{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:53:26Z","timestamp":1791262406176,"version":"4.1.0"},"reference-count":38,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.bioorg.2026.110526","type":"journal-article","created":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T14:11:52Z","timestamp":1789308712000},"page":"110526","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Lipid-conjugated siRNA targeting SARM1 enables CNS silencing and mitigates alzheimer-like phenotypes"],"prefix":"10.1016","volume":"182","author":[{"given":"Ying","family":"Cai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongqiong","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihui","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enhua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhe","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianwen","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghui","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingshan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bioorg.2026.110526_bb0005","article-title":"Therapeutic siRNA: state of the art","volume":"5","author":"Hu","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.bioorg.2026.110526_bb0010","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s40259-022-00549-3","article-title":"Therapeutic siRNA: state-of-the-art and future perspectives","volume":"36","author":"Friedrich","year":"2022","journal-title":"BioDrugs"},{"key":"10.1016\/j.bioorg.2026.110526_bb0015","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41576-021-00439-4","article-title":"Drug delivery systems for RNA therapeutics","volume":"23","author":"Paunovska","year":"2022","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.bioorg.2026.110526_bb0020","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1038\/s41587-022-01334-x","article-title":"Expanding RNAi therapeutics to extrahepatic tissues with lipophilic conjugates","volume":"40","author":"Brown","year":"2022","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.bioorg.2026.110526_bb0025","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","article-title":"Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?","volume":"17","author":"Leng","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.bioorg.2026.110526_bb0030","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41572-021-00269-y","article-title":"Alzheimer disease","volume":"7","author":"Knopman","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"10.1016\/j.bioorg.2026.110526_bb0035","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10753-022-01721-1","article-title":"Neuroinflammation in Alzheimer\u2019s disease: current Progress in molecular Signaling and therapeutics","volume":"46","author":"Thakur","year":"2023","journal-title":"Inflammation"},{"key":"10.1016\/j.bioorg.2026.110526_bb0040","doi-asserted-by":"crossref","DOI":"10.3390\/molecules29215131","article-title":"Recent advances in therapeutics for the treatment of Alzheimer\u2019s disease","volume":"29","author":"Thawabteh","year":"2024","journal-title":"Molecules"},{"key":"10.1016\/j.bioorg.2026.110526_bb0045","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in early Alzheimer\u2019s disease","volume":"388","author":"van Dyck","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.bioorg.2026.110526_bb0050","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41392-024-01911-3","article-title":"Recent advances in Alzheimer\u2019s disease: mechanisms, clinical trials and new drug development strategies","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.bioorg.2026.110526_bb0055","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1097\/JCMA.0000000000001252","article-title":"A 2025 update on treatment strategies for the Alzheimer\u2019s disease spectrum","volume":"88","author":"Wu","year":"2025","journal-title":"J. Chin. Med. Assoc."},{"key":"10.1016\/j.bioorg.2026.110526_bb0060","doi-asserted-by":"crossref","DOI":"10.1016\/j.nbd.2020.104832","article-title":"The wrinkling of time: aging, inflammation, oxidative stress, and the circadian clock in neurodegeneration","volume":"139","author":"Lananna","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.bioorg.2026.110526_bb0065","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.1167\/iovs.12-10973","article-title":"Excitotoxicity upregulates SARM1 protein expression and promotes Wallerian-like degeneration of retinal ganglion cells and their axons","volume":"54","author":"Massoll","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.bioorg.2026.110526_bb0070","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s12974-025-03423-5","article-title":"Targeting SARM1 as a novel neuroprotective therapy in neurotropic viral infections","volume":"22","author":"He","year":"2025","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.bioorg.2026.110526_bb0075","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/j.neuron.2021.03.021","article-title":"An NAD+\/NMN balancing act by SARM1 and NMNAT2 controls axonal degeneration","volume":"109","author":"Waller","year":"2021","journal-title":"Neuron"},{"key":"10.1016\/j.bioorg.2026.110526_bb0080","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.neuron.2021.02.009","article-title":"SARM1 is a metabolic sensor activated by an increased NMN\/NAD(+) ratio to trigger axon degeneration","volume":"109","author":"Figley","year":"2021","journal-title":"Neuron"},{"key":"10.1016\/j.bioorg.2026.110526_bb0085","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2020.115644","article-title":"Identification of the first noncompetitive SARM1 inhibitors","volume":"28","author":"Loring","year":"2020","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bioorg.2026.110526_bb0090","doi-asserted-by":"crossref","first-page":"13846","DOI":"10.1038\/s41598-022-18052-8","article-title":"Natural variants of human SARM1 cause both intrinsic and dominant loss-of-function influencing axon survival","volume":"12","author":"Ademi","year":"2022","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bioorg.2026.110526_bb0095","doi-asserted-by":"crossref","DOI":"10.1016\/j.molcel.2022.03.007","article-title":"Structural basis of SARM1 activation, substrate recognition, and inhibition by small molecules","volume":"82","author":"Shi","year":"2022","journal-title":"Mol. Cell"},{"key":"10.1016\/j.bioorg.2026.110526_bb0100","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.neures.2024.09.005","article-title":"SARM1 is essential for NMDA receptor-dependent endocytosis of AMPA receptors in hippocampal neurons","volume":"210","author":"Morishita","year":"2025","journal-title":"Neurosci. Res."},{"key":"10.1016\/j.bioorg.2026.110526_bb0105","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1016\/j.neuron.2017.02.022","article-title":"The SARM1 toll\/interleukin-1 receptor domain possesses intrinsic NAD(+) cleavage activity that promotes pathological axonal degeneration","volume":"93","author":"Essuman","year":"2017","journal-title":"Neuron"},{"key":"10.1016\/j.bioorg.2026.110526_bb0110","doi-asserted-by":"crossref","first-page":"3226","DOI":"10.1093\/brain\/awab184","article-title":"Pharmacological SARM1 inhibition protects axon structure and function in paclitaxel-induced peripheral neuropathy","volume":"144","author":"Bosanac","year":"2021","journal-title":"Brain"},{"key":"10.1016\/j.bioorg.2026.110526_bb0115","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.108588","article-title":"Small molecule SARM1 inhibitors recapitulate the SARM1(\u2212\/\u2212) phenotype and allow recovery of a metastable Pool of axons fated to degenerate","volume":"34","author":"Hughes","year":"2021","journal-title":"Cell Rep."},{"key":"10.1016\/j.bioorg.2026.110526_bb0120","doi-asserted-by":"crossref","first-page":"390","DOI":"10.14336\/AD.2023.0516-1","article-title":"SARM1 promotes neurodegeneration and memory impairment in mouse models of Alzheimer\u2019s disease","volume":"15","author":"Miao","year":"2024","journal-title":"Aging Dis."},{"key":"10.1016\/j.bioorg.2026.110526_bb0125","doi-asserted-by":"crossref","DOI":"10.1083\/jcb.201912047","article-title":"SARM1 acts downstream of neuroinflammatory and necroptotic signaling to induce axon degeneration","volume":"219","author":"Ko","year":"2020","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.bioorg.2026.110526_bb0130","doi-asserted-by":"crossref","first-page":"4187","DOI":"10.7150\/thno.49054","article-title":"SARM1 promotes neuroinflammation and inhibits neural regeneration after spinal cord injury through NF-kappaB signaling","volume":"11","author":"Liu","year":"2021","journal-title":"Theranostics"},{"key":"10.1016\/j.bioorg.2026.110526_bb0135","doi-asserted-by":"crossref","DOI":"10.3390\/cells13010054","article-title":"The role of TNF-alpha in Alzheimer\u2019s disease: a narrative review","volume":"13","author":"Plantone","year":"2023","journal-title":"Cells"},{"key":"10.1016\/j.bioorg.2026.110526_bb0140","doi-asserted-by":"crossref","DOI":"10.3389\/fnmol.2022.954541","article-title":"NF-kappaB in neurodegenerative diseases: recent evidence from human genetics","volume":"15","author":"Kaltschmidt","year":"2022","journal-title":"Front. Mol. Neurosci."},{"key":"10.1016\/j.bioorg.2026.110526_bb0145","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.ymthe.2017.12.021","article-title":"Advanced siRNA designs further improve in vivo performance of GalNAc-siRNA conjugates","volume":"26","author":"Foster","year":"2018","journal-title":"Mol. Ther."},{"key":"10.1016\/j.bioorg.2026.110526_bb0150","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s40478-023-01709-4","article-title":"Genetic ablation of Sarm1 attenuates expression and mislocalization of phosphorylated TDP-43 after mouse repetitive traumatic brain injury","volume":"11","author":"Dogan","year":"2023","journal-title":"Acta Neuropathol. Commun."},{"key":"10.1016\/j.bioorg.2026.110526_bb0155","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s12035-012-8375-5","article-title":"A non-transgenic mouse model (icv-STZ mouse) of Alzheimer\u2019s disease: similarities to and differences from the transgenic model (3xTg-AD mouse)","volume":"47","author":"Chen","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.bioorg.2026.110526_bb0160","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1007\/s12035-015-9132-3","article-title":"Intracerebroventricular streptozotocin injections as a model of Alzheimer\u2019s disease: in search of a relevant mechanism","volume":"53","author":"Grieb","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.bioorg.2026.110526_bb0165","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.bioorg.2026.110526_bb0170","doi-asserted-by":"crossref","first-page":"20247","DOI":"10.1038\/s41598-022-24292-5","article-title":"Performance of the intracerebroventricularly injected streptozotocin Alzheimer\u2019s disease model in a translationally relevant, aged and experienced rat population","volume":"12","author":"Gaspar","year":"2022","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bioorg.2026.110526_bb0175","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2023.1161678","article-title":"Intermittent theta burst stimulation attenuates oxidative stress and reactive astrogliosis in the streptozotocin-induced model of Alzheimer\u2019s disease-like pathology","volume":"15","author":"Stanojevic","year":"2023","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.bioorg.2026.110526_bb0180","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2022.113375","article-title":"Bilateral intracerebroventricular injection of streptozotocin induces AD-like behavioral impairments and neuropathological features in mice: involved with the fundamental role of neuroinflammation","volume":"153","author":"Fan","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.bioorg.2026.110526_bb0185","doi-asserted-by":"crossref","DOI":"10.3390\/ijms262210944","article-title":"Temporal progression of recognition memory impairment, astrogliosis, and cholinergic dysfunction in the streptozotocin rat model of sporadic Alzheimer\u2019s disease","volume":"26","author":"Nino-Rivero","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.bioorg.2026.110526_bb0190","doi-asserted-by":"crossref","first-page":"713","DOI":"10.3233\/JAD-221027","article-title":"Sarm1 regulates circadian rhythm disorder in Alzheimer\u2019s disease in mice","volume":"92","author":"Wang","year":"2023","journal-title":"J. Alzheimer\u2019s Dis"}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S004520682601062X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S004520682601062X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:23:46Z","timestamp":1791260626000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S004520682601062X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":38,"alternative-id":["S004520682601062X"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2026.110526","relation":{},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Lipid-conjugated siRNA targeting SARM1 enables CNS silencing and mitigates alzheimer-like phenotypes","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2026.110526","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"110526"}}