{"entity": "journal", "iuid": "aff531fbe92c42a6b8b543e2e31552b5", "timestamp": "2026-03-10T03:56:31.308Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/journal/Biomolecules.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/journal/Biomolecules"}}, "title": "Biomolecules", "issn": "2218-273X", "issn-l": null, "publications_count": 2, "publications": [{"entity": "publication", "iuid": "3b57bb09004f426986f1ebf1a308b627", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/3b57bb09004f426986f1ebf1a308b627.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/3b57bb09004f426986f1ebf1a308b627"}}, "title": "Nradd Acts as a Negative Feedback Regulator of Wnt/\u03b2-Catenin Signaling and Promotes Apoptosis.", "authors": [{"family": "Ozalp", "given": "Ozgun", "initials": "O"}, {"family": "Cark", "given": "Ozge", "initials": "O"}, {"family": "Azbazdar", "given": "Yagmur", "initials": "Y"}, {"family": "Haykir", "given": "Betul", "initials": "B"}, {"family": "Cucun", "given": "Gokhan", "initials": "G"}, {"family": "Kucukaylak", "given": "Ismail", "initials": "I"}, {"family": "Alkan-Yesilyurt", "given": "Gozde", "initials": "G"}, {"family": "Sezgin", "given": "Erdinc", "initials": "E", "orcid": "0000-0002-4915-388X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f7bd3619c7fd48318bc4c1e7a9910df8.json"}}, {"family": "Ozhan", "given": "Gunes", "initials": "G", "orcid": "0000-0002-4806-5917", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2294b051364e4b6e8cb1008c500b41af.json"}}], "type": "journal article", "published": "2021-01-14", "journal": {"title": "Biomolecules", "issn": "2218-273X", "volume": "11", "issue": "1", "issn-l": null}, "abstract": "Wnt/\u03b2-catenin signaling controls many biological processes for the generation and sustainability of proper tissue size, organization and function during development and homeostasis. Consequently, mutations in the Wnt pathway components and modulators cause diseases, including genetic disorders and cancers. Targeted treatment of pathway-associated diseases entails detailed understanding of the regulatory mechanisms that fine-tune Wnt signaling. Here, we identify the neurotrophin receptor-associated death domain (Nradd), a homolog of p75 neurotrophin receptor (p75NTR), as a negative regulator of Wnt/\u03b2-catenin signaling in zebrafish embryos and in mammalian cells. Nradd significantly suppresses Wnt8-mediated patterning of the mesoderm and neuroectoderm during zebrafish gastrulation. Nradd is localized at the plasma membrane, physically interacts with the Wnt receptor complex and enhances apoptosis in cooperation with Wnt/\u03b2-catenin signaling. Our functional analyses indicate that the N-glycosylated N-terminus and the death domain-containing C-terminus regions are necessary for both the inhibition of Wnt signaling and apoptosis. Finally, Nradd can induce apoptosis in mammalian cells. Thus, Nradd regulates cell death as a modifier of Wnt/\u03b2-catenin signaling during development.", "doi": "10.3390/biom11010100", "pmid": "33466728", "labels": {"SciLifeLab Fellow": null, "Erdinc Sezgin": null}, "xrefs": [{"db": "pmc", "key": "PMC7828832"}, {"db": "pii", "key": "biom11010100"}], "notes": [], "created": "2022-12-01T12:42:20.916Z", "modified": "2022-12-01T12:42:20.974Z"}, {"entity": "publication", "iuid": "602f6de7dd804796b73a794658ed41e8", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/602f6de7dd804796b73a794658ed41e8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/602f6de7dd804796b73a794658ed41e8"}}, "title": "Histidyl-Proline Diketopiperazine Isomers as Multipotent Anti-Alzheimer Drug Candidates.", "authors": [{"family": "Turkez", "given": "Hasan", "initials": "H"}, {"family": "Cacciatore", "given": "Ivana", "initials": "I"}, {"family": "Arslan", "given": "Mehmet Enes", "initials": "ME"}, {"family": "Fornasari", "given": "Erika", "initials": "E"}, {"family": "Marinelli", "given": "Lisa", "initials": "L"}, {"family": "Di Stefano", "given": "Antonio", "initials": "A", "orcid": "0000-0002-3042-2234", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/413d1857e18c4eef8929bb9ceedc5af0.json"}}, {"family": "Mardinoglu", "given": "Adil", "initials": "A"}], "type": "journal article", "published": "2020-05-09", "journal": {"title": "Biomolecules", "issn": "2218-273X", "issn-l": null, "volume": "10", "issue": "5", "pages": "737"}, "abstract": "Cyclic dipeptides administered by both parenteral and oral routes are suggested as promising candidates for the treatment of neurodegeneration-related pathologies. In this study, we tested Cyclo (His-Pro) isomers (cHP1-4) for their anti-Alzheimer potential using a differentiated human neuroblastoma cell line (SH-SY5Y) as an Alzheimer's disease (AD) experimental model. The SH-SY5Y cell line was differentiated by the application of all-trans retinoic acid (RA) to obtain mature neuron-like cells. Amyloid-beta 1-42 (A\u03b2) peptides, the main effector in AD, were administered to the differentiated cell cultures to constitute the in vitro disease model. Next, we performed cell viability analyses 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays) to investigate the neuroprotective concentrations of cyclodipeptides using the in vitro AD model. We evaluated acetylcholinesterase (AChE), \u03b1- and \u03b2-secretase activities (TACE and BACE1), antioxidant potency, and apoptotic/necrotic properties and performed global gene expression analysis to understand the main mechanism behind the neuroprotective features of cHP1-4. Moreover, we conducted sister chromatid exchange (SCE), micronucleus (MN), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) analyses to evaluate the genotoxic damage potential after applications with cHP1-4 on cultured human lymphocytes. Our results revealed that cHP1-4 isomers provide a different degree of neuroprotection against 1-42A\u03b2-induced cell death on the in vitro AD model. The applications with cHP1-4 isomers altered the activity of AChE but not the activity of TACE and BACE1. Our analysis indicated that the cHP1-4 increased the total antioxidant capacity without altering total oxidative status levels in the cellular AD model and that cHP1-4 modulated the alterations of gene expressions by 1-42A\u03b2 exposure. We also observed that cHP1-4 exhibited noncytotoxic and non-genotoxic features in cultured human whole blood cells. In conclusion, cHP1-4 isomers, especially cHP4, have been explored as novel promising therapeutics against AD.1-42", "doi": "10.3390/biom10050737", "pmid": "32397415", "labels": {"Adil Mardinoglu": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "biom10050737"}, {"db": "pmc", "key": "PMC7277666"}], "notes": [], "created": "2020-11-30T03:11:36.175Z", "modified": "2022-11-04T11:32:15.009Z"}], "created": "2020-11-30T03:11:36.190Z", "modified": "2020-11-30T03:11:36.190Z"}