Biomedical subjects

Qian Huang

Publications and source records attributed to Qian Huang.

At least 19 recordsLinked to original sources

PubMed2006

Discovery of oxadiazoyl tertiary carbinamine inhibitors of beta-secretase (BACE-1).

We describe the discovery and optimization of tertiary carbinamine derived inhibitors of the enzyme beta-secretase (BACE-1). These novel non-transition-state-derived ligands incorporate a single primary amine to interact with the catalytic aspartates of the target enzyme. Optimization of this series provided inhibitors with intrinsic and functional potency comparable to evolved transition state isostere derived inhibitors of BACE-1.

Amyloid Precursor Protein Secretases↗

PubMed2006

LRRTM3 promotes processing of amyloid-precursor protein by BACE1 and is a positional candidate gene for late-onset Alzheimer's disease.

Rare familial forms of Alzheimer's disease (AD) are thought to be caused by elevated proteolytic production of the Abeta42 peptide from the beta-amyloid-precursor protein (APP). Although the pathogenesis of the more common late-onset AD (LOAD) is not understood, BACE1, the protease that cleaves APP to generate the N terminus of Abeta42, is more active in patients with LOAD, suggesting that increased amyloid production processing might also contribute to the sporadic disease. Using high-throughput siRNA screening technology, we assessed 15,200 genes for their role in Abeta42 secretion and identified leucine-rich repeat transmembrane 3 (LRRTM3) as a neuronal gene that promotes APP processing by BACE1. siRNAs targeting LRRTM3 inhibit the secretion of Abeta40, Abeta42, and sAPPbeta, the N-terminal APP fragment produced by BACE1 cleavage, from cultured cells and primary neurons by up to 60%, whereas overexpression increases Abeta secretion. LRRTM3 is expressed nearly exclusively in the nervous system, including regions affected during AD, such as the dentate gyrus. Furthermore, LRRTM3 maps to a region of chromosome 10 linked to both LOAD and elevated plasma Abeta42, and is structurally similar to a family of neuronal receptors that includes the NOGO receptor, an inhibitor of neuronal regeneration and APP processing. Thus, LRRTM3 is a functional and positional candidate gene for AD, and, given its receptor-like structure and restricted expression, a potential therapeutic target.

Alzheimer Disease↗

PubMed2006

[Transduction efficacy of recombinant type 1 and type 2 adeno-associated virus in the retinal cells].

OBJECTIVE: To investigate the transduction and gene expression of the recombinant adeno-associated viruses (rAAV) of the serotypes 1 and 2 in the retinal cells. METHODS: rAAV vectors of type 1 and type 2 encoding EGFP were infected into the cultured retinal pigmentary epithelium (RPE) cells of the line CRL-2302 and primarily cultured retinal neural cells from normal SD rats, and primarily cultured RPE cells from an adult cornea donor. The cultured RPE cells transduced by rAAV2-EGFP or rAAV2/1-EGFP were harvested at the 7 th and 14 th day after infection to be detected by fluorescence-activated cell sorter. The onset of EGFP gene expression and EGFP positive rate were detected by flow cytometry and fluorescence microscopy. Then, rAAV2/1-EGFP and rAAV2-EGFP were injected into the subretinal spaces of 32 SD rats to investigate the onset of EGFP fluorescence and its distribution in the fundus in vivo via fluorescence stereoscope. HE staining and immunohistochemistry were used to observe the infected cell type and immune response in the retina. RESULTS: The percentage of EGFP positive cells and mean intensity of EGFP fluorescence in the cells transduced by rAAV2-EGFP 7 and 14 days after transduction were 13.50% +/- 1.70% and 15.60% +/- 0.82%, and 2.75 +/- 0.12 and 3.80 +/- 0.72 respectively; and the EGFP positive cells and mean intensity of EGFP fluorescence in the cells transduced by rAAV2/1-EGFP were 1.09% +/- 0.5% and 1.98% +/- 0.45%, and 1.12 +/- 0.09 and 1.75 +/- 0.2 respectively. The EGFP fluorescence area in the retina were (5389 +/- 211) microm(2), (9832 +/- 364) microm(2), (14 454 +/- 446) microm(2), (20 528 +/- 648) microm(2), and (20 264 +/- 683) microm(2) respectively 3, 7, 14, and 75 days, and 4 month after transduction by rAAV2-EGFP in vivo; In the rat retina transduced by rAAV2/1-EGFP, the EGFP fluorescence areas were (9666 +/- 348) microm(2), (12 160 +/- 439) microm(2), (19 794 +/- 621) microm(2), (26 172 +/- 923) microm(2), and (26 022 +/- 965) microm(2) respectively 3, 7, 14, and 75 days, and 4 month after infection. CONCLUSION: rAAV2 efficiently transduces retinal cells both in vitro and in vivo. rAAV2/1 is a more effective gene-transferring vector to be used in retinal cells in vivo than rAAV2.

Animals↗

PubMed2006

Macrocyclic inhibitors of beta-secretase: functional activity in an animal model.

A macrocyclic inhibitor of beta-secretase was designed by covalently cross-linking the P1 and P3 side chains of an isophthalamide-based inhibitor. Macrocyclization resulted in significantly improved potency and physical properties when compared to the initial lead structures. More importantly, these macrocyclic inhibitors also displayed in vivo amyloid lowering when dosed in a murine model.

Amides↗

PubMed2006

[The inhibitory effect of paclitaxel nanoparticles on ovarian cancer xenografts and lymphatic targeting].

OBJECTIVE: To develop a polymeric drug delivery system for paclitaxel and determine whether paclitaxel can inhibit the growth of ovarian carcinoma xenografts in F344 rats by intraperitoneal administration. METHODS: Paclitaxel loading nanoparticles (PLA) were synthesized by ultrasonic emulsification; rat ovarian carcinoma cells were injected into the peritoneal cavity of F344 rats. The antitumor effect of paclitaxel nanoparticles in vivo has been evaluated by measuring tumor weight and ascite volume. At the end of the procedure the rats were killed, tumors were excised and processed for PCNA staining, tissue terminal deoxynucleotide transferase-mediated dUTP nick and labeling (TUNEL) assay. Paclitaxel concentration in plasma, pelvic lymph nodes, liver, heart were determined by high-performance liquid chromatography (HPLC). RESULTS: In the implanted carcinoma cells, paclitaxel nanoparticles significantly reduced tumor weight [(4.55 +/- 0.11) g vs (10.13 +/- 0.52) g]and ascites volume [(3.55 +/- 0.50) mL vs (30.45 +/- 1.55) mL], and induced apoptosis of tumor cells [(105 +/- 15) vs (55 +/- 10)]. The paclitaxel concentration of pelvic lymph nodes in PLA treated animals was significantly higher than that of free PTX treated animals 48 h after intraperitoneal administration [(0.75 +/- 0.05) microg/g vs (0.188 +/- 0.045) microg/g]. CONCLUSION: The intraperitoneal administration of paclitaxel nanoparticles can significantly inhibit the progression of ovarian carcinoma in peritoneal cavity of female F344 rats. The paclitaxel nanoparticle is safe and lymphatic targeting.

Animals↗

PubMed2006

Histone deacetylase activities are required for innate immune cell control of Th1 but not Th2 effector cell function.

Histone deacetylases (HDACs) play a critical role in regulating gene expression and key biological processes. However, how HDACs are involved in innate immunity is little understood. Here, in this first systematic investigation of the role of HDACs in immunity, we show that HDAC inhibition by a small-molecule HDAC inhibitor (HDACi), LAQ824, alters Toll-like receptor 4 (TLR4)-dependent activation and function of macrophages and dendritic cells (DCs). Surprisingly, pan-HDAC inhibition modulates only a limited set of genes involved in distinct arms of immune responses. Specifically, it inhibited DC-controlled T helper 1 (Th1) effector but not Th2 effector cell activation and migration. It also inhibited macrophage- and DC-mediated monocyte but not neutrophil chemotaxis. These unexpected findings demonstrate the high specificity of HDAC inhibition in modulating innate and adaptive immune responses, and highlight the potential for HDACi to alter the Th1 and Th2 balance in therapeutic settings.

Animals↗

PubMed2006

A genome wide analysis of ubiquitin ligases in APP processing identifies a novel regulator of BACE1 mRNA levels.

Proteolysis of beta-amyloid precursor protein (APP) into amyloid beta peptide (Abeta) by beta- and gamma-secretases is a critical step in the pathogenesis of Alzheimer's Disease (AD), but the pathways regulating secretases are not fully characterized. Ubiquitinylation, which is dysregulated in AD, may affect APP processing. Here, we describe a screen for APP processing modulators using an siRNA library targeting 532 predicted ubiquitin ligases. Seven siRNA pools diminished Abeta production. Of these, siRNAs targeting PPIL2 (hCyp-60) suppressed beta-site cleavage. Knockdown of PPIL2 mRNA decreased BACE1 mRNA, while overexpression of PPIL2 cDNA enhanced BACE1 mRNA levels. Microarray analysis of PPIL2 or BACE1 knockdown indicated that genes affected by BACE1 knockdown are a subset of those dependent upon PPIL2; suggesting that BACE1 expression is downstream of PPIL2. The association of PPIL2 with BACE expression and its requirement for Abeta production suggests new approaches to discover disease modifying agents for AD.

Amyloid Precursor Protein Secretases↗

PubMed2006

Gene expression profiles of mouse retinas during the second and third postnatal weeks.

Mouse retina undergoes crucial changes during early postnatal development. By using Affymetrix microarrays, we analyzed gene expression profiles of wild-type 129SvEv/C57BL/6 mouse retinas at postnatal days (P) 7, 10, 14, 18, and 21 and found significantly altered expression of 355 genes. Characterization of these 355 genes provided insight into physiologic and pathologic processes of mouse retinal development during the second and third postnatal weeks, a period that corresponds to human embryogenesis between weeks 12 and 28. These genes formed 6 groups with similar change patterns. Among the genes, sixteen cause retinal diseases when mutated; most of these 16 genes were upregulated in retina during this period. Using the PathArt program, we identified the biological processes in which many of the 355 gene products function. Among the most active processes in the P7-P21 retina are those involved in neurogenesis, obesity, diabetes type II, apoptosis, growth and differentiation, and protein kinase activity. We examined the expression patterns of 58 genes in P7 and adult retinas by searching the Brain Gene Expression Map database. Although most genes were present in various cell types in retinas, many displayed high levels of expression specifically in the outer nuclear, inner nuclear, and/or ganglion cell layers. By combining our 3 analyses, we demonstrated that during this period of mouse retinal development, many genes play important roles in various cell types, multiple pathways are involved, and some genes in a pathway are expressed in coordinated patterns. Our results thus provide foundation for future detailed studies of specific genes and pathways in various genetic and environmental conditions during retinal development.

Aging↗

PubMed2006

Paclitaxel nanoparticle inhibits growth of ovarian cancer xenografts and enhances lymphatic targeting.

OBJECTIVES: Ovarian cancer has the highest mortality of all the gynecologic cancers. The antitumor agent paclitaxel has been proved to be efficient in the treatment of ovarian cancer. Our study is to develop a polymeric drug delivery system for paclitaxel and determine whether paclitaxel nanoparticle can inhibit growth of ovarian carcinoma xenografts in Fisher344 (F344) rats by intraperitoneal administration. The mechanism of paclitaxel nanoparticles in rats bearing ovarian cancer has been investigated in this study. METHODS: Synthesize paclitaxel loading nanoparticle (PLA) by ultrasonic emulsification; MTT analysis identified cytotoxic activity of paclitaxel nanoparticle in vitro; rat ovarian carcinoma cells were injected into the peritoneal cavity of F344 rats. The antitumor effect of paclitaxel nanoparticle in vivo has been evaluated by measuring tumor weight and ascite volume. At the end of the procedure rats were sacrificed; tumors were excised and processed for PCNA staining, tissue terminal deoxynucleotide transferase-mediated dUTP nick and labeling assay and RT-PCR to evaluate the proliferative and apoptotic changes and cancer transfer-related gene expression induced by PLA. Paclitaxel concentration in plasma, pelvic lymph nodes, liver, and heart were determined by high-performance liquid chromatography. RESULTS: Paclitaxel nanoparticle and PTX (Cremophor) showed equivalent cytotoxic activity in vitro. In rats implanted carcinoma cells, paclitaxel nanoparticles significantly reduced tumor weight and ascites volume, and induced apoptosis of tumor cells. PLA also inhibited cell proliferation and matrix metalloproteinase 9 mRNA expression. The paclitaxel concentration of pelvic lymph nodes in PLA treated animals was 20-fold higher than that of free PTX treated animals at 48 h after intraperitoneal administration. CONCLUSION: The intraperitoneal administration of paclitaxel nanoparticle can significantly inhibit the progression of ovarian carcinoma in peritoneal cavity of female F344 rat. The paclitaxel nanoparticle is safe and lymphatic targeting.

Animals↗

PubMed2006

BACE-1 inhibition by a series of psi[CH2NH] reduced amide isosteres.

A series of beta-site amyloid precursor protein cleaving enzyme (BACE-1) inhibitors containing a psi(CH2NH) reduced amide bond were synthesized. Incorporation of this reduced amide isostere as a non-cleavable peptide surrogate afforded inhibitors possessing low nanomolar potencies in both an enzymatic and cell-based assay.

Amides↗

PubMed2006

[Subretinal transplantation of human fetal lung fibroblasts expressed ciliary neurotrophic factor gene prevent photoreceptor degeneration in RCS rats].

OBJECTIVE: To investigate the efficacy of subretinal transplantation of CNTF gene transfected fibroblasts for preventing photoreceptor degeneration in RCS. METHODS: The human fetal lung fibroblasts with high level expression of CNTF were established by liposome mediated gene transfer and MTX selection. A 5 microl of cell suspension, containing 1 x 10(5) cells, was injected through pars plana of ciliary body into the subretinal space of the right eye at postnatal 4-5 weeks, the left eye was left without injection or injected with PBS as controls. The both eyes were enucleated for histopathological examinations at 2, 4, 6, 8, 10, 12 and 15 weeks following transplantation. RESULTS: The level of CNTF protein (91,046.15 pg/ml) expressed in the transfected cells was determined by sandwich enzyme-linked immunosorbent assay (ELISA). The four of seven eyes examined by light microscopy and the ten of 14 eyes examined by electro microscopy showed rescue effect. The prolonged photoreceptor survival, reduction of apoptotic cells and debris were observed in transplanted eyes in comparison with untreated or sham-injected eyes. CONCLUSION: This study provides the first indication that transplanted human fibroblasts with high level expression of CNTF are able to rescue photoreceptor degeneration in RCS dystrophic rat retina.

Animals↗

PubMed2006

[Impact of acupuncture on NP-1 expression in spared dorsal root ganglion].

OBJECTIVE: To investigate the impact of acupuncture on NP-1 expression in spared dorsal root ganglion (DRG). METHODS: Twenty-five male adult cats were divided into five groups. The five cats in the pseudo-operation group were kept intact. Ten cats were subjected to unilateral root rhizotomy(unilateral L1-L5 DRGs were transected, but L6 DRG was spared), with five sacrificed seven days later and another five sacrificed 14 days later. Ten cats with unilateral root rhizotomy received acupuncture (electron-needle stimulation in Zusanli, Xuanzhong, Futu and Sanyinjiao which are located in the distribution area of L6 spinal nerve) for 30 minutes per day. Five cats in the acupuncture group were sacrificed seven days and 14 days later respectively. The L6 DRG from the experimental side of each animal was taken and made into frozen sections 20 microm in thickness. The sections were stained under the same conditions using NP-1 specific antibody (1:600, Santa) by immunohistochemistry ABC method. The amounts of NP-1 immunoreaction neurons of DRG were measured. RESULTS: The NP-1 immunoreactants were mainly located in the small and medium-sized neurons and a few large sized neurons in the cats of the pseudo-operation group. Less NP-1 positive medium-small sized neurons were found seven days after partial dorsal root rhizotomy (P<0.05). But they returned back to the original level 14 days after operation. The NP-1 positive large neurons had no significant changes after operations. With seven days of acupuncture, the amounts of NP-1 positive small and medium-sized neurons increased significantly (P<0.05) but were still less than the original level (P<0.05). There were no differences in neurons 14 days after operations between the acupuncture and non-acupuncture group (P>0.05) and between the groups with seven days acupuncture and 14 days of acupuncture (P>0.05). CONCLUSION: Acupuncture increases the expression of NP-1 in small and medium-sized neurons of spared DRG.

Acupuncture↗

PubMed2006

[Characteristics of computed tomography of allergic fungal sinusitis].

OBJECTIVE: To sum up the characteristics of computed tomography of allergic fungal sinusitis (AFS) and to compare the CT changes with the findings in the operation. The diagnostic role of CT scan was discussed. METHODS: The CT scans of 21 patients diagnosed as AFS were analyzed. The patients ranged from 15 to 50 years old,there were 17 males and 4 females. The CT was scanned with both bony and soft tissue windows. The preoperative examinations included nasal endoscopy, skin prick test, total serum IgE and nasal secretion smear. The findings in the operation were compared with the preoperative CT scans. Histopathology and fungal smear were done postoperatively. RESULTS: Endoscopy showed that all patients had polyps with wasfy yellow or inspissated white secretion. Nine cases (11 sides) showed yellow-to-brown material similar to peanut butter in the nasal cavities. Nasal CT scan demonstrated unilateral lesion in 10 cases (10 sides) and bilateral lesions in 11 cases (22 sides), who were all pansinus diseases. CT scan demonstrated a sheet areas of high-attenuation like "ground glass" within sinuses coupled with soft tissue image around them. Bone erosion of anterior skull base was encountered in 3 cases (4 sides). One case showed the intracranial extension. Twenty cases had conceived nasal endoscopic sinus surgeries. One case underwent endoscopic sinus surgery combined with coronal approach. The yellow-to-brown material (allergic mucin) was detected in the cavities of 17 cases. Four cases had green-to-brown secretion like mud. After follow-up of 6 months to 7 years, 14 cases were cured, 7 cases improved. Among them, 3 cases had to get revision surgeries because of recurrence 2 years after surgery. CONCLUSIONS: The characteristic of a sheet area of high-attenuation like " ground glass" within sinuses coupled with soft tissue image around them in computed tomography of nasal sinus, accompanied with invasive expansion or bone erosion, has a diagnostic significance for AFS.

Adolescent↗

PubMed2006

[The construction of recombinant adenovirus expressing bifunctional fusion protein sCAR-EGF and the detection of its activity].

To improve the targeting of adenovirus vector for gene therapy, a fusion gene sCAR-EGF, in which epidermal growth factor gene was fused to the 3' end of extracellular Coxsackie virus-adenovirus receptor gene, was constructed and cloned into shuttle plasmid pDC315 to obtain a recombinant plasmid pDC315-sCAR-EGF. With the AdMax system, AD-293 cells were co-transfected with pDC315-sCAR-EGF and adenovirus genomic plasmid pBHGloxdeltaE13cre. Through high efficiency site specific recombination, a replication-defective adenovirus Ad5-CMV-sCAR-EGF was constructed. The recombinant adenovirus was analyzed by PCR and Western blotting, the results indicated that Ad5-CMV-sCAR-EGF contained the fusion gene sCAR-EGF, and the adenovirus infected cells was induced to produce and secrete the fusion protein into the supernatant. We have demonstrated that the fusion protein sCAR-EGF is helpful for elevating the infection efficiency of Ad5-CMV-luc with the reporter gene in vitro, which providing a new approach to the gene therapy for tumors overexpressing EGFR.

Adenoviridae↗

PubMed2005

Biodegradable hyaluronic acid/n-carboxyethyl chitosan/protein ternary complexes as implantable carriers for controlled protein release.

An ampholytic N-carboxyethyl chitosan (CEC), with various isoelectric points (IPs), was synthesized by grafting acrylic acid on chitosan utilizing Michael's reaction. Compared to native chitosan, CEC has enhanced water solubility and dramatically accelerated enzymatic degradation; the rate of degradation is proportional to the degree of substitution (DS). The results from turbidimetric titration and fluorescence studies revealed that CEC formed complexes with either hyaluronic acid (HA) or bovine serum albumin (BSA) within a certain pH range. The HA/CEC/BSA ternary complexes could be prepared by colloid titration with quantitative yield and BSA entrapment. The rate of BSA release from the complexes was affected by pH, ionic strength, DS of CEC, and the molecular weight (MW) of HA. The endurance of BSA release from the complexes could be extended up to 20 d by formulating them with high-MW HA and CEC with low DS.BSA release profiles from HA/CEC-2/BSA complexes.

Absorbable Implants↗

PubMed2005

Distinct gene expression profiles and reduced JNK signaling in retinitis pigmentosa caused by RP1 mutations.

To understand the mechanisms underlying autosomal dominant progressive retinitis pigmentosa (RP) caused by the mutations of the RP1 gene and to identify molecules that play roles in the early disease process, we used Affymetrix U74Av2 microarrays to compare the gene expression profiles of retinas from Rp1-/- and Rp1+/+ mice at postnatal days (P) 7, 10, 14, 18 and 21. These profiles were independently verified by comparison with results of retinal serial analysis of gene expression, U74Av2 array studies of mouse retinas, real-time PCR and in situ hybridization. We found that the disruption of Rp1 significantly affected the expression of multiple clusters of genes whose products were involved in diverse biological pathways. The molecular responses to the disruption of Rp1 changed dramatically during development and were distinct from responses to the disruption of photoreceptor transcription factors (Crx-/- or Nrl-/-) and a phototransduction molecule (Pde6brd1). We found specific alterations of gene expression in the c-Jun N-terminal kinase (JNK) signaling cascades. Western analysis confirmed that the phosphorylation of key members in the JNK signaling cascades (i.e. JNK1, JNK2, MAP2, MKK4 and c-Jun) is reduced, whereas phospho-ERK and phospho-p38 are unchanged, in Rp1-/- retinas at P18-21. Immunostaining demonstrated that, like Rp1, phospho-JNKs and phospho-MAP2 are present in outer segments of photoreceptors. Our studies reveal unique molecular phenotypes in multiple biological pathways and the specific reduction of JNK signaling cascades in RP1 diseases, and suggest that RP1, a doublecortin-containing microtubule associated protein, and JNK signaling cascades play integral roles in photoreceptor development and maintenance. Our studies further suggest JNK-related therapeutic strategies for RP1 diseases.

Animals↗

PubMed2005

Compounds that bind APP and inhibit Abeta processing in vitro suggest a novel approach to Alzheimer disease therapeutics.

Extracellular deposits of aggregated amyloid-beta (Abeta) peptides are a hallmark of Alzheimer disease; thus, inhibition of Abeta production and/or aggregation is an appealing strategy to thwart the onset and progression of this disease. The release of Abeta requires processing of the amyloid precursor protein (APP) by both beta- and gamma-secretase. Using an assay that incorporates full-length recombinant APP as a substrate for beta-secretase (BACE), we have identified a series of compounds that inhibit APP processing, but do not affect the cleavage of peptide substrates by BACE1. These molecules also inhibit the processing of APP and Abeta by BACE2 and selectively inhibit the production of Abeta(42) species by gamma-secretase in assays using CTF99. The compounds bind directly to APP, likely within the Abeta domain, and therefore, unlike previously described inhibitors of the secretase enzymes, their mechanism of action is mediated through APP. These studies demonstrate that APP binding agents can affect its processing through multiple pathways, providing proof of concept for novel strategies aimed at selectively modulating Abeta production.

Alzheimer Disease↗

PubMed2005

Novel mutations introduced at the beta-site of amyloid beta protein precursor enhance the production of amyloid beta peptide by BACE1 in vitro and in cells.

Abnormal production and accumulation of amyloid-beta peptide (Abeta) plays a major role in the pathogenesis of Alzheimer's disease (AD). beta-secretase (BACE1) is responsible for the cleavage at thebeta-site in amyloid beta protein precursor (AbetaPP/APP) to generate the N-terminus of Abeta. Here we report the stepwise identification and characterization of a novel APP-beta-site mutant, "NFEV" (APP_NFEV) in vitro and in cells. In vitro, the APP_NFEV exhibits 100-fold enhanced cleavage rate relative to the "wild-type" substrate (APPwt) and 10-fold increase relative to the Swedish-type mutation variant (APPsw). In cells, it was preferably cleaved among 24 APP beta-site mutations tested. More importantly, the APP_NFEV mutant failed to generate any detectable Abeta peptides in BACE1-KO mouse fibroblast cells. The production of Abeta peptides was restored by co-transfecting human BACE1, demonstrating that BACE1 is the only enzyme responsible for the processing of APP_NFEV in these cells. Analysis of APP_NFEV cleavage products secreted in the media revealed that in cells BACE1 cleaves APP_NFEV at the position between NF and EV, identical to that observed in vitro. A BACE inhibitor blocked the processing of the APP_NFEV beta-site in vitro and in cells. Our data indicates that the "NFEV" mutant is not only an enhanced substrate for BACE1 in vitro, but also a specific substrate for BACE1 in cells.

Alzheimer Disease↗