically the focus of this research is on characterizing two ARM repeat-containing PUBs – AtPUB18 and AtPUB19. General analysis of pub18 and pub19 T-DNA insertion lines for growth defects did not yield distinct altered phenotypes. Closer inspection of selected lines showed independent gene assortment phenotypes that, with further inordinately convoluted pursuit, proved to have an AtPUB18/19-unrelated outcome. The availability of Arabidopsis microarray databases provided exploratory expression profiling as a starting point to elucidate PUB function. AtPUB19 and closely related AtPUB18 are notable for their increased expression during abiotic stresses. While condition-directed germination assays showed a decreased sensitivity to salt and ABA for pub18 pub19 double insertion lines, no related change in susceptibility to these or other abiotic stress treatments were seen with condition-directed root growth assays. Thus, this preliminary work has begun to reveal insight into the complex abiotic stress-related roles AtPUB18 and AtPUB19 have during mediation of environmental stress acclimation in Arabidopsis.

No / Beta amyloid plays a main role in the pathophysiology of Alzheimer's disease by inducing oxidative stress in the brain. Curcumin, a natural antioxidant, is known to inhibit beta amyloid and beta amyloid induced oxidative stress. However, low bioavailability and photodegradation are the major concerns for the use of curcumin. In the present study, we have formulated apolipoprotein E3 mediated poly(butyl) cyanoacrylate nanoparticles containing curcumin (ApoE3-C-PBCA) to provide photostability and enhanced cell uptake of curcumin by targeting. Prepared nanoparticles were characterized for particle size, zeta potential, entrapment efficiency and in vitro drug release. The entrapment of curcumin inside the nanoparticles was confirmed by X-ray diffraction analysis. Physicochemical characterization confirmed the suitability of the method of preparation. The photostability of curcumin was increased significantly in nanoparticles compared to plain curcumin. In vitro cell culture study showed enhanced therapeutic efficacy of ApoE3-C-PBCA against beta amyloid induced cytotoxicity in SH-SY5Y neuroblastoma cells compared to plain curcumin solution. Beta amyloid is known to induce apoptosis in neuronal cells, therefore antiapoptotic activity of curcumin was studied using flow cytometry assays. From all the experiments, it was found that the activity of curcumin was enhanced with ApoE3-C-PBCA compared to plain curcumin solution suggesting enhanced cell uptake and a sustained drug release effect. The synergistic effect of ApoE3 and curcumin was also studied, since ApoE3 also possesses both antioxidant and antiamyloidogenic activity. It was found that ApoE3 did indeed have activity against beta amyloid induced cytotoxicity along with curcumin. Hence, ApoE3-C-PBCA offers great advantage in the treatment of beta amyloid induced cytotoxicity in Alzheimer's disease.