{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:53:11Z","timestamp":1781643191317,"version":"3.54.5"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":67,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012306","name":"Universit\u00e0 degli Studi di Trieste","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012306","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell. Mol. Life Sci."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    In Alzheimer\u2019s disease (AD), brain levels of Brain-derived neurotrophic factor (BDNF) are reduced. BDNF, a neurotrophin involved in neuronal development and plasticity, has a protective role against the cytotoxic effects of A\u03b2, a pathological hallmark of AD. Since therapeutic approaches to increase BDNF levels by supplementing BDNF directly in the nervous system have been ineffective, we explored an alternative strategy: to increase intracellular BDNF levels by using synthetic SINEUP long non-coding RNAs which upregulate protein synthesis without altering mRNA levels. We designed one SINEUP common to all BDNF transcripts (SINEUP-PAN) and one SINEUP complementary to the BDNF 5\u2019exon-I transcript (SINEUP-Ex1), which is downregulated in AD and not expressed in non-neuronal tissues. SINEUPs activity and specificity have been first proven on endogenous targets in different mammalian cell lines \u2013 human neuroblastoma cells, rat neurons and mouse astrocytes. During in vitro development of na\u00efve primary rat hippocampal neurons, SINEUP-Ex1, but not SINEUP-PAN, induced more complex dendritic arborisations at 12 days in vitro (DIV12). In DIV6 neurons, 24\u00a0h incubation with aggregated A\u03b2\n                    <jats:sub>25\u221235<\/jats:sub>\n                    peptide caused neuronal atrophy and both SINEUP-PAN and SINEUP-Ex1 promoted the full rescue of soma size, apical dendrite diameter, and number of dendritic endpoints, but not of the total dendritic length. The protection from the A\u03b2-challenge achieved with the two SINEUPs appear to involve distinct mechanisms, as only SINEUP-PAN was able to increase Map2, a marker of dendritic microtubules which show aberrations in AD. These results support SINEUP as a potential new tool for a gene-therapy in AD and other neurodegenerative diseases.\n                  <\/jats:p>","DOI":"10.1007\/s00018-026-06175-4","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T04:11:03Z","timestamp":1773461463000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long non-coding SINEUP RNA enhancing BDNF translation prevents dendritic atrophy following an A\u03b2-peptide challenge"],"prefix":"10.1007","volume":"83","author":[{"given":"Marta","family":"Atzori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa","family":"Fabbretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana","family":"Ciraci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Zucchelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"Bon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanja","family":"Mika\u0161inovi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Baj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Gustincich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0485-0603","authenticated-orcid":false,"given":"Enrico","family":"Tongiorgi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,14]]},"reference":[{"key":"6175_CR1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.brainresbull.2014.02.004","volume":"103","author":"JN Cochran","year":"2014","unstructured":"Cochran JN, Hall AM, Roberson ED (2014) The dendritic hypothesis for Alzheimer\u2019s disease pathophysiology. Brain Res Bull 103:18\u201328. https:\/\/doi.org\/10.1016\/j.brainresbull.2014.02.004","journal-title":"Brain Res Bull"},{"issue":"7","key":"6175_CR2","doi-asserted-by":"publisher","first-page":"2636","DOI":"10.1523\/JNEUROSCI.4456-09.2010","volume":"30","author":"H-Y Wu","year":"2010","unstructured":"Wu H-Y, Hudry E, Hashimoto T, Kuchibhotla K, Rozkalne A, Fan Z, Spires-Jones T, Xie H, Arbel-Ornath M, Grosskreutz CL, Bacskai BJ, Hyman BT (2010) Amyloid-beta Induces the Morphological Neurodegenerative Triad of Spine Loss, Dendritic Simplification, and Neuritic Dystrophies through Calcineurin Activation. J Neurosci 30(7):2636\u20132649. https:\/\/doi.org\/10.1523\/JNEUROSCI.4456-09.2010","journal-title":"J Neurosci"},{"key":"6175_CR3","doi-asserted-by":"publisher","first-page":"38","DOI":"10.3389\/fnana.2014.00038","volume":"8","author":"M Llorens-Mart\u00edn","year":"2014","unstructured":"Llorens-Mart\u00edn M, Blazquez-Llorca L, Benavides-Piccione R, Rabano A, Hernandez F, Avila J, DeFelipe J (2014) Selective alterations of neurons and circuits related to early memory loss in Alzheimer\u2019s disease. Front Neuroanat 8:38. https:\/\/doi.org\/10.3389\/fnana.2014.00038","journal-title":"Front Neuroanat"},{"issue":"1","key":"6175_CR4","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.mcn.2012.03.005","volume":"50","author":"VA Kulkarni","year":"2012","unstructured":"Kulkarni VA, Firestein BL (2012) The dendritic tree and brain disorders. Mol Cell Neurosci 50(1):10\u201320. https:\/\/doi.org\/10.1016\/j.mcn.2012.03.005","journal-title":"Mol Cell Neurosci"},{"issue":"3","key":"6175_CR5","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.conb.2007.03.013","volume":"17","author":"O Arancio","year":"2007","unstructured":"Arancio O, Chao MV (2007) Neurotrophins, synaptic plasticity and dementia. Curr Opin Neurobiol 17(3):325\u2013330. https:\/\/doi.org\/10.1016\/j.conb.2007.03.013","journal-title":"Curr Opin Neurobiol"},{"issue":"1","key":"6175_CR6","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.brainresrev.2008.07.007","volume":"59","author":"L Tapia-Arancibia","year":"2008","unstructured":"Tapia-Arancibia L, Aliaga E, Silhol M, Arancibia S (2008) New insights into brain BDNF function in normal aging and Alzheimer disease. Brain Res Rev 59(1):201\u2013220. https:\/\/doi.org\/10.1016\/j.brainresrev.2008.07.007","journal-title":"Brain Res Rev"},{"issue":"3","key":"6175_CR7","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/nm.1912","volume":"15","author":"AH Nagahara","year":"2009","unstructured":"Nagahara AH, Merrill DA, Coppola G, Tsukada S, Schroeder BE, Shaked GM, Wang L, Blesch A, Kim A, Conner JM, Rockenstein E, Chao MV, Koo EW, Geschwind D, Masliah E, Chiba AA, Tuszynski MH (2009) Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer\u2019s disease. Nat Med 15(3):331\u2013337. https:\/\/doi.org\/10.1038\/nm.1912","journal-title":"Nat Med"},{"issue":"7","key":"6175_CR8","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1021\/cn500051h","volume":"5","author":"M Prior","year":"2014","unstructured":"Prior M, Chiruta C, Currais A, Goldberg J, Ramsey J, Dargusch R, Maher PA, Schubert D (2014) Back to the Future with Phenotypic Screening. ACS Chem Neurosci 5(7):503\u2013513. https:\/\/doi.org\/10.1021\/cn500051h","journal-title":"ACS Chem Neurosci"},{"issue":"5","key":"6175_CR9","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1046\/j.1471-4159.2002.01029.x","volume":"82","author":"D Garzon","year":"2002","unstructured":"Garzon D, Yu G, Fahnestock M (2002) A new brain-derived neurotrophic factor transcript and decrease in brain-derived neurotrophic factor transcripts 1, 2 and 3 in Alzheimer\u2019s disease parietal cortex. J Neurochem 82(5):1058\u20131064. https:\/\/doi.org\/10.1046\/j.1471-4159.2002.01029.x","journal-title":"J Neurochem"},{"key":"6175_CR10","doi-asserted-by":"publisher","unstructured":"Tanila H (2017) The role of BDNF in Alzheimer\u2019s disease. Neurobiol Dis 97(Pt B) 114\u2013118. https:\/\/doi.org\/10.1016\/j.nbd.2016.05.002","DOI":"10.1016\/j.nbd.2016.05.002"},{"key":"6175_CR11","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.nbd.2017.08.015","volume":"108","author":"MF Iulita","year":"2017","unstructured":"Iulita MF, Bistu\u00e9 Mill\u00f3n MB, Pentz R et al (2017) Differential deregulation of NGF and BDNF neurotrophins in a transgenic rat model of Alzheimer\u2019s disease. Neurobiol Dis 108:307\u2013323. https:\/\/doi.org\/10.1016\/j.nbd.2017.08.015","journal-title":"Neurobiol Dis"},{"key":"6175_CR12","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.freeradbiomed.2017.07.013","volume":"114","author":"XQ Chen","year":"2018","unstructured":"Chen XQ, Sawa M, Mobley WC (2018) Dysregulation of neurotrophin signaling in the pathogenesis of Alzheimer disease and of Alzheimer disease in Down syndrome. Free Radic Biol Med 114:52\u201361. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2017.07.013","journal-title":"Free Radic Biol Med"},{"issue":"11","key":"6175_CR13","doi-asserted-by":"publisher","first-page":"3017","DOI":"10.1523\/JNEUROSCI.4037-06.2007","volume":"27","author":"CS Rex","year":"2007","unstructured":"Rex CS, Lin C-Y, Kram\u00e1r EA, Chen LY, Gall CM, Lynch G (2007) Brain-Derived Neurotrophic Factor Promotes Long-Term Potentiation-Related Cytoskeletal Changes in Adult Hippocampus. J Neurosci 27(11):3017\u20133029. https:\/\/doi.org\/10.1523\/JNEUROSCI.4037-06.2007","journal-title":"J Neurosci"},{"issue":"44","key":"6175_CR14","doi-asserted-by":"publisher","first-page":"9760","DOI":"10.1523\/JNEUROSCI.1427-04.2004","volume":"24","author":"N Takei","year":"2004","unstructured":"Takei N, Inamura N, Kawamura M, Namba H, Hara K, Yonezawa K, Nawa H (2004) Brain-Derived Neurotrophic Factor Induces Mammalian Target of Rapamycin-Dependent Local Activation of Translation Machinery and Protein Synthesis in Neuronal Dendrites. J Neurosci 24(44):9760\u20139769. https:\/\/doi.org\/10.1523\/JNEUROSCI.1427-04.2004","journal-title":"J Neurosci"},{"issue":"3","key":"6175_CR15","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/nrd3366","volume":"10","author":"AH Nagahara","year":"2011","unstructured":"Nagahara AH, Tuszynski MH (2011) Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov 10(3):209\u2013219. https:\/\/doi.org\/10.1038\/nrd3366","journal-title":"Nat Rev Drug Discov"},{"issue":"6","key":"6175_CR16","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/nrn3505","volume":"14","author":"B Lu","year":"2013","unstructured":"Lu B, Nagappan G, Guan X, Nathan PJ, Wren P (2013) BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases. Nat Rev Neurosci 14(6):401\u2013416. https:\/\/doi.org\/10.1038\/nrn3505","journal-title":"Nat Rev Neurosci"},{"issue":"3","key":"6175_CR17","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1007\/s12035-014-8958-4","volume":"52","author":"JH Song","year":"2015","unstructured":"Song JH, Yu JT, Tan L (2015) Brain-Derived Neurotrophic Factor in Alzheimer\u2019s Disease: Risk, Mechanisms, and Therapy. Mol Neurobiol 52(3):1477\u20131493. https:\/\/doi.org\/10.1007\/s12035-014-8958-4","journal-title":"Mol Neurobiol"},{"issue":"1","key":"6175_CR18","doi-asserted-by":"publisher","first-page":"45","DOI":"10.2174\/1566523218666180307161059","volume":"18","author":"A Mohammadi","year":"2018","unstructured":"Mohammadi A, Amooeian VG, Rashidi E (2018) Dysfunction in Brain-Derived Neurotrophic Factor Signaling Pathway and Susceptibility to Schizophrenia, Parkinson\u2019s and Alzheimer\u2019s Diseases. Curr Gene Ther 18(1):45\u201363. https:\/\/doi.org\/10.2174\/1566523218666180307161059","journal-title":"Curr Gene Ther"},{"issue":"5","key":"6175_CR19","doi-asserted-by":"publisher","first-page":"503","DOI":"10.2174\/156720507783018217","volume":"4","author":"FM Longo","year":"2007","unstructured":"Longo FM, Yang T, Knowles JK, Xie Y, Moore LA, Massa SM (2007) Small molecule neurotrophin receptor ligands: Novel strategies for targeting Alzheimer\u2019s disease mechanisms. Curr Alzheimer Res 4(5):503\u2013506. https:\/\/doi.org\/10.2174\/156720507783018217","journal-title":"Curr Alzheimer Res"},{"issue":"1","key":"6175_CR20","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3390\/pharmaceutics5010127","volume":"5","author":"C G\u00e9ral","year":"2013","unstructured":"G\u00e9ral C, Angelova A, Lesieur S (2013) From molecular to nanotechnology strategies for delivery of neurotrophins: emphasis on brain-derived neurotrophic factor (BDNF). Pharmaceutics 5(1):127\u2013167. https:\/\/doi.org\/10.3390\/pharmaceutics5010127","journal-title":"Pharmaceutics"},{"key":"6175_CR21","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/1471-2202-5-19","volume":"5","author":"G Heinrich","year":"2004","unstructured":"Heinrich G, Pagtakhan CJ (2004) Both 5\u2019 and 3\u2019 flanks regulate Zebrafish brain-derived neurotrophic factor gene expression. BMC Neurosci 5:19. https:\/\/doi.org\/10.1186\/1471-2202-5-19","journal-title":"BMC Neurosci"},{"issue":"3","key":"6175_CR22","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1002\/jnr.21139","volume":"85","author":"T Aid","year":"2007","unstructured":"Aid T, Kazantseva A, Piirsoo M, Palm K, Timmusk T (2007) Mouse and rat BDNF gene structure and expression revisited. J Neurosci Res 85(3):525\u2013535. https:\/\/doi.org\/10.1002\/jnr.21139","journal-title":"J Neurosci Res"},{"issue":"3","key":"6175_CR23","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.ygeno.2007.05.004","volume":"90","author":"P Pruunsild","year":"2007","unstructured":"Pruunsild P, Kazantseva A, Aid T, Palm K, Timmusk T (2007) Dissecting the human BDNF locus: bidirectional transcription, complex splicing, and multiple promoters. Genomics 90(3):397\u2013406. https:\/\/doi.org\/10.1016\/j.ygeno.2007.05.004","journal-title":"Genomics"},{"issue":"40","key":"6175_CR24","doi-asserted-by":"publisher","first-page":"16813","DOI":"10.1073\/pnas.1014168108","volume":"108","author":"G Baj","year":"2011","unstructured":"Baj G, Leone E, Chao MV, Tongiorgi E (2011) Spatial segregation of BDNF transcripts enables BDNF to differentially shape distinct dendritic compartments. Proc Natl Acad Sci U S A 108(40):16813\u201316818. https:\/\/doi.org\/10.1073\/pnas.1014168108","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"40","key":"6175_CR25","doi-asserted-by":"publisher","first-page":"27702","DOI":"10.1074\/jbc.M114.586719","volume":"289","author":"V Vaghi","year":"2014","unstructured":"Vaghi V, Polacchini A, Baj G, Pinheiro VL, Vicario A, Tongiorgi E (2014) Pharmacological profile of brain-derived neurotrophic factor (BDNF) splice variant translation using a novel drug screening assay: a quantitative code. J Biol Chem 289(40):27702\u201327713. https:\/\/doi.org\/10.1074\/jbc.M114.586719","journal-title":"J Biol Chem"},{"issue":"8","key":"6175_CR26","doi-asserted-by":"publisher","first-page":"1943","DOI":"10.1038\/npp.2015.349","volume":"41","author":"KR Maynard","year":"2015","unstructured":"Maynard KR, Hill JL, Calcaterra NE, Palko ME, Kardian A, Paredes D, Sukumar M, Adler BD, Jimenez DJ, Schloesser RJ, Tessarollo L, Lu B, Martinowich K (2015) Functional role of BDNF production from unique promoters in aggression and serotonin signaling. Neuropsychopharmacology 41(8):1943\u20131955. https:\/\/doi.org\/10.1038\/npp.2015.349","journal-title":"Neuropsychopharmacology"},{"key":"6175_CR27","doi-asserted-by":"publisher","first-page":"174","DOI":"10.3389\/fncel.2015.00174","volume":"9","author":"S Zucchelli","year":"2015","unstructured":"Zucchelli S, Fasolo F, Russo R, Cimatti L, Patrucco L, Takahashi H, Jones MH, Santoro C, Sblattero D, Cotella D, Persichetti F, Carninci P, Gustincich S (2015a) SINEUPs are modular antisense long non-coding RNAs that increase synthesis of target proteins in cells. Front Cell Neurosci 9:174. https:\/\/doi.org\/10.3389\/fncel.2015.00174","journal-title":"Front Cell Neurosci"},{"key":"6175_CR28","doi-asserted-by":"publisher","first-page":"33605","DOI":"10.1038\/srep33605","volume":"6","author":"A Schein","year":"2016","unstructured":"Schein A, Zucchelli S, Kauppinen S, Gustincich S, Carninci P (2016) Identification of antisense long noncoding RNAs that function as SINEUPs in human cells. Sci Rep 6:33605. https:\/\/doi.org\/10.1038\/srep33605","journal-title":"Sci Rep"},{"issue":"8","key":"6175_CR29","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1080\/15476286.2015.1060395","volume":"12","author":"S Zucchelli","year":"2015","unstructured":"Zucchelli S, Cotella D, Takahashi H, Carrieri C, Cimatti L, Fasolo F, Jones MH, Sblattero D, Sanges R, Santoro C, Persichetti F, Carninci P, Gustincich S (2015b) SINEUPs: A new class of natural and synthetic antisense long non-coding RNAs that activate translation. RNA Biol 12(8):771\u2013779. https:\/\/doi.org\/10.1080\/15476286.2015.1060395","journal-title":"RNA Biol"},{"key":"6175_CR30","unstructured":"D\u2019Agostino S, Tettey-Matey A, Volpe M, Pierattini B, D\u2019Agostino M, Sm\u011bl\u00e1 D, Ansaloni F, Broglia L, Lau P, Peruzzo O, Braccia C, Armirotti A, Scarpato M, Damiani D, Ros G, Di Carlo V, Maniscalco F, Bechara E, Tartaglia GG, Carninci P, Santoro C, Persichetti F, Pandolfini L, Simonetti A, Espinoza S, Zucchelli S, Sanges R, Bon C, Gustincich S (in press) Internal Ribosome Entry Sites enhance translation in trans in antisense non-coding SINEUP and circular RNAs. Nucleic Acids Res DOI: Not yet assigned"},{"issue":"7424","key":"6175_CR31","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1038\/nature11508","volume":"491","author":"C Carrieri","year":"2012","unstructured":"Carrieri C, Cimatti L, Biagioli M, Beugnet A, Zucchelli S, Fedele S, Pesce E, Ferrer I, Collavin L, Santoro C, Forrest AR, Carninci P, Biffo S, Stupka E, Gustincich S (2012) Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature 491(7424):454\u2013457. https:\/\/doi.org\/10.1038\/nature11508","journal-title":"Nature"},{"key":"6175_CR32","doi-asserted-by":"publisher","first-page":"114","DOI":"10.3389\/fncel.2015.00114","volume":"9","author":"C Carrieri","year":"2015","unstructured":"Carrieri C, Forrest AR, Santoro C, Persichetti F, Carninci P, Zucchelli S, Gustincich S (2015) Expression analysis of the long non-coding RNA antisense to Uchl1 (AS Uchl1) during dopaminergic cells\u2019 differentiation in vitro and in neurochemical models of Parkinson\u2019s disease. Front Cell Neurosci 9:114. https:\/\/doi.org\/10.3389\/fncel.2015.00114","journal-title":"Front Cell Neurosci"},{"key":"6175_CR33","doi-asserted-by":"publisher","first-page":"27315","DOI":"10.1038\/srep27315","volume":"6","author":"A Indrieri","year":"2016","unstructured":"Indrieri A, Grimaldi C, Zucchelli S, Tammaro R, Gustincich S, Franco B (2016) Synthetic long non-coding RNAs [SINEUPs] rescue defective gene expression in vivo. Sci Rep 6:27315. https:\/\/doi.org\/10.1038\/srep27315","journal-title":"Sci Rep"},{"issue":"20","key":"6175_CR34","doi-asserted-by":"publisher","first-page":"10728","DOI":"10.1093\/nar\/gkz798","volume":"47","author":"C Bon","year":"2019","unstructured":"Bon C, Luffarelli R, Russo R, Fortuni S, Pierattini B, Santulli C, Fimiani C, Persichetti F, Cotella D, Mallamaci A, Santoro C, Carninci P, Espinoza S, Testi R, Zucchelli S, Cond\u00f2 I, Gustincich S (2019) SINEUP non-coding RNAs rescue defective frataxin expression and activity in a cellular model of Friedreich\u2019s Ataxia. Nucleic Acids Res 47(20):10728\u201310743. https:\/\/doi.org\/10.1093\/nar\/gkz798","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"6175_CR35","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1016\/j.ymthe.2024.12.043","volume":"33","author":"F Di Leva","year":"2025","unstructured":"Di Leva F, Arnoldi M, Santarelli S, Massonot M, Lem\u00e9e MV, Bon C, Pellegrini M, Castellini ME, Zarantonello G, Messina A, Bozzi Y, Bernier R, Zucchelli S, Casarosa S, Dassi E, Ronzitti G, Golzio C, Morandell J, Gustincich S, Espinoza S, Biagioli M (2025) SINEUP RNA rescues molecular phenotypes associated with CHD8 suppression in autism spectrum disorder model systems. Mol Ther 33(3):1180\u20131196. https:\/\/doi.org\/10.1016\/j.ymthe.2024.12.043","journal-title":"Mol Ther"},{"issue":"797","key":"6175_CR36","doi-asserted-by":"publisher","first-page":"eadn8417","DOI":"10.1126\/scitranslmed.adn8417","volume":"17","author":"H Chen","year":"2025","unstructured":"Chen H, LaFlamme CW, Wang YD, Blan AW, Koehler N, Mendonca Moraes R, Olszewski AR, Almanza Fuerte EP, Bonkowski ES, Bajpai R, Lavado A, Pruett-Miller SM, Mefford HC (2025) Patient-derived models of UBA5-associated encephalopathy identify defects in neurodevelopment and highlight potential therapeutic avenues. Sci Transl Med 17(797):eadn8417. https:\/\/doi.org\/10.1126\/scitranslmed.adn8417","journal-title":"Sci Transl Med"},{"issue":"2","key":"6175_CR37","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1016\/j.ymthe.2019.11.016","volume":"28","author":"S Espinoza","year":"2020","unstructured":"Espinoza S, Scarpato M, Damiani D, Manag\u00f2 F, Mereu M, Contestabile A, Peruzzo O, Carninci P, Santoro C, Papaleo F, Mingozzi F, Ronzitti G, Zucchelli S, Gustincich S (2020) SINEUP Non-coding RNA Targeting GDNF Rescues Motor Deficits and Neurodegeneration in a Mouse Model of Parkinson\u2019s Disease. Mol Ther 28(2):642\u2013652. https:\/\/doi.org\/10.1016\/j.ymthe.2019.11.016","journal-title":"Mol Ther"},{"issue":"38","key":"6175_CR38","doi-asserted-by":"publisher","first-page":"16481","DOI":"10.1073\/pnas.0902833106","volume":"106","author":"C Chiaruttini","year":"2009","unstructured":"Chiaruttini C, Vicario A, Li Z et al (2009) Dendritic trafficking of BDNF mRNA is mediated by translin and blocked by the G196A (Val66Met) mutation. Proc Natl Acad Sci U S A 106(38):16481\u201316486. https:\/\/doi.org\/10.1073\/pnas.0902833106","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"6175_CR39","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/s12038-009-0033-3","volume":"34","author":"L Millucci","year":"2009","unstructured":"Millucci L, Raggiaschi R, Franceschini D, Terstappen G, Santucci A (2009) Rapid aggregation and assembly in aqueous solution of A beta (25\u201335) peptide. J Biosci 34(2):293\u2013303. https:\/\/doi.org\/10.1007\/s12038-009-0033-3","journal-title":"J Biosci"},{"key":"6175_CR40","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8603-3_7","volume-title":"Brain-Derived Neurotrophic Factor (BDNF). Neuromethods vol 143","author":"S Doneg\u00e0","year":"2018","unstructured":"Doneg\u00e0 S, Tongiorgi E (2018) Detecting BDNF Protein Forms by ELISA, Western Blot, and Immunofluorescence. In: Duarte C, Tongiorgi E (eds) Brain-Derived Neurotrophic Factor (BDNF). Neuromethods vol 143. Humana, New York, NY. DOI. https:\/\/doi.org\/10.1007\/978-1-4939-8603-3_7"},{"key":"6175_CR41","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/1471-2202-12-100","volume":"12","author":"L Dehmelt","year":"2011","unstructured":"Dehmelt L, Poplawski G, Hwang E, Halpain S (2011) NeuriteQuant: an open source toolkit for high content screens of neuronal morphogenesis. BMC Neurosci 12:100. https:\/\/doi.org\/10.1186\/1471-2202-12-100","journal-title":"BMC Neurosci"},{"issue":"Pt 1","key":"6175_CR42","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1242\/jcs.033316","volume":"122","author":"G Baj","year":"2009","unstructured":"Baj G, Tongiorgi E (2009) BDNF splice variants from the second promoter cluster support cell survival of differentiated neuroblastoma upon cytotoxic stress. J Cell Sci 122(Pt 1):36\u201343. https:\/\/doi.org\/10.1242\/jcs.033316","journal-title":"J Cell Sci"},{"issue":"7","key":"6175_CR43","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1242\/bio.018168","volume":"5","author":"A Polacchini","year":"2016","unstructured":"Polacchini A, Albani C, Baj G, Colliva A, Carpinelli P, Tongiorgi E (2016) Combined cisplatin and aurora inhibitor treatment increase neuroblastoma cell death but surviving cells overproduce BDNF. Biol Open 5(7):899\u2013907. https:\/\/doi.org\/10.1242\/bio.018168","journal-title":"Biol Open"},{"key":"6175_CR44","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3389\/fncel.2014.00018","volume":"8","author":"G Baj","year":"2014","unstructured":"Baj G, Patrizio A, Montalbano A, Sciancalepore M, Tongiorgi E (2014) Developmental and maintenance defects in Rett syndrome neurons identified by a new mouse staging system in vitro. Front Cell Neurosci 8:18. https:\/\/doi.org\/10.3389\/fncel.2014.00018","journal-title":"Front Cell Neurosci"},{"issue":"1","key":"6175_CR45","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1038\/s41598-020-59298-4","volume":"10","author":"E Nerli","year":"2020","unstructured":"Nerli E, Roggero OM, Baj G, Tongiorgi E (2020) In vitro modeling of dendritic atrophy in Rett syndrome: determinants for phenotypic drug screening in neurodevelopmental disorders. Sci Rep 10(1):2491. https:\/\/doi.org\/10.1038\/s41598-020-59298-4","journal-title":"Sci Rep"},{"key":"6175_CR46","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.brainres.2007.01.071","volume":"1143","author":"R Resende","year":"2007","unstructured":"Resende R, Pereira C, Agostinho P, Vieira AP, Malva JO, Oliveira CR (2007) Susceptibility of hippocampal neurons to Abeta peptide toxicity is associated with perturbation of Ca2\u2009+\u2009homeostasis. Brain Res 1143:11\u201321. https:\/\/doi.org\/10.1016\/j.brainres.2007.01.071","journal-title":"Brain Res"},{"issue":"3","key":"6175_CR47","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1002\/jnr.10396","volume":"70","author":"T Kubo","year":"2002","unstructured":"Kubo T, Nishimura S, Kumagae Y, Kaneko I (2002) In vivo conversion of racemized beta-amyloid ([D-Ser 26]A beta 1\u201340) to truncated and toxic fragments ([D-Ser 26]A beta 25\u201335\/40) and fragment presence in the brains of Alzheimer\u2019s patients. J Neurosci Res 70(3):474\u2013483. https:\/\/doi.org\/10.1002\/jnr.10396","journal-title":"J Neurosci Res"},{"issue":"6","key":"6175_CR48","doi-asserted-by":"publisher","first-page":"e99184","DOI":"10.1371\/journal.pone.0099184","volume":"9","author":"GM Gomes","year":"2014","unstructured":"Gomes GM, Dalmolin GD, B\u00e4r J, Karpova A, Mello CF, Kreutz MR, Rubin MA (2014) Inhibition of the polyamine system counteracts \u03b2-amyloid peptide-induced memory impairment in mice: involvement of extrasynaptic NMDA receptors. PLoS ONE 9(6):e99184. https:\/\/doi.org\/10.1371\/journal.pone.0099184","journal-title":"PLoS ONE"},{"issue":"36","key":"6175_CR49","doi-asserted-by":"publisher","first-page":"11938","DOI":"10.1523\/JNEUROSCI.2357-10.2010","volume":"30","author":"H Zempel","year":"2010","unstructured":"Zempel H, Thies E, Mandelkow E, Mandelkow EM (2010) Abeta oligomers cause localized Ca2\u2009+\u2009elevation, missorting of endogenous Tau into dendrites, Tau phosphorylation, and destruction of microtubules and spines. J Neurosci 30(36):11938\u201311950. https:\/\/doi.org\/10.1523\/JNEUROSCI.2357-10.2010","journal-title":"J Neurosci"},{"key":"6175_CR50","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s13024-015-0058-z","volume":"10","author":"N Golovyashkina","year":"2015","unstructured":"Golovyashkina N, Penazzi L, Ballatore C, Smith AB 3rd, Bakota L, Brandt R (2015) Region-specific dendritic simplification induced by A\u03b2, mediated by tau via dysregulation of microtubule dynamics: a mechanistic distinct event from other neurodegenerative processes. Mol Neurodegener 10:60. https:\/\/doi.org\/10.1186\/s13024-015-0058-z","journal-title":"Mol Neurodegener"},{"issue":"1","key":"6175_CR51","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.neuron.2018.06.003","volume":"99","author":"A Ittner","year":"2018","unstructured":"Ittner A, Ittner LM (2018) Dendritic Tau in Alzheimer\u2019s Disease. Neuron 99(1):13\u201327. https:\/\/doi.org\/10.1016\/j.neuron.2018.06.003","journal-title":"Neuron"},{"issue":"3","key":"6175_CR52","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.gpb.2016.12.005","volume":"15","author":"IM Dykes","year":"2017","unstructured":"Dykes IM, Emanueli C (2017) Transcriptional and Post-transcriptional Gene Regulation by Long Non-coding RNA. Genomics Proteom Bioinf 15(3):177\u2013186. https:\/\/doi.org\/10.1016\/j.gpb.2016.12.005","journal-title":"Genomics Proteom Bioinf"},{"issue":"6","key":"6175_CR53","doi-asserted-by":"publisher","first-page":"595","DOI":"10.15252\/emmm.201606210","volume":"8","author":"DJ Selkoe","year":"2016","unstructured":"Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer\u2019s disease at 25 years. EMBO Mol Med 8(6):595\u2013608. https:\/\/doi.org\/10.15252\/emmm.201606210","journal-title":"EMBO Mol Med"},{"issue":"4","key":"6175_CR54","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/alzrt272","volume":"6","author":"WF Goure","year":"2014","unstructured":"Goure WF, Krafft GA, Jerecic J, Hefti F (2014) Targeting the proper amyloid-beta neuronal toxins: a path forward for Alzheimer\u2019s disease immunotherapeutics. Alzheimers Res Ther 6(4):42. https:\/\/doi.org\/10.1186\/alzrt272","journal-title":"Alzheimers Res Ther"},{"issue":"2","key":"6175_CR55","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s11064-008-9778-6","volume":"34","author":"RL Frozza","year":"2009","unstructured":"Frozza RL, Horn AP, Hoppe JB, Sim\u00e3o F, Gerhardt D, Comiran RA, Salbego CG (2009) A comparative study of beta-amyloid peptides Abeta1-42 and Abeta25-35 toxicity in organotypic hippocampal slice cultures. Neurochem Res 34(2):295\u2013303. https:\/\/doi.org\/10.1007\/s11064-008-9778-6","journal-title":"Neurochem Res"},{"issue":"2","key":"6175_CR56","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.ymeth.2003.11.009","volume":"33","author":"B Dalby","year":"2004","unstructured":"Dalby B, Cates S, Harris A et al (2004) Advanced transfection with Lipofectamine 2000 reagent: primary neurons, siRNA, and high-throughput applications. Methods 33(2):95\u2013103. https:\/\/doi.org\/10.1016\/j.ymeth.2003.11.009","journal-title":"Methods"},{"issue":"2","key":"6175_CR57","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1101\/lm.54603","volume":"10","author":"B Lu","year":"2003","unstructured":"Lu B (2003) BDNF and activity-dependent synaptic modulation. Learn Mem 10(2):86\u201398. https:\/\/doi.org\/10.1101\/lm.54603","journal-title":"Learn Mem"},{"issue":"4","key":"6175_CR58","doi-asserted-by":"publisher","first-page":"5399","DOI":"10.3892\/mmr.2015.4104","volume":"12","author":"M Su","year":"2015","unstructured":"Su M, Hong J, Zhao Y, Liu S, Xue X (2015) MeCP2 controls hippocampal brain-derived neurotrophic factor expression via homeostatic interactions with microRNA 132 in rats with depression. Mol Med Rep 12(4):5399\u20135406. https:\/\/doi.org\/10.3892\/mmr.2015.4104","journal-title":"Mol Med Rep"},{"issue":"40","key":"6175_CR59","doi-asserted-by":"publisher","first-page":"9171","DOI":"10.1523\/JNEUROSCI.3040-05.2005","volume":"25","author":"Q Ding","year":"2005","unstructured":"Ding Q, Markesbery WR, Chen Q, Li F, Keller JN (2005) Ribosome dysfunction is an early event in Alzheimer\u2019s disease. J Neurosci 25(40):9171\u20139175. https:\/\/doi.org\/10.1523\/JNEUROSCI.3040-05.2005","journal-title":"J Neurosci"},{"issue":"5","key":"6175_CR60","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1111\/bpa.12335","volume":"26","author":"K Hernandez-Ortega","year":"2016","unstructured":"Hernandez-Ortega K, Garcia-Esparcia P, Gil L, Lucas JJ, Ferrer I (2016) Altered machinery of protein synthesis in Alzheimer\u2019s: from the nucleolus to the ribosome. Brain Pathol 26(5):593\u2013605. https:\/\/doi.org\/10.1111\/bpa.12335","journal-title":"Brain Pathol"},{"issue":"5","key":"6175_CR61","doi-asserted-by":"publisher","first-page":"e12801","DOI":"10.1111\/acel.12801","volume":"17","author":"J Cheng","year":"2018","unstructured":"Cheng J, North BJ, Zhang T, Dai X, Tao K, Guo J, Wei W (2018) The emerging roles of protein homeostasis-governing pathways in Alzheimer\u2019s disease. Aging Cell 17(5):e12801. https:\/\/doi.org\/10.1111\/acel.12801","journal-title":"Aging Cell"},{"issue":"9","key":"6175_CR62","doi-asserted-by":"publisher","first-page":"6017","DOI":"10.1007\/s12035-019-1491-8","volume":"56","author":"M Mirzaei","year":"2019","unstructured":"Mirzaei M, Pushpitha K, Deng L, Chitranshi N, Gupta V, Rajput R, Mangani AB, Dheer Y, Godinez A, McKay MJ, Kamath K, Pascovici D, Wu JX, Salekdeh GH, Karl T, Haynes PA, Graham SL, Gupta VK (2019) Upregulation of Proteolytic Pathways and Altered Protein Biosynthesis Underlie Retinal Pathology in a Mouse Model of Alzheimer\u2019s Disease. Mol Neurobiol 56(9):6017\u20136034. https:\/\/doi.org\/10.1007\/s12035-019-1491-8","journal-title":"Mol Neurobiol"},{"issue":"4","key":"6175_CR63","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.neures.2008.04.013","volume":"61","author":"E Tongiorgi","year":"2008","unstructured":"Tongiorgi E (2008) Activity-dependent expression of brain-derived neurotrophic factor in dendrites: facts and open questions. Neurosci Res 61(4):335\u2013346. https:\/\/doi.org\/10.1016\/j.neures.2008.04.013","journal-title":"Neurosci Res"},{"issue":"30","key":"6175_CR64","doi-asserted-by":"publisher","first-page":"6842","DOI":"10.1523\/JNEUROSCI.1341-04.2004","volume":"24","author":"E Tongiorgi","year":"2004","unstructured":"Tongiorgi E, Armellin M, Giulianini PG et al (2004) Brain-derived neurotrophic factor mRNA and protein are targeted to discrete dendritic laminas by events that trigger epileptogenesis. J Neurosci 24(30):6842\u20136852. https:\/\/doi.org\/10.1523\/JNEUROSCI.1341-04.2004","journal-title":"J Neurosci"},{"issue":"3","key":"6175_CR65","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.mcn.2004.11.010","volume":"28","author":"PP Pattabiraman","year":"2005","unstructured":"Pattabiraman PP, Tropea D, Chiaruttini C, Tongiorgi E, Cattaneo A, Domenici L (2005) Neuronal activity regulates the developmental expression and subcellular localization of cortical BDNF mRNA isoforms in vivo. Mol Cell Neurosci 28(3):556\u2013570. https:\/\/doi.org\/10.1016\/j.mcn.2004.11.010","journal-title":"Mol Cell Neurosci"},{"issue":"1","key":"6175_CR66","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.mcn.2007.08.011","volume":"37","author":"C Chiaruttini","year":"2008","unstructured":"Chiaruttini C, Sonego M, Baj G, Simonato M, Tongiorgi E (2008) BDNF mRNA splice variants display activity-dependent targeting to distinct hippocampal laminae. Mol Cell Neurosci 37(1):11\u201319. https:\/\/doi.org\/10.1016\/j.mcn.2007.08.011","journal-title":"Mol Cell Neurosci"},{"issue":"5","key":"6175_CR67","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1002\/hipo.22100","volume":"23","author":"G Baj","year":"2013","unstructured":"Baj G, Del Turco D, Schlaudraff J, Torelli L, Deller T, Tongiorgi E (2013) Regulation of the spatial code for BDNF mRNA isoforms in the rat hippocampus following pilocarpine-treatment: a systematic analysis using laser microdissection and quantitative real-time PCR. Hippocampus 23(5):413\u2013423. https:\/\/doi.org\/10.1002\/hipo.22100","journal-title":"Hippocampus"},{"issue":"8","key":"6175_CR68","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.1038\/npp.2016.29","volume":"41","author":"M Song","year":"2016","unstructured":"Song M, Lee FS (2016) New Insights into the Biology of the BDNF Transcriptional \u2018Code\u2019. Neuropsychopharmacology 41(8):1941\u20131942. https:\/\/doi.org\/10.1038\/npp.2016.29","journal-title":"Neuropsychopharmacology"},{"issue":"6","key":"6175_CR69","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1111\/jnc.13124","volume":"134","author":"I Koppel","year":"2015","unstructured":"Koppel I, Tuvikene J, Lekk I, Timmusk T (2015) Efficient use of a translation start codon in BDNF exon I. J Neurochem 134(6):1015\u20131025. https:\/\/doi.org\/10.1111\/jnc.13124","journal-title":"J Neurochem"}],"container-title":["Cellular and Molecular Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00018-026-06175-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00018-026-06175-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00018-026-06175-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:04:04Z","timestamp":1781640244000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00018-026-06175-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,14]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["6175"],"URL":"https:\/\/doi.org\/10.1007\/s00018-026-06175-4","relation":{},"ISSN":["1420-9071"],"issn-type":[{"value":"1420-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,14]]},"assertion":[{"value":"11 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 March 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"EF, ET, VC and SG and are co-inventor in the patent ITALIA N. 102023000026952 with international extension PCT\/IB2024\/062610, covering the use of SINEUPs to increase BDNF expression for any commercial and therapeutic purposes, including BDNF industrial protein production and gene-therapy use. SG is co-inventor in a patent on the use of SINEUPs for therapy.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"214"}}