{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:19:53Z","timestamp":1792113593305,"version":"4.4.0"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2019\/33\/B\/NZ4\/00587"],"award-info":[{"award-number":["2019\/33\/B\/NZ4\/00587"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Brain"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Brain-derived neurotrophic factor (BDNF) is known for its potent prosurvival effect. Despite successfully replicating this effect in various clinical and pre-clinical models, the complete characterization of the molecular mechanisms underlying its neuroprotective action remains incomplete. Emerging research suggests a vital role for A-kinase anchoring proteins (AKAPs) as central nodal points orchestrating BDNF-dependent signaling. Among the over 50 identified AKAPs, AKAP6 has recently gained special attention due to its involvement in the neurotrophin-mediated survival of injured retinal ganglion cells (RGCs). However, the mechanisms by which AKAP6 responds to pro-survival BDNF signaling remain unknown. In this study, we shown that AKAP6 plays a crucial role in regulating BDNF-mediated NFAT transcriptional activity in neuronal survival by anchoring protein phosphatase calcineurin (CaN) and nuclear factor of activated T cells (NFATc4). Furthermore, we demonstrate that disrupting the anchoring of CaN diminishes the pro-survival effect of BDNF. Lastly, through experiments with NFATc4\u2212\/\u2212 mice, we provide evidence that NFATc4 acts downstream to BDNF\u2019s neuroprotection in vivo. These findings could offer valuable insights for developing neuroprotective strategies aimed at preserving injured neurons from degeneration and promoting their regeneration.<\/jats:p>","DOI":"10.1186\/s13041-024-01157-8","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T15:39:12Z","timestamp":1732289952000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["AKAP6 controls NFATc4 activity for BDNF-mediated neuroprotection"],"prefix":"10.1186","volume":"17","author":[{"given":"Joanna","family":"Mackiewicz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Tomczak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malwina","family":"Lisek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7654-9011","authenticated-orcid":false,"given":"Tomasz","family":"Boczek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"key":"1157_CR1","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1146\/annurev.neuro.23.1.579","volume":"23","author":"JL Goldberg","year":"2000","unstructured":"Goldberg JL, Barres BA. The relationship between neuronal survival and regeneration. Annu Rev Neurosci. 2000;23:579\u2013612.","journal-title":"Annu Rev Neurosci"},{"issue":"3","key":"1157_CR2","doi-asserted-by":"publisher","first-page":"545","DOI":"10.3390\/ijms18030545","volume":"18","author":"SD Chen","year":"2017","unstructured":"Chen SD, Wu CL, Hwang WC, Yang DI. More insight into BDNF against neurodegeneration: anti-apoptosis, anti-oxidation, and suppression of autophagy. Int J Mol Sci. 2017;18(3):545.","journal-title":"Int J Mol Sci"},{"issue":"12","key":"1157_CR3","doi-asserted-by":"publisher","first-page":"1880","DOI":"10.1016\/j.ebiom.2015.10.025","volume":"2","author":"Y Wang","year":"2015","unstructured":"Wang Y, Cameron EG, Li J, Stiles TL, Kritzer MD, Lodhavia R, et al. Muscle A-kinase anchoring protein-\u03b1 is an injury-specific signaling scaffold required for neurotrophic- and cyclic adenosine monophosphate-mediated survival. EBioMedicine. 2015;2(12):1880\u20137.","journal-title":"EBioMedicine"},{"issue":"28","key":"1157_CR4","doi-asserted-by":"publisher","first-page":"5466","DOI":"10.1523\/JNEUROSCI.2752-18.2019","volume":"39","author":"T Boczek","year":"2019","unstructured":"Boczek T, Cameron EG, Yu W, Xia X, Shah SH, Castillo Chabeco B, et al. Regulation of neuronal survival and axon growth by a perinuclear cAMP compartment. J Neurosci. 2019;39(28):5466\u201380.","journal-title":"J Neurosci"},{"issue":"3","key":"1157_CR5","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1097\/FJC.0000000000000206","volume":"65","author":"CL Passariello","year":"2015","unstructured":"Passariello CL, Li J, Dodge-Kafka K, Kapiloff MS. mAKAP-a master scaffold for cardiac remodeling. 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The Institutional Animal Care and Use Committee at Medical University of Lodz approved the study (reference 47\/\u0141B 182\/2020).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate:"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"85"}}