{"entity": "researcher", "timestamp": "2026-06-17T20:22:55.006Z", "family": "Williams", "given": "Pete A", "initials": "PA", "orcid": "0000-0001-6194-8397", "affiliations": ["Division of Eye and Vision, Department of Clinical Neuroscience, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden. pete.williams@ki.se."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/0b4d7eb42dcd4c489a97198a043b3806.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/0b4d7eb42dcd4c489a97198a043b3806"}}, "publications": [{"entity": "publication", "iuid": "e68983c84bbc41d8a88758e197b58a33", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e68983c84bbc41d8a88758e197b58a33.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e68983c84bbc41d8a88758e197b58a33"}}, "title": "Potent Neuronal Nicotinamide Adenine Dinucleotide-Boosting Tetrahydroquinoxalines: Structure-Activity Relationships and Early Drug Metabolism and Pharmacokinetics Evaluation.", "authors": [{"family": "Cu\u0159\u00ednov\u00e1", "given": "Petra", "initials": "P", "orcid": "0000-0001-8264-7032", "researcher": {"href": "https://publications.scilifelab.se/researcher/f196559d7e954e448879878768bc213e.json"}}, {"family": "J\u00f6e", "given": "Melissa", "initials": "M"}, {"family": "Cesar", "given": "Filip", "initials": "F"}, {"family": "Nicol", "given": "Alan", "initials": "A"}, {"family": "Schwan", "given": "Kristi\u00e1n", "initials": "K"}, {"family": "Kohout", "given": "Michal", "initials": "M", "orcid": "0000-0003-1447-4453", "researcher": {"href": "https://publications.scilifelab.se/researcher/a4f2547f153b43d79c0364607cd518c6.json"}}, {"family": "Varrichio", "given": "Carmine", "initials": "C"}, {"family": "Saleh", "given": "Aljona", "initials": "A"}, {"family": "Wheelock", "given": "Craig E", "initials": "CE", "orcid": "0000-0002-8113-0653", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3cd2b99e3e9486ba41030c809a48c51.json"}}, {"family": "J\u00f3hannesson", "given": "Gauti", "initials": "G"}, {"family": "Eigner", "given": "V\u00e1clav", "initials": "V"}, {"family": "Tribble", "given": "James R", "initials": "JR"}, {"family": "Brancale", "given": "Andrea", "initials": "A", "orcid": "0000-0002-9728-3419", "researcher": {"href": "https://publications.scilifelab.se/researcher/7aa54df57e794ee3a2b98108bd694277.json"}}, {"family": "Williams", "given": "Pete A", "initials": "PA", "orcid": "0000-0001-6194-8397", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b4d7eb42dcd4c489a97198a043b3806.json"}}], "type": "journal article", "published": "2026-04-09", "journal": {"title": "ACS Med Chem Lett", "issn": "1948-5875", "volume": "17", "issue": "4", "pages": "916-924", "issn-l": "1948-5875"}, "abstract": "We designed and synthesized a series of novel 1,2,3,4-tetrahydroquinoxaline derivatives and evaluated their ability to increase nicotinamide adenine dinucleotide (NAD) levels in primary cortical neurons. Several compounds demonstrated nanomolar potency and enabled the establishment of clear structure-activity relationships (SAR), highlighting key substituents required for activity. Qualitative 3DSAR analysis further identified favorable steric, electrostatic, and hydrophobic features associated with NAD enhancement. Selected lead compounds were assessed for in vitro drug metabolism and pharmacokinetics (DMPK) properties, showing good cell permeability and species-dependent metabolic stability in liver microsomes, with improved stability in human systems compared with rodent systems. These findings identify tetrahydroquinoxalines as a promising class of neuronal NAD-boosting agents and provide a strong foundation for further optimization toward neuroprotective drug candidates.", "doi": "10.1021/acsmedchemlett.6c00058", "pmid": "41982735", "labels": {"Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13071616"}], "notes": [], "created": "2026-05-14T20:21:50.854Z", "modified": "2026-05-14T20:21:51.275Z"}, {"entity": "publication", "iuid": "938637baf52e4a34b96c832e290bf195", "links": {"self": {"href": "https://publications.scilifelab.se/publication/938637baf52e4a34b96c832e290bf195.json"}, "display": {"href": "https://publications.scilifelab.se/publication/938637baf52e4a34b96c832e290bf195"}}, "title": "Oral nicotinamide provides robust, dose-dependent structural and metabolic neuroprotection of retinal ganglion cells in experimental glaucoma.", "authors": [{"family": "Cimaglia", "given": "Gloria", "initials": "G"}, {"family": "Tribble", "given": "James R", "initials": "JR"}, {"family": "Votruba", "given": "Marcela", "initials": "M"}, {"family": "Williams", "given": "Pete A", "initials": "PA", "orcid": "0000-0001-6194-8397", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b4d7eb42dcd4c489a97198a043b3806.json"}}, {"family": "Morgan", "given": "James E", "initials": "JE"}], "type": "journal article", "published": "2024-08-23", "journal": {"title": "Acta Neuropathol Commun", "issn": "2051-5960", "volume": "12", "issue": "1", "pages": "137", "issn-l": "2051-5960"}, "abstract": "A compromised capacity to maintain NAD pools is recognized as a key underlying pathophysiological feature of neurodegenerative diseases. NAD acts as a substrate in major cell functions including mitochondrial homeostasis, cell signalling, axonal transport, axon/Wallerian degeneration, and neuronal energy supply. Dendritic degeneration is an early marker of neuronal stress and precedes cell loss. However, little is known about dendritic structural preservation in pathologic environments and remodelling in mature neurons. Retinal ganglion cell dendritic atrophy is an early pathological feature in animal models of the disease and has been demonstrated in port-mortem human glaucoma samples. Here we report that a nicotinamide (a precursor to NAD through the NAD salvage pathway) enriched diet provides robust retinal ganglion cell dendritic protection and preserves dendritic structure in a rat model of experimental glaucoma. Metabolomic analysis of optic nerve samples from the same animals demonstrates that nicotinamide provides robust metabolic neuroprotection in glaucoma. Advances in our understanding of retinal ganglion cell metabolic profiles shed light on the energetic shift that triggers early neuronal changes in neurodegenerative diseases. As nicotinamide can improve visual function short term in existing glaucoma patients, we hypothesize that a portion of this visual recovery may be due to dendritic preservation in stressed, but not yet fully degenerated, retinal ganglion cells.", "doi": "10.1186/s40478-024-01850-8", "pmid": "39180087", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11342512"}, {"db": "pii", "key": "10.1186/s40478-024-01850-8"}], "notes": [], "created": "2024-11-26T10:28:13.705Z", "modified": "2025-10-17T13:03:13.062Z"}, {"entity": "publication", "iuid": "d68829091e754b1588f7bb708628ede4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d68829091e754b1588f7bb708628ede4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d68829091e754b1588f7bb708628ede4"}}, "title": "Pyrroloquinoline quinone drives ATP synthesis in vitro and in vivo and provides retinal ganglion cell neuroprotection.", "authors": [{"family": "Canovai", "given": "Alessio", "initials": "A"}, {"family": "Tribble", "given": "James R", "initials": "JR"}, {"family": "J\u00f6e", "given": "Melissa", "initials": "M"}, {"family": "Westerlund", "given": "Daniela Y", "initials": "DY"}, {"family": "Amato", "given": "Rosario", "initials": "R"}, {"family": "Trounce", "given": "Ian A", "initials": "IA"}, {"family": "Dal Monte", "given": "Massimo", "initials": "M"}, {"family": "Williams", "given": "Pete A", "initials": "PA", "orcid": "0000-0001-6194-8397", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b4d7eb42dcd4c489a97198a043b3806.json"}}], "type": "journal article", "published": "2023-09-08", "journal": {"title": "Acta Neuropathol Commun", "issn": "2051-5960", "volume": "11", "issue": "1", "pages": "146", "issn-l": "2051-5960"}, "abstract": "Retinal ganglion cells are highly metabolically active requiring strictly regulated metabolism and functional mitochondria to keep ATP levels in physiological range. Imbalances in metabolism and mitochondrial mechanisms can be sufficient to induce a depletion of ATP, thus altering retinal ganglion cell viability and increasing cell susceptibility to death under stress. Altered metabolism and mitochondrial abnormalities have been demonstrated early in many optic neuropathies, including glaucoma, autosomal dominant optic atrophy, and Leber hereditary optic neuropathy. Pyrroloquinoline quinone (PQQ) is a quinone cofactor and is reported to have numerous effects on cellular and mitochondrial metabolism. However, the reported effects are highly context-dependent, indicating the need to study the mechanism of PQQ in specific systems. We investigated whether PQQ had a neuroprotective effect under different retinal ganglion cell stresses and assessed the effect of PQQ on metabolic and mitochondrial processes in cortical neuron and retinal ganglion cell specific contexts. We demonstrated that PQQ is neuroprotective in two models of retinal ganglion cell degeneration. We identified an increased ATP content in healthy retinal ganglion cell-related contexts both in in vitro and in vivo models. Although PQQ administration resulted in a moderate effect on mitochondrial biogenesis and content, a metabolic variation in non-diseased retinal ganglion cell-related tissues was identified after PQQ treatment. These results suggest the potential of PQQ as a novel neuroprotectant against retinal ganglion cell death.", "doi": "10.1186/s40478-023-01642-6", "pmid": "37684640", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10486004"}, {"db": "pii", "key": "10.1186/s40478-023-01642-6"}], "notes": [], "created": "2023-12-03T19:51:02.919Z", "modified": "2025-10-17T13:03:13.487Z"}]}