{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:58:28Z","timestamp":1792119508940,"version":"4.4.0"},"reference-count":330,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Medicine and Pharmacy Carol Davila"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The brain-derived neurotrophic factor (BDNF) has become one of the cornerstones of neuropathology, influencing synaptic plasticity, cognitive resilience, and neuronal survival. Apart from its molecular biology, BDNF is a powerful target for transformative benefit in precision medicine, leading to innovative therapeutic approaches for neurodegenerative and psychiatric diseases like Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), major depressive disorder (MDD), and post-traumatic stress disorder (PTSD). Nevertheless, clinical applicability is obstructed by hurdles in delivery, patient-specific diversity, and pleiotropic signaling. Here, we summarize findings in BDNF research, including its regulatory pathways and diagnostic\/prognostic biomarkers and integrative therapeutic approaches. We describe innovative delivery systems, such as lipid nanoparticle-based mRNA therapies and CRISPR-dCas9-based epigenetic editing that bypass obstacles such as BBB (blood\u2013brain barrier) and enzymatic degradation. The recent implementation of multiplex panels combining BDNF biodynamic indicators with tau and amyloid-\u03b2 signaling markers showcases novel levels of specificity for both early detection and potential therapeutic monitoring. Humanized preclinical models like iPSC-derived neurons and organoids point to the key role of BDNF in neurodeveloping and neurodegenerative processes, paralleling advances in bridging preclinical observation and clinical environments. Moreover, novel therapeutic tools delivering TrkB activators or the implementation of AI-based dynamic care platforms enable tailored and scalable treatments. This review also aims to extend a framework used in the understanding of BDNF\u2019s relevance to traditional neurodegenerative models by situating more recent work detailing BDNF\u2019s actions in ischemic tissues and the gut\u2013brain axis in the context of systemic health. Finally, we outline a roadmap for the incorporation of BDNF-centered therapies into worldwide healthcare, highlighting ethical issues, equity, and interdisciplinary decomposition. The therapeutic potential of BDNF heralds a new era in neuroscience and medicine, revolutionizing brain health and paving the way for the advancement of precision medicine.<\/jats:p>","DOI":"10.3390\/ijms26094271","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T07:00:21Z","timestamp":1745996421000},"page":"4271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":162,"title":["From Synaptic Plasticity to Neurodegeneration: BDNF as a Transformative Target in Medicine"],"prefix":"10.3390","volume":"26","author":[{"given":"Corneliu","family":"Toader","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Vascular Neurosurgery, National Institute of Neurology and Neurovascular Diseases, 077160 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matei","family":"Serban","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Vascular Neurosurgery, National Institute of Neurology and Neurovascular Diseases, 077160 Bucharest, Romania"},{"name":"Puls Med Association, 051885 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Octavian","family":"Munteanu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razvan-Adrian","family":"Covache-Busuioc","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Vascular Neurosurgery, National Institute of Neurology and Neurovascular Diseases, 077160 Bucharest, Romania"},{"name":"Puls Med Association, 051885 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaly","family":"Enyedi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru Vlad","family":"Ciurea","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Neurosurgery Department, Sanador Clinical Hospital, 010991 Bucharest, Romania"},{"name":"Medical Section, Romanian Academy, 010071 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calin Petru","family":"Tataru","sequence":"additional","affiliation":[{"name":"Department of Opthamology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"You, S., Ma, Z., Zhang, P., Xu, W., Zhan, C., Sang, N., Xu, J., Wang, F., and Zhang, J. 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