{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T21:24:38Z","timestamp":1774992278283,"version":"3.50.1"},"reference-count":256,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T00:00:00Z","timestamp":1658275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS110398"],"award-info":[{"award-number":["NS110398"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS105826"],"award-info":[{"award-number":["NS105826"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brain-derived neurotrophic factor is an extensively studied neurotrophin implicated in the pathology of multiple neurodegenerative and psychiatric disorders including, but not limited to, Parkinson\u2019s disease, Alzheimer\u2019s disease, Huntington\u2019s disease, traumatic brain injury, major de-pressive disorder, and schizophrenia. Here we provide a brief summary of current knowledge on the role of BDNF and the common human single nucleotide polymorphism, rs6265, in driving the pathogenesis and rehabilitation in these disorders, as well as the status of BDNF-targeted therapies. A common trend has emerged correlating low BDNF levels, either detected within the central nervous system or peripherally, to disease states, suggesting that BDNF replacement therapies may hold clinical promise. In addition, we introduce evidence for a distinct role of the BDNF pro-peptide as a biologically active ligand and the need for continuing studies on its neurological function outside of that as a molecular chaperone. Finally, we highlight the latest research describing the role of rs6265 expression in mechanisms of neurodegeneration as well as paradoxical advances in the understanding of this genetic variant in neuroregeneration. All of this is discussed in the context of personalized medicine, acknowledging there is no \u201cone size fits all\u201d therapy for neurodegenerative or psychiatric disorders and that continued study of the multiple BDNF isoforms and genetic variants represents an avenue for discovery ripe with therapeutic potential.<\/jats:p>","DOI":"10.3390\/ijms23148011","type":"journal-article","created":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T11:22:24Z","timestamp":1658316144000},"page":"8011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["New Frontiers in Neurodegeneration and Regeneration Associated with Brain-Derived Neurotrophic Factor and the rs6265 Single Nucleotide Polymorphism"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3972-2161","authenticated-orcid":false,"given":"Carlye A.","family":"Szarowicz","sequence":"first","affiliation":[{"name":"Department of Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA"},{"name":"Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathy","family":"Steece-Collier","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret E.","family":"Caulfield","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"306","DOI":"10.17712\/nsj.2016.4.20160080","article-title":"Mechanisms and regulation of neurotrophin synthesis and secretion","volume":"21","year":"2016","journal-title":"Neurosciences"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/jez.1401160206","article-title":"Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo","volume":"116","author":"Hamburger","year":"1951","journal-title":"J. Exp. Zool."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/jez.1401230203","article-title":"A diffusible agent of mouse sarcoma, producing hyperplasia of sympathetic ganglia and hyperneurotization of viscera in the chick embryo","volume":"123","author":"Hamburger","year":"1953","journal-title":"J. Exp. Zool."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1002\/j.1460-2075.1982.tb01207.x","article-title":"Purification of a new neurotrophic factor from mammalian brain","volume":"1","author":"Barde","year":"1982","journal-title":"EMBO J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/341149a0","article-title":"Molecular cloning and expression of brain-derived neurotrophic factor","volume":"341","author":"Leibrock","year":"1989","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s10571-017-0510-4","article-title":"BDNF: A Key Factor with Multipotent Impact on Brain Signaling and Synaptic Plasticity","volume":"38","author":"Lietzau","year":"2018","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"254","DOI":"10.3389\/fncel.2014.00254","article-title":"BDNF signaling and survival of striatal neurons","volume":"8","author":"Baydyuk","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00441-020-03253-2","article-title":"The physiology of regulated BDNF release","volume":"382","author":"Brigadski","year":"2020","journal-title":"Cell Tissue Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s00441-020-03226-5","article-title":"BDNF signaling during the lifetime of dendritic spines","volume":"382","author":"Zagrebelsky","year":"2020","journal-title":"Cell Tissue Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nrn3379","article-title":"Neurotrophin regulation of neural circuit development and function","volume":"14","author":"Park","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1002\/cm.21312","article-title":"Cellular and molecular mechanisms regulating neuronal growth by brain-derived neurotrophic factor","volume":"73","author":"Gonzalez","year":"2016","journal-title":"Cytoskeleton"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s00424-017-1964-4","article-title":"Neurobiology of local and intercellular BDNF signaling","volume":"469","author":"Sasi","year":"2017","journal-title":"Pflugers Arch."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1089\/ten.tea.2017.0462","article-title":"Effect of Brain-Derived Neurotrophic Factor on the Neurogenesis and Osteogenesis in Bone Engineering","volume":"24","author":"Liu","year":"2018","journal-title":"Tissue Eng. Part A"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.14336\/AD.2020.0310","article-title":"Influence of BDNF genetic polymorphisms in the pathophysiology of aging-related diseases","volume":"11","author":"Vargas","year":"2020","journal-title":"Aging Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/jnr.21139","article-title":"Mouse and rat BDNF gene structure and expression revisited","volume":"85","author":"Aid","year":"2007","journal-title":"J. Neurosci. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e958","DOI":"10.1038\/tp.2016.214","article-title":"The human BDNF gene: Peripheral gene expression and protein levels as biomarkers for psychiatric disorders","volume":"6","author":"Cattaneo","year":"2016","journal-title":"Transl. Psychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"27702","DOI":"10.1074\/jbc.M114.586719","article-title":"Pharmacological profile of brain-derived neurotrophic factor (BDNF) splice variant translation using a novel drug screening assay b","volume":"289","author":"Vaghi","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1177\/1073858418810142","article-title":"Brain-Derived Neurotrophic Factor (BDNF): Novel Insights into Regulation and Genetic Variation","volume":"25","author":"Notaras","year":"2019","journal-title":"Neuroscientist"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/dneu.20774","article-title":"Brain-derived neurotrophic factor and the development of structural neuronal connectivity","volume":"70","author":"Kidane","year":"2010","journal-title":"Dev. Neurobiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"16481","DOI":"10.1073\/pnas.0902833106","article-title":"Dendritic trafficking of BDNF mRNA is mediated by translin and blocked by the G196A (Val66Met) mutation","volume":"106","author":"Chiaruttini","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.ygeno.2007.05.004","article-title":"Dissecting the human BDNF locus: Bidirectional transcription, complex splicing, and multiple promoters","volume":"90","author":"Pruunsild","year":"2007","journal-title":"Genomics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16003","DOI":"10.1038\/npjscilearn.2016.3","article-title":"Extracellular and intracellular cleavages of proBDNF required at two distinct stages of late-phase LTP","volume":"1","author":"Pang","year":"2016","journal-title":"NPJ Sci. Learn."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1126\/science.1065057","article-title":"Regulation of cell survival by secreted proneurotrophins","volume":"294","author":"Lee","year":"2001","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1126\/science.1100135","article-title":"Cleavage of proBDNF by tPA\/plasmin is essential for long-term hippocampal plasticity","volume":"306","author":"Pang","year":"2004","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12963","DOI":"10.1523\/JNEUROSCI.3118-11.2011","article-title":"Matrix metalloproteinase-9 contributes to kindled seizure development in pentylenetetrazole-treated mice by converting pro-BDNF to mature BDNF in the hippocampus","volume":"31","author":"Mizoguchi","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"522","DOI":"10.3389\/fncel.2018.00522","article-title":"The role of BDNF in peripheral nerve regeneration: Activity-dependent treatments and Val66Met","volume":"12","author":"McGregor","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1038\/ncomms3490","article-title":"Val66Met polymorphism of BDNF alters prodomain structure to induce neuronal growth cone retraction","volume":"4","author":"Anastasia","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.neures.2009.06.004","article-title":"Mechanisms, locations, and kinetics of synaptic BDNF secretion: An update","volume":"65","author":"Brigadski","year":"2009","journal-title":"Neurosci. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"E4475","DOI":"10.1073\/pnas.1511830112","article-title":"Activity-dependent BDNF release via endocytic pathways is regulated by synaptotagmin-6 and complexin","volume":"112","author":"Wong","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","first-page":"1","article-title":"A simple role for BDNF in learning and memory?","volume":"3","author":"Cunha","year":"2010","journal-title":"Front. Mol. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"E3067","DOI":"10.1073\/pnas.1422336112","article-title":"BDNF pro-peptide actions facilitate hippocampal LTD and are altered by the common BDNF polymorphism Val66Met","volume":"112","author":"Mizui","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","first-page":"316","article-title":"Reduced hippocampal volume correlates with executive dysfunctioning in major depression","volume":"31","author":"Frodl","year":"2006","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"105175","DOI":"10.1016\/j.nbd.2020.105175","article-title":"The BDNF Val66Met polymorphism (rs6265) enhances dopamine neuron graft efficacy and side-effect liability in rs6265 knock-in rats","volume":"148","author":"Mercado","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"eaay8477","DOI":"10.1126\/science.1129663","article-title":"Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior","volume":"314","author":"Chen","year":"2006","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0092-8674(03)00035-7","article-title":"The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function","volume":"112","author":"Egan","year":"2003","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6156","DOI":"10.1523\/JNEUROSCI.1017-05.2005","article-title":"Sortilin controls intracellular sorting of brain-derived neurotrophic factor to the regulated secretory pathway","volume":"25","author":"Chen","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.neuron.2004.12.037","article-title":"Sorting and activity-dependent secretion of BDNF require interaction of a specific motif with the sorting receptor carboxypeptidase E","volume":"45","author":"Lou","year":"2005","journal-title":"Neuron"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"29556","DOI":"10.1074\/jbc.M111.219675","article-title":"Neuronal brain-derived neurotrophic factor is synthesized in excess, with levels regulated by sortilin-mediated trafficking and lysosomal degradation","volume":"286","author":"Evans","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"S310","DOI":"10.1038\/sj.bjp.0707509","article-title":"Role of the brain-derived neurotrophic factor at glutamatergic synapses","volume":"153","author":"Carvalho","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Skaper, S.D. (2018). Neurotrophic factors: An overview. Methods in Molecular Biology, Humana Press.","DOI":"10.1007\/978-1-4939-7571-6"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lu, J.J., Yang, M., Sun, Y., and Zhou, X.F. (2014). Synthesis, trafficking and release of BDNF. Handbook of Neurotoxicity, Springer.","DOI":"10.1007\/978-1-4614-5836-4_24"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Adachi, N., Kohara, K., and Tsumoto, T. (2005). Difference in trafficking of brain-derived neurotrophic factor between axons and dendrites of cortical neurons, revealed by live-cell imaging. BMC Neurosci., 6.","DOI":"10.1186\/1471-2202-6-42"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1083\/jcb.201201038","article-title":"BDNF and its pro-peptide are stored in presynaptic dense core vesicles in brain neurons","volume":"196","author":"Dieni","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1098\/rstb.2006.1894","article-title":"Neurotrophin-regulated signalling pathways","volume":"361","author":"Reichardt","year":"2006","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"721","DOI":"10.4103\/1673-5374.156967","article-title":"The p75 neurotrophin receptor: At the crossroad of neural repair and death","volume":"10","author":"Meeker","year":"2015","journal-title":"Neural Regen. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1080\/08977190410001723308","article-title":"Brain-derived neurotrophic factor","volume":"22","author":"Binder","year":"2004","journal-title":"Growth Factors"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/nrn1078","article-title":"Neurotrophins and their receptors: A convergence point for many signalling pathways","volume":"4","author":"Chao","year":"2003","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5455","DOI":"10.1523\/JNEUROSCI.5123-04.2005","article-title":"ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin","volume":"25","author":"Teng","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6340","DOI":"10.1523\/JNEUROSCI.20-17-06340.2000","article-title":"Neurotrophins induce death of hippocampal neurons via the p75 receptor","volume":"20","author":"Friedman","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s11481-014-9566-9","article-title":"Dynamic Nature of the p75 Neurotrophin Receptor in Response to Injury and Disease","volume":"9","author":"Meeker","year":"2014","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2174\/156720506775697061","article-title":"Dissecting the Diverse Actions of Pro- and Mature Neurotrophins","volume":"3","author":"Hempstead","year":"2006","journal-title":"Curr. Alzheimer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"485","DOI":"10.3389\/fncel.2019.00485","article-title":"The p75 Neurotrophin Receptor Facilitates TrkB Signaling and Function in Rat Hippocampal Neurons","volume":"13","author":"Zanin","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.neubiorev.2018.04.001","article-title":"Beyond good and evil: A putative continuum-sorting hypothesis for the functional role of proBDNF\/BDNF-propeptide\/mBDNF in antidepressant treatment","volume":"90","author":"Diniz","year":"2018","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1146\/annurev.neuro.26.041002.131421","article-title":"Selectivity in neurotrophin signaling: Theme and variations","volume":"26","author":"Segal","year":"2003","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"11300","DOI":"10.1523\/JNEUROSCI.2270-05.2005","article-title":"Control of dendritic arborization by the phosphoinositide-3\u2032-kinase- Akt-mammalian target of rapamycin pathway","volume":"25","author":"Jaworski","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"11288","DOI":"10.1523\/JNEUROSCI.2284-05.2005","article-title":"Regulation of dendritic morphogenesis by Ras-PI3K-Akt-mTOR and Ras-MAPK signaling pathways","volume":"25","author":"Kumar","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S1556-0864(15)31506-9","article-title":"The Ras\/Raf\/MAPK Pathway","volume":"1","author":"Molina","year":"2006","journal-title":"J. Thorac. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1038\/srep03185","article-title":"Involvement of TrkB- and p75MNTR -signaling pathways in two contrasting forms of long-lasting synaptic plasticity","volume":"3","author":"Sakuragi","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nn1510","article-title":"Activation of p75NTR by proBDNF facilitates hippocampal long-term depression","volume":"8","author":"Woo","year":"2005","journal-title":"Nat. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"ra82","DOI":"10.1126\/scisignal.2002060","article-title":"Neuronal growth cone retraction relies on proneurotrophin receptor signaling through rac","volume":"4","author":"Deinhardt","year":"2011","journal-title":"Sci. Signal."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.celrep.2014.03.040","article-title":"ProBDNF Negatively Regulates Neuronal Remodeling, Synaptic Transmission, and Synaptic Plasticity in Hippocampus","volume":"7","author":"Yang","year":"2014","journal-title":"Cell Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1007\/s12035-018-1126-5","article-title":"Early Downregulation of p75 NTR by Genetic and Pharmacological Approaches Delays the Onset of Motor Deficits and Striatal Dysfunction in Huntington\u2019s Disease Mice","volume":"56","author":"Suelves","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e595","DOI":"10.1038\/cddis.2013.116","article-title":"Imbalance of p75NTR\/TrkB protein expression in Huntington\u2019s disease: Implication for neuroprotective therapies","volume":"4","author":"Brito","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.3389\/fneur.2021.680765","article-title":"Serum mBDNF and ProBDNF Expression Levels as Diagnosis Clue for Early Stage Parkinson\u2019s Disease","volume":"12","author":"Yi","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.4103\/1673-5374.211173","article-title":"BDNF pro-peptide: A novel synaptic modulator generated as an N-terminal fragment from the BDNF precursor by proteolytic processing","volume":"12","author":"Mizui","year":"2017","journal-title":"Neural Regen. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.phrs.2015.12.019","article-title":"Neurobiological actions by three distinct subtypes of brain-derived neurotrophic factor: Multi-ligand model of growth factor signaling","volume":"105","author":"Mizui","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Uegaki, K., Kumanogoh, H., Mizui, T., Hirokawa, T., Ishikawa, Y., and Kojima, M. (2017). BDNF binds its pro-peptide with high affinity and the common val66met polymorphism attenuates the interaction. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18051042"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.neuron.2018.05.024","article-title":"The BDNF Val66Met Prodomain Disassembles Dendritic Spines Altering Fear Extinction Circuitry and Behavior","volume":"99","author":"Giza","year":"2018","journal-title":"Neuron"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"637","DOI":"10.3389\/fpsyt.2018.00637","article-title":"Genetic variants of the brain-derived neurotrophic factor and metabolic indices in veterans with posttraumatic stress disorder","volume":"9","author":"Tudor","year":"2018","journal-title":"Front. Psychiatry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e66","DOI":"10.1136\/jmg.2006.044883","article-title":"Genetic variants in brain-derived neurotrophic factor associated with Alzheimer\u2019s disease","volume":"44","author":"Huang","year":"2007","journal-title":"J. Med. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"523","DOI":"10.14336\/AD.2017.0717","article-title":"BDNF polymorphism: A review of its diagnostic and clinical relevance in neurodegenerative disorders","volume":"9","author":"Shen","year":"2018","journal-title":"Aging Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1038\/mp.2009.24","article-title":"Population genetic study of the brain-derived neurotrophic factor (BDNF) gene","volume":"15","author":"Petryshen","year":"2010","journal-title":"Mol. Psychiatry"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"156","DOI":"10.3389\/fnmol.2018.00156","article-title":"Critical issues in BDNF Val66met genetic studies of neuropsychiatric disorders","volume":"11","author":"Tsai","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"56","DOI":"10.4306\/pi.2013.10.1.56","article-title":"Association between the BDNF Val66Met Polymorphism and Chronicity of Depression","volume":"10","author":"Lee","year":"2013","journal-title":"Psychiatry Investig."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"827658","DOI":"10.3389\/fpsyt.2022.888774","article-title":"Evaluation of the Relationship Between BDNF Val66Met Gene Polymorphism and Attention Deficit Hyperactivity Disorder: A Meta-Analysis","volume":"13","author":"Mei","year":"2022","journal-title":"Front. Psychiatry"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1097\/YPG.0000000000000237","article-title":"Brain-derived neurotrophic factor and schizophrenia","volume":"29","author":"Punzi","year":"2019","journal-title":"Psychiatr. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"685041","DOI":"10.3389\/fpsyt.2021.685041","article-title":"The Brain-Derived Neurotrophic Factor Val66Met Polymorphism Is Associated With Female Obsessive-Compulsive Disorder: An Updated Meta-Analysis of 2765 Obsessive-Compulsive Disorder Cases and 5558 Controls","volume":"12","author":"Shang","year":"2022","journal-title":"Front. Psychiatry"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s10194-017-0725-2","article-title":"The association between brain-derived neurotrophic factor gene polymorphism and migraine: A meta-analysis","volume":"18","author":"Cai","year":"2017","journal-title":"J. Headache Pain"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s12017-018-8519-5","article-title":"BDNF rs6265 (Val66Met) Polymorphism as a Risk Factor for Blepharospasm","volume":"21","author":"Siokas","year":"2019","journal-title":"NeuroMol. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1177\/0300060517748843","article-title":"Serum concentration and clinical significance of brain-derived neurotrophic factor in patients with Parkinson\u2019s disease or essential tremor","volume":"46","author":"Huang","year":"2018","journal-title":"J. Int. Med. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1007\/s00415-009-5357-2","article-title":"Serum levels of brain-derived neurotrophic factor correlate with motor impairment in Parkinson\u2019s disease","volume":"257","author":"Scalzo","year":"2010","journal-title":"J. Neurol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Razgado-Hernandez, L.F., Espadas-Alvarez, A.J., Reyna-Velazquez, P., Sierra-Sanchez, A., Anaya-Martinez, V., Jimenez-Estrada, I., Bannon, M.J., Martinez-Fong, D., and Aceves-Ruiz, J. (2015). The transfection of BDNF to dopamine neurons potentiates the effect of dopamine D3 receptor agonist recovering the striatal innervation, dendritic spines and motor behavior in an aged rat model of Parkinson\u2019s disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0117391"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1523\/JNEUROSCI.3920-03.2004","article-title":"Early Striatal Dendrite Deficits followed by Neuron Loss with Advanced Age in the Absence of Anterograde Cortical Brain-Derived Neurotrophic Factor","volume":"24","author":"Baquet","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1006\/exnr.2000.7483","article-title":"Reduced BDNF mRNA expression in the Parkinson\u2019s disease substantia nigra","volume":"166","author":"Howells","year":"2000","journal-title":"Exp. Neurol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/0896-6273(91)90273-3","article-title":"BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer\u2019s disease","volume":"7","author":"Phillips","year":"1991","journal-title":"Neuron"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1001\/archneur.57.6.846","article-title":"Region-Specific Neurotrophin Imbalances in Alzheimer Disease","volume":"57","author":"Hock","year":"2000","journal-title":"Arch. Neurol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1097\/00001756-199611250-00024","article-title":"Regional specificity of alterations in NGF, BDNF and NT-3 levels in Alzheimer\u2019s disease","volume":"7","author":"Wakabayashi","year":"1996","journal-title":"Neuroreport"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1111\/j.1471-4159.2005.03135.x","article-title":"Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer\u2019s disease","volume":"93","author":"Peng","year":"2005","journal-title":"J. Neurochem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0006-8993(00)02237-X","article-title":"Brain-derived neurotrophic factor in Huntington disease","volume":"866","author":"Ferrer","year":"2000","journal-title":"Brain Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S1353-8020(02)00008-1","article-title":"Elevated glial brain-derived neurotrophic factor in Parkinson\u2019s diseased nigra","volume":"8","author":"Knott","year":"2002","journal-title":"Park. Relat. Disord."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/mp.2013.105","article-title":"Serum BDNF concentrations as peripheral manifestations of depression: Evidence from a systematic review and meta-analyses on 179 associations (N = 9484)","volume":"19","author":"Molendijk","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1007\/s12035-018-1283-6","article-title":"Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation","volume":"56","author":"Doorduin","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/S0006-3223(03)00181-1","article-title":"Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants","volume":"54","author":"Shimizu","year":"2003","journal-title":"Biol. Psychiatry"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e619","DOI":"10.1038\/tp.2015.114","article-title":"BDNF promoter methylation and genetic variation in late-life depression","volume":"5","author":"Januar","year":"2015","journal-title":"Transl. Psychiatry"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1017\/S1461145708009000","article-title":"Brain-derived neurotrophic factor and tyrosine kinase B receptor signalling in post-mortem brain of teenage suicide victims","volume":"11","author":"Pandey","year":"2008","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1001\/archpsyc.60.8.804","article-title":"Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects","volume":"60","author":"Dwivedi","year":"2003","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1038\/sj.mp.4001308","article-title":"Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia","volume":"8","author":"Weickert","year":"2003","journal-title":"Mol. Psychiatry"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/sj.mp.4001678","article-title":"Reductions in neurotrophin receptor mRNAs in the prefrontal cortex of patients with schizophrenia","volume":"10","author":"Weickert","year":"2005","journal-title":"Mol. Psychiatry"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.nbd.2015.03.011","article-title":"Evaluation of TrkB and BDNF transcripts in prefrontal cortex, hippocampus, and striatum from subjects with schizophrenia, bipolar disorder, and major depressive disorder","volume":"77","author":"Reinhart","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1523\/JNEUROSCI.4035-04.2005","article-title":"Relationship of brain-derived neurotrophic factor and its receptor TrkB to altered inhibitory prefrontal circuitry in schizophrenia","volume":"25","author":"Hashimoto","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/j.pnpbp.2009.08.011","article-title":"Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics","volume":"33","author":"Xiu","year":"2009","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Sortwell, C.E., Hacker, M.L., Fischer, D.L., Konrad, P.E., Davis, T.L., Neimat, J.S., Wang, L., Song, Y., Mattingly, Z.R., and Cole-Strauss, A. BDNF rs6265 Genotype Influences Outcomes of Pharmacotherapy and Subthalamic Nucleus Deep Brain Stimulation in Early-Stage Parkinson\u2019s Disease. Neuromodulation, 2021. in press.","DOI":"10.1111\/ner.13504"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.parkreldis.2018.05.003","article-title":"Bdnf variant is associated with milder motor symptom severity in early-stage Parkinson\u2019s disease","volume":"53","author":"Fischer","year":"2018","journal-title":"Park. Relat. Disord."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"568","DOI":"10.2174\/1389202914666131210212521","article-title":"Pharmacogenetics of Parkinson\u2019s Disease\u2014Through Mechanisms of Drug Actions","volume":"14","author":"Drozdzik","year":"2014","journal-title":"Curr. Genomics"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1212\/01.wnl.0000187075.81589.fd","article-title":"BDNF genetic variants are associated with onset age of familial Parkinson disease: GenePD Study","volume":"65","author":"Karamohamed","year":"2005","journal-title":"Neurology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/ajmg.b.30986","article-title":"Sexually dimorphic effect of the Val66Met oolymorphism of BDNF on susceptibility to Alzheimer\u2019s disease: New data and meta-analysis","volume":"153","author":"Fukumoto","year":"2010","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1007\/s11357-011-9275-8","article-title":"Brain-derived neurotrophic factor (BDNF) gene: A gender-specific role in cognitive function during normal cognitive aging of the MEMO-Study?","volume":"34","author":"Laing","year":"2012","journal-title":"Age"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"867","DOI":"10.3233\/JAD-2009-1191","article-title":"BDNF genetic variations increase the risk of Alzheimer\u2019s disease-related depression","volume":"18","author":"Borroni","year":"2009","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1212\/01.wnl.0000175977.57661.b1","article-title":"Association between BDNF Val66Met polymorphism and age at onset in Huntington disease","volume":"65","author":"Alberch","year":"2005","journal-title":"Neurology"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3389\/fpsyt.2020.00038","article-title":"Association Between BDNF Gene Variant Rs6265 and the Severity of Depression in Antidepressant Treatment-Free Depressed Patients","volume":"11","author":"Losenkov","year":"2020","journal-title":"Front. Psychiatry"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1002\/ajmg.b.32062","article-title":"The brain-derived neurotrophic-factor (BDNF) val66met polymorphism is associated with geriatric depression: A meta-analysis","volume":"159B","author":"Pei","year":"2012","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Hosang, G.M., Shiles, C., Tansey, K.E., McGuffin, P., and Uher, R. (2014). Interaction between stress and the BDNF Val66Met polymorphism in depression: A systematic review and meta-analysis. BMC Med., 12.","DOI":"10.1186\/1741-7015-12-7"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s10571-015-0229-z","article-title":"Brain-Derived Neurotrophic Factor Gene Val66Met Polymorphism and Risk of Schizophrenia: A Meta-analysis of Case\u2013Control Studies","volume":"36","author":"Kheirollahi","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.biopsych.2006.08.025","article-title":"Brain-Derived Neurotrophic Factor Val66Met and Psychiatric Disorders: Meta-Analysis of Case-Control Studies Confirm Association to Substance-Related Disorders, Eating Disorders, and Schizophrenia","volume":"61","author":"Mercader","year":"2007","journal-title":"Biol. Psychiatry"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1176\/appi.neuropsych.11100234","article-title":"BDNF val66met polymorphism is associated with age at onset and intensity of symptoms of paranoid schizophrenia in a Polish population","volume":"25","author":"Suchanek","year":"2013","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.brainres.2011.08.037","article-title":"Lack of effect of brain derived neurotrophic factor (BDNF) Val66Met polymorphism on early onset schizophrenia in Chinese Han population","volume":"1417","author":"Yi","year":"2011","journal-title":"Brain Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1002\/ajmg.b.30619","article-title":"BDNF Val66Met variant and age of onset in schizophrenia","volume":"147","author":"Chao","year":"2008","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/nrneurol.2009.54","article-title":"Brain-derived neurotrophic factor in neurodegenerative diseases","volume":"5","author":"Zuccato","year":"2009","journal-title":"Nat. Rev. Neurol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","article-title":"Parkinson\u2019s disease","volume":"397","author":"Bloem","year":"2021","journal-title":"Lancet"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/S0006-8993(00)03217-0","article-title":"Differential expression of GDNF, BDNF, and NT-3 in the aging nigrostriatal system following a neurotoxic lesion","volume":"891","author":"Yurek","year":"2001","journal-title":"Brain Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/350230a0","article-title":"BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra","volume":"350","author":"Hyman","year":"1991","journal-title":"Nature"},{"key":"ref_122","first-page":"1021","article-title":"BDNF in the Aged Brain: Translational Implications for Parkinson\u2019s Disease","volume":"2","author":"Mercado","year":"2017","journal-title":"Austin Neurol. Neurosci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0301-0082(00)00014-9","article-title":"Brain-derived neurotrophic factor in the control human brain, and in Alzheimer\u2019s disease and Parkinson\u2019s disease","volume":"63","author":"Murer","year":"2001","journal-title":"Prog. Neurobiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"901082","DOI":"10.1155\/2013\/901082","article-title":"Serum brain-derived neurotrophic factor levels in different neurological diseases","volume":"2013","author":"Ventriglia","year":"2013","journal-title":"Biomed Res. Int."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Jin, W. (2020). Regulation of bdnf-trkb signaling and potential therapeutic strategies for parkinson\u2019s disease. J. Clin. Med., 9.","DOI":"10.3390\/jcm9010257"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s10735-013-9562-z","article-title":"Expression of full-length and truncated trkB in human striatum and substantia nigra neurons: Implications for Parkinson\u2019s disease","volume":"45","author":"Fenner","year":"2014","journal-title":"J. Mol. Histol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1042\/CS20160044","article-title":"Neurotrophin signalling: Novel insights into mechanisms and pathophysiology","volume":"131","author":"Mitre","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.expneurol.2004.11.030","article-title":"Inhibiting BDNF expression by antisense oligonucleotide infusion causes loss of nigral dopaminergic neurons","volume":"192","author":"Porritt","year":"2005","journal-title":"Exp. Neurol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Fedosova, A., Titova, N., Kokaeva, Z., Shipilova, N., Katunina, E., and Klimov, E. (2021). Genetic markers as risk factors for the development of impulsive-compulsive behaviors in patients with parkinson\u2019s disease receiving dopaminergic therapy. J. Pers. Med., 11.","DOI":"10.3390\/jpm11121321"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Gorzkowska, A., Cholewa, J., Cholewa, J., Wilk, A., and Klimkowicz-Mrowiec, A. (2021). Risk factors for apathy in Polish patients with parkinson\u2019s disease. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph181910196"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1007\/s13311-020-00965-9","article-title":"BDNF rs6265 Variant Alters Outcomes with Levodopa in Early-Stage Parkinson\u2019s Disease","volume":"17","author":"Fischer","year":"2020","journal-title":"Neurotherapeutics"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1136\/jnnp.2008.154294","article-title":"BDNF val66met influences time to onset of levodopa induced dyskinesia in Parkinson\u2019s disease","volume":"80","author":"Foltynie","year":"2009","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.neulet.2013.12.051","article-title":"BDNF G196A (Val66Met) polymorphism associated with cognitive impairment in Parkinson\u2019s disease","volume":"561","author":"Kurzawski","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1159\/000352033","article-title":"No association between brain-derived neurotrophic factor g196a polymorphism and clinical features of parkinson\u2019s disease","volume":"70","author":"Svetel","year":"2013","journal-title":"Eur. Neurol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1002\/mds.22759","article-title":"Levodopa response in early Parkinson\u2019s disease","volume":"24","author":"Hauser","year":"2009","journal-title":"Mov. Disord."},{"key":"ref_136","unstructured":"(2022, June 06). Parkinson\u2019s Disease 2014: Advancing Research, Improving Lives, U.S. Dep. Heal. Hum. Serv. (n.d.), Available online: https:\/\/www.ninds.nih.gov\/parkinsons-disease-2014-advancing-research-improving-lives."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s11481-015-9637-6","article-title":"Tau-Directed Immunotherapy: A Promising Strategy for Treating Alzheimer\u2019s Disease and Other Tauopathies","volume":"11","author":"Schroeder","year":"2016","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.bbr.2016.05.030","article-title":"Molecular and cellular pathophysiology of preclinical Alzheimer\u2019s disease","volume":"311","author":"Mufson","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","article-title":"The neuropathological diagnosis of Alzheimer\u2019s disease","volume":"14","author":"Deture","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.5114\/aoms.2015.56342","article-title":"Brain-derived neurotrophic factor and its clinical Implications","volume":"11","author":"Bathina","year":"2015","journal-title":"Arch. Med. Sci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"104540","DOI":"10.1016\/j.nbd.2019.104540","article-title":"Brain-derived neurotrophic factor (BDNF) and TrkB hippocampal gene expression are putative predictors of neuritic plaque and neurofibrillary tangle pathology","volume":"132","author":"Ginsberg","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/S0306-4522(98)00219-X","article-title":"An immunohistochemical study of the distribution of brain-derived neurotrophic factor in the adult human brain, with particular reference to Alzheimer\u2019s disease","volume":"88","author":"Murer","year":"1999","journal-title":"Neuroscience"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1097\/00005072-199907000-00007","article-title":"BDNF and full-length and truncated TrkB expression in Alzheimer disease. Implications in therapeutic strategies","volume":"58","author":"Ferrer","year":"1999","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.jpsychires.2006.01.014","article-title":"BDNF serum and CSF concentrations in Alzheimer\u2019s disease, normal pressure hydrocephalus and healthy controls","volume":"41","author":"Laske","year":"2007","journal-title":"J. Psychiatr. Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.neurobiolaging.2018.04.004","article-title":"Sexual dimorphism in predisposition to Alzheimer\u2019s disease","volume":"70","author":"Fisher","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"192-e11","DOI":"10.1016\/j.neurobiolaging.2016.12.023","article-title":"Female-specific effect of the BDNF gene on Alzheimer\u2019s disease","volume":"53","author":"Li","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1002\/ana.10842","article-title":"Brain-Derived Neurotrophic Factor Genetic Variants Are Not Susceptibility Factors to Alzheimer\u2019s Disease in Italy","volume":"55","author":"Bagnoli","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3233\/JAD-2006-9104","article-title":"The brain-derived neurotrophic factor Val66Met polymorphism and rate of decline in Alzheimer\u2019s disease","volume":"9","author":"Chuu","year":"2006","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1159\/000106473","article-title":"Lack of association between the BDNF gene Val66Met polymorphism and Alzheimer disease in a Chinese Han population","volume":"55","author":"He","year":"2007","journal-title":"Neuropsychobiology"},{"key":"ref_150","first-page":"12","article-title":"No association between the brain-derived neurotrophic factor 196G>A or 270C>T polymorphisms and Alzheimer\u2019s or Parkinson\u2019s disease","volume":"44","author":"Saarela","year":"2006","journal-title":"Folia Neuropathol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"a024240","DOI":"10.1101\/cshperspect.a024240","article-title":"Huntington\u2019s disease: Mechanisms of pathogenesis and therapeutic strategies","volume":"7","author":"Licitra","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.pneurobio.2007.01.003","article-title":"Role of brain-derived neurotrophic factor in Huntington\u2019s disease","volume":"81","author":"Zuccato","year":"2007","journal-title":"Prog. Neurobiol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/j.1750-3639.2007.00111.x","article-title":"Systematic assessment of BDNF and its receptor levels in human cortices affected by Huntington\u2019s disease","volume":"18","author":"Zuccato","year":"2008","journal-title":"Brain Pathol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1126\/science.1059581","article-title":"Loss of huntingtin-mediated BDNF gene transcription in Huntington\u2019s disease","volume":"293","author":"Zuccato","year":"2001","journal-title":"Science"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.neuron.2014.05.032","article-title":"Impaired TrkB receptor signaling underlies corticostriatal dysfunction in Huntington\u2019s disease","volume":"83","author":"Plotkin","year":"2014","journal-title":"Neuron"},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Mai, M., Akkad, A.D., Wieczorek, S., Saft, C., Andrich, J., Kraus, P.H., Epplen, J.T., and Arning, L. (2006). No association between polymorphisms in the BDNF gene and age at onset in Huntington disease. BMC Med. Genet., 7.","DOI":"10.1186\/1471-2350-7-79"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.nbd.2006.07.002","article-title":"No evidence of association between BDNF gene variants and age-at-onset of Huntington\u2019s disease","volume":"24","author":"Marasco","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.nbd.2006.07.008","article-title":"Brain-derived neurotrophic factor does not influence age at neurologic onset of Huntington\u2019s disease","volume":"24","author":"Kishikawa","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00439-006-0221-2","article-title":"Genetic analysis of candidate genes modifying the age-at-onset in Huntington\u2019s disease","volume":"120","author":"Metzger","year":"2006","journal-title":"Hum. Genet."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1007\/s00213-018-4950-4","article-title":"Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression","volume":"235","author":"Levy","year":"2018","journal-title":"Psychopharmacology"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.jpsychires.2012.05.003","article-title":"Depression, the Val66Met polymorphism, age, and gender influence the serum BDNF level","volume":"46","author":"Elfving","year":"2012","journal-title":"J. Psychiatr. Res."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1503\/jpn.100048","article-title":"Decreased BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders","volume":"36","author":"Ray","year":"2011","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1038\/npp.2014.262","article-title":"Chronic amitriptyline treatment attenuates nigrostriatal degeneration and significantly alters trophic support in a rat model of parkinsonism","volume":"40","author":"Paumier","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1093\/ijnp\/pyy008","article-title":"Association of BDNF Val66MET polymorphism and brain BDNF levels with major depression and suicide","volume":"21","author":"Youssef","year":"2018","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3389\/fgene.2015.00230","article-title":"DNA methylation and single nucleotide variants in the brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) genes are associated with anxiety\/depression in older women","volume":"6","author":"Chagnon","year":"2015","journal-title":"Front. Genet."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"112832","DOI":"10.1016\/j.bbr.2020.112832","article-title":"Association of circulating BDNF levels with BDNF rs6265 polymorphism in schizophrenia","volume":"394","author":"Kumar","year":"2020","journal-title":"Behav. Brain Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"113022","DOI":"10.1016\/j.biopha.2022.113022","article-title":"Targeting \u03b16GABAA receptors as a novel therapy for schizophrenia: A proof-of-concept preclinical study using various animal models","volume":"150","author":"Lee","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1177\/02698811221078751","article-title":"The cortical silent period in schizophrenia: A systematic review and meta-analysis focusing on disease stage and antipsychotic medication","volume":"36","author":"Miyazawa","year":"2022","journal-title":"J. Psychopharmacol."},{"key":"ref_169","first-page":"47","article-title":"The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: Old fashioned, but still in vogue","volume":"5","author":"Brisch","year":"2014","journal-title":"Front. Psychiatry"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3389\/fpsyt.2013.00045","article-title":"BDNF and schizophrenia: From neurodevelopment to neuronal plasticity, learning, and memory","volume":"4","author":"Nieto","year":"2013","journal-title":"Front. Psychiatry"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1038\/mp.2010.88","article-title":"Brain-derived neurotrophic factor levels in schizophrenia: A systematic review with meta-analysis","volume":"16","author":"Green","year":"2011","journal-title":"Mol. Psychiatry"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0165-1781(02)00127-0","article-title":"Decreased levels of brain-derived neurotrophic factor in serum of chronic schizophrenic patients","volume":"110","author":"Toyooka","year":"2002","journal-title":"Psychiatry Res."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.biopsych.2014.08.012","article-title":"Brain-derived neurotrophic factor epigenetic modifications associated with schizophrenia-like phenotype induced by prenatal stress in mice","volume":"77","author":"Dong","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/mp.2012.110","article-title":"Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia","volume":"18","author":"Fillman","year":"2013","journal-title":"Mol. Psychiatry"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/sj.mp.4000718","article-title":"Abnormal expression of brain-derived neurotrophic factor and its receptor in the corticolimbic system of schizophrenic patients","volume":"5","author":"Takahashi","year":"2000","journal-title":"Mol. Psychiatry"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1037\/neu0000383","article-title":"Suicide attempt, clinical correlates, and BDNF Val66Met polymorphism in chronic patients with schizophrenia","volume":"32","author":"Xia","year":"2018","journal-title":"Neuropsychology"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.pharep.2017.08.002","article-title":"Val66Met functional polymorphism and serum protein level of brain-derived neurotrophic factor (BDNF) in acute episode of schizophrenia and depression","volume":"70","author":"Skibinska","year":"2018","journal-title":"Pharmacol. Rep."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.humimm.2011.05.018","article-title":"Functional variants of the genes involved in neurodevelopment and susceptibility to schizophrenia in an Armenian population","volume":"72","author":"Zakharyan","year":"2011","journal-title":"Hum. Immunol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neulet.2006.02.054","article-title":"Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism in schizophrenia is associated with age at onset and symptoms","volume":"401","author":"Numata","year":"2006","journal-title":"Neurosci. Lett."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/0169-328X(96)00062-9","article-title":"The mesolimbic dopaminergic pathway is more resistant than the nigrostriatal dopaminergic pathway to MPTP and MPP+ toxicity: Role of BDNF gene expression","volume":"41","author":"Hung","year":"1996","journal-title":"Mol. Brain Res."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.nbd.2008.05.012","article-title":"Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats","volume":"31","author":"Arancibia","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1080\/14712598.2016.1183641","article-title":"Engineered BDNF producing cells as a potential treatment for neurologic disease","volume":"16","author":"Deng","year":"2016","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1046\/j.1471-4159.1994.63031021.x","article-title":"Efficacy of Brain-Derived Neurotrophic Factor and Neurotrophin-3 on Neurochemical and Behavioral Deficits Associated with Partial Nigrostriatal Dopamine Lesions","volume":"63","author":"Altar","year":"1994","journal-title":"J. Neurochem."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1212\/WNL.52.7.1427","article-title":"A controlled trial of recombinant methionyl human BDNF in ALS","volume":"52","author":"Bradley","year":"1999","journal-title":"Neurology"},{"key":"ref_185","first-page":"201","article-title":"A phase I\/II trial of recombinant methionyl human brain derived neurotrophic factor administered by intrathecal infusion to patients with amyotrophic lateral sclerosis","volume":"1","author":"Ochs","year":"2000","journal-title":"Amyotroph. Lateral Scler."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1080\/14660820310006689","article-title":"A prospective, randomized, placebo-controlled evaluation of corticoneuronal response to intrathecal BDNF therapy in ALS using magnetic resonance spectroscopy: Feasibility and results","volume":"4","author":"Kalra","year":"2003","journal-title":"Amyotroph. Lateral Scler. Other Mot. Neuron Disord."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"983","DOI":"10.4103\/1673-5374.233438","article-title":"The brain-derived neurotrophic factor in neuronal plasticity and neuroregeneration: New pharmacological concepts for old and new drugs","volume":"13","author":"Habtemariam","year":"2018","journal-title":"Neural Regen. Res."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13034-016-0097-4","article-title":"Association of peripheral BDNF level with cognition, attention and behavior in preschool children","volume":"10","author":"Yeom","year":"2016","journal-title":"Child Adolesc. Psychiatry Ment. Health"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nrd3366","article-title":"Potential therapeutic uses of BDNF in neurological and psychiatric disorders","volume":"10","author":"Nagahara","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"637","DOI":"10.2147\/NDT.S227598","article-title":"A study of antidepressant effect and mechanism on intranasal delivery of BDNF-HA2TAT\/AAV to rats with post-stroke depression","volume":"16","author":"Chen","year":"2020","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.ymthe.2004.02.016","article-title":"AAV-mediated gene delivery of BDNF or GDNF is neuroprotective in a model of Huntington disease","volume":"9","author":"Kells","year":"2004","journal-title":"Mol. Ther."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"593572","DOI":"10.3389\/fnagi.2020.593572","article-title":"The Future of GDNF in Parkinson\u2019s Disease","volume":"12","author":"Manfredsson","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/S1474-4422(10)70254-4","article-title":"Gene delivery of AAV2-neurturin for Parkinson\u2019s disease: A double-blind, randomised, controlled trial","volume":"9","author":"Marks","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1080\/14737175.2020.1763794","article-title":"Gene therapy for Parkinson\u2019s disease: Contemporary practice and emerging concepts","volume":"20","author":"Merola","year":"2020","journal-title":"Expert Rev. Neurother."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"7810","DOI":"10.1523\/JNEUROSCI.15-12-07810.1995","article-title":"Intrastriatal implantation of fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevents degeneration of dopaminergic neurons in a rat model of Parkinson\u2019s disease","volume":"15","author":"Levivier","year":"1995","journal-title":"J. Neurosci."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3390\/brainsci4010202","article-title":"Use of genetically altered stem cells for the treatment of Huntington\u2019s disease","volume":"4","author":"Crane","year":"2014","journal-title":"Brain Sci."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nm1239","article-title":"A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease","volume":"11","author":"Tuszynski","year":"2005","journal-title":"Nat. Med."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1182\/blood-2002-07-2314","article-title":"Side effects of retroviral gene transfer into hematopoietic stem cells","volume":"101","author":"Baum","year":"2003","journal-title":"Blood"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ymthe.2003.10.013","article-title":"Chance or necessity? Insertional mutagenesis in gene therapy and its consequences","volume":"9","author":"Baum","year":"2004","journal-title":"Mol. Ther."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"5820","DOI":"10.1038\/s41467-020-19505-2","article-title":"The once and future gene therapy","volume":"11","author":"Bulaklak","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.neuint.2015.07.021","article-title":"7,8-Dihydroxyflavone as a pro-neurotrophic treatment for neurodevelopmental disorders","volume":"89","author":"Du","year":"2015","journal-title":"Neurochem. Int."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13024-016-0119-y","article-title":"Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: Emerging therapeutic modality for Alzheimer\u2019s disease","volume":"11","author":"Kazim","year":"2016","journal-title":"Mol. Neurodegener."},{"key":"ref_203","doi-asserted-by":"crossref","unstructured":"Cardenas-Aguayo, M.d.C., Kazim, S.F., Grundke-Iqbal, I., and Iqbal, K. (2013). Neurogenic and Neurotrophic Effects of BDNF Peptides in Mouse Hippocampal Primary Neuronal Cell Cultures. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053596"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"14336","DOI":"10.1038\/s41598-021-87435-0","article-title":"Dimeric mimetic of BDNF loop 4 promotes survival of serum-deprived cell through TrkB-dependent apoptosis suppression","volume":"11","author":"Zainullina","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nrd4024","article-title":"Small-molecule modulation of neurotrophin receptors: A strategy for the treatment of neurological disease","volume":"12","author":"Longo","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.bbr.2013.09.029","article-title":"7,8-Dihydroxyflavone improves memory consolidation processes in rats and mice","volume":"257","author":"Bollen","year":"2013","journal-title":"Behav. Brain Res."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/npp.2011.191","article-title":"7,8-dihydroxyflavone, a small-molecule TrkB agonist, reverses memory deficits and BACE1 elevation in a mouse model of alzheimer\u2019s disease","volume":"37","author":"Devi","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1073\/pnas.0913572107","article-title":"A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone","volume":"107","author":"Jang","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"16825","DOI":"10.1038\/s41598-017-17201-8","article-title":"Aerobic exercise and a BDNF-mimetic therapy rescue learning and memory in a mouse model of Down syndrome","volume":"7","author":"Parrini","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1002\/med.21721","article-title":"Low-molecular mimetics of nerve growth factor and brain-derived neurotrophic factor: Design and pharmacological properties","volume":"41","author":"Gudasheva","year":"2021","journal-title":"Med. Res. Rev."},{"key":"ref_211","doi-asserted-by":"crossref","unstructured":"Gudasheva, T.A., Tallerova, A.V., Mezhlumyan, A.G., Antipova, T.A., Logvinov, I.O., Firsova, Y.N., Povarnina, P.Y., and Seredenin, S.B. (2021). Low-molecular weight bdnf mimetic, dimeric dipeptide GSB-106, reverses depressive symptoms in mouse chronic social defeat stress. Biomolecules, 11.","DOI":"10.3390\/biom11020252"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"18171","DOI":"10.1073\/pnas.0405831102","article-title":"Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson\u2019s disease","volume":"101","author":"Maswood","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1046\/j.1471-4159.2001.00071.x","article-title":"Brain-derived neurotrophic factor mediates an excitoprotective effect of dietary restriction in mice","volume":"76","author":"Duan","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1152\/physrev.00004.2002","article-title":"Modification of brain aging and neurodegenerative disorders by genes, diet, and behavior","volume":"82","author":"Mattson","year":"2002","journal-title":"Physiol. Rev."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"553-e1","DOI":"10.1016\/j.neurobiolaging.2010.03.019","article-title":"BDNF increases with behavioral enrichment and an antioxidant diet in the aged dog","volume":"33","author":"Fahnestock","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.neuroscience.2012.09.063","article-title":"Physical training exerts neuroprotective effects in the regulation of neurochemical factors in an animal model of Parkinson\u2019s disease","volume":"227","author":"Tuon","year":"2012","journal-title":"Neuroscience"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.bbi.2010.09.006","article-title":"Running exercise protects the substantia nigra dopaminergic neurons against inflammation-induced degeneration via the activation of BDNF signaling pathway","volume":"25","author":"Wu","year":"2011","journal-title":"Brain. Behav. Immun."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s00702-010-0474-8","article-title":"Running wheel activity restores MPTP-induced functional deficits","volume":"118","author":"Fredriksson","year":"2011","journal-title":"J. Neural Transm."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.brainres.2009.10.075","article-title":"Exercise exerts neuroprotective effects on Parkinson\u2019s disease model of rats","volume":"1310","author":"Tajiri","year":"2010","journal-title":"Brain Res."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1111\/j.1460-9568.2011.07626.x","article-title":"Neuroprotective effects and mechanisms of exercise in a chronic mouse model of Parkinson\u2019s disease with moderate neurodegeneration","volume":"33","author":"Lau","year":"2011","journal-title":"Eur. J. Neurosci."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.nbd.2013.11.017","article-title":"Treadmill exercise reverses dendritic spine loss in direct and indirect striatal medium spiny neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson\u2019s disease","volume":"63","author":"Toy","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"5291","DOI":"10.1523\/JNEUROSCI.1069-07.2007","article-title":"Effects of treadmill exercise on dopaminergic transmission in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury","volume":"27","author":"Petzinger","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"R713","DOI":"10.1016\/j.apmr.2007.05.015","article-title":"Six Weeks of Intensive Treadmill Training Improves Gait and Quality of Life in Patients With Parkinson\u2019s Disease: A Pilot Study","volume":"88","author":"Herman","year":"2007","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1249\/01.mss.0000487954.94993.25","article-title":"Parkinson\u2019s Disease Patients Show Long-term Gait Improvements After Active Assistive Forced Exercise Training","volume":"48","author":"Stuckenschneider","year":"2016","journal-title":"Med. Sci. Sport. Exerc."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/j.apmr.2008.01.013","article-title":"(Janice); Yip, J.; Cen, S.; Gordon, J.; Jakowec, M.; Petzinger, G. The Effect of Exercise Training in Improving Motor Performance and Corticomotor Excitability in People with Early Parkinson\u2019s Disease","volume":"89","author":"Fisher","year":"2008","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_226","doi-asserted-by":"crossref","unstructured":"Gerecke, K.M., Jiao, Y., Pagala, V., and Smeyne, R.J. (2012). Exercise does not protect against MPTP-induced neurotoxicity in BDNF happloinsufficent mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043250"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.neuroscience.2013.01.060","article-title":"BDNF receptor blockade hinders the beneficial effects of exercise in a rat model of Parkinson\u2019s disease","volume":"237","author":"Real","year":"2013","journal-title":"Neuroscience"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jpsychires.2014.10.003","article-title":"A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor","volume":"60","author":"Szuhany","year":"2015","journal-title":"J. Psychiatr. Res."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1249\/MSS.0000000000002242","article-title":"Exercise Intensity and Recovery on Circulating Brain-derived Neurotrophic Factor","volume":"52","author":"Reycraft","year":"2020","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.gene.2019.02.067","article-title":"Differential BDNF methylation in combat exposed veterans and the association with exercise","volume":"698","author":"Voisey","year":"2019","journal-title":"Gene"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/jnc.13993","article-title":"Growth factors and hormones pro-peptides: The unexpected adventures of the BDNF prodomain","volume":"141","author":"Zanin","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/bs.vh.2016.11.006","article-title":"BDNF Propeptide: A Novel Modulator of Synaptic Plasticity","volume":"104","author":"Kojima","year":"2017","journal-title":"Vitam. Horm."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/nn.2244","article-title":"Neuronal release of proBDNF","volume":"12","author":"Yang","year":"2009","journal-title":"Nat. Neurosci."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1097\/WNR.0000000000000828","article-title":"Brain-derived neurotrophic factor propeptide inhibits proliferation and induces apoptosis in C6 glioma cells","volume":"28","author":"Yang","year":"2017","journal-title":"Neuroreport"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"e2264","DOI":"10.1038\/cddis.2016.166","article-title":"BDNF pro-peptide regulates dendritic spines via caspase-3","volume":"7","author":"Guo","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1177\/1545968319846131","article-title":"The Val66Met BDNF Polymorphism and Peripheral Nerve Injury: Enhanced Regeneration in Mouse Met-Carriers Is Not Further Improved With Activity-Dependent Treatment","volume":"33","author":"McGregor","year":"2019","journal-title":"Neurorehabil. Neural Repair"},{"key":"ref_237","doi-asserted-by":"crossref","unstructured":"Barbey, A.K., Colom, R., Paul, E., Forbes, C., Krueger, F., Goldman, D., and Grafman, J. (2014). Preservation of general intelligence following traumatic brain injury: Contributions of the Met66 brain-derived neurotrophic factor. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088733"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1523\/JNEUROSCI.1399-10.2011","article-title":"The role of the met66 brain-derived neurotrophic factor allele in the recovery of executive functioning after combat-related traumatic brain injury","volume":"31","author":"Krueger","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.3233\/JAD-180585","article-title":"The Influence of the Val66Met Polymorphism of Brain-Derived Neurotrophic Factor on Neurological Function after Traumatic Brain Injury","volume":"65","author":"Finan","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1093\/hmg\/ddm189","article-title":"Preservation of gray matter volume in multiple sclerosis patients with the Met allele of the rs6265 (Val66Met) SNP of brain-derived neurotrophic factor","volume":"16","author":"Zivadinov","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s00441-019-03034-6","article-title":"BDNF pro-peptide: Physiological mechanisms and implications for depression","volume":"377","author":"Kojima","year":"2019","journal-title":"Cell Tissue Res."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.jpsychires.2019.03.024","article-title":"Cerebrospinal fluid BDNF pro-peptide levels in major depressive disorder and schizophrenia","volume":"113","author":"Mizui","year":"2019","journal-title":"J. Psychiatr. Res."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"3929","DOI":"10.1093\/hmg\/ddv130","article-title":"The pro-domains of neurotrophins, including BDNF, are linked to Alzheimer\u2019s disease through a toxic synergy with A\u03b2","volume":"24","author":"Lim","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s00406-016-0693-6","article-title":"Regional differences in the expression of brain-derived neurotrophic factor (BDNF) pro-peptide, proBDNF and preproBDNF in the brain confer stress resilience","volume":"266","author":"Yang","year":"2016","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"e1128","DOI":"10.1038\/tp.2017.95","article-title":"Altered expression of BDNF, BDNF pro-peptide and their precursor proBDNF in brain and liver tissues from psychiatric disorders: Rethinking the brain-liver axis","volume":"7","author":"Yang","year":"2017","journal-title":"Transl. Psychiatry"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1017\/S1121189X00000816","article-title":"The potential role of the parietal lobe in schizophrenia","volume":"19","author":"Bellani","year":"2010","journal-title":"Epidemiol. Psichiatr. Soc."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"581686","DOI":"10.1155\/2011\/581686","article-title":"Parietal Lobes in Schizophrenia: Do They Matter?","volume":"2011","author":"Yildiz","year":"2011","journal-title":"Schizophr. Res. Treatment"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"128","DOI":"10.3389\/fnbeh.2021.699592","article-title":"Functional Contribution of the Medial Prefrontal Circuitry in Major Depressive Disorder and Stress-Induced Depressive-Like Behaviors","volume":"15","author":"Bittar","year":"2021","journal-title":"Front. Behav. Neurosci."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00429-008-0189-x","article-title":"Brain structural and functional abnormalities in mood disorders: Implications for neurocircuitry models of depression","volume":"213","author":"Drevets","year":"2008","journal-title":"Brain Struct. Funct."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1038\/nm.2886","article-title":"Decreased expression of synapse-related genes and loss of synapses in major depressive disorder","volume":"18","author":"Kang","year":"2012","journal-title":"Nat. Med."},{"key":"ref_251","first-page":"282","article-title":"The role of the nucleus accumbens in psychiatric disorders","volume":"25","author":"Mavridis","year":"2015","journal-title":"Psychiatrike"},{"key":"ref_252","first-page":"9","article-title":"Brain-Derived Neurotrophic Factor: Three Ligands, Many Actions","volume":"126","author":"Hempstead","year":"2015","journal-title":"Trans. Am. Clin. Climatol. Assoc."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"a001818","DOI":"10.1101\/cshperspect.a001818","article-title":"Rho and Ras GTPases in axon growth, guidance, and branching","volume":"2","author":"Hall","year":"2010","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.phrs.2015.12.008","article-title":"Activation of a synapse weakening pathway by human Val66 but not Met66 pro-brain-derived neurotrophic factor (proBDNF)","volume":"104","author":"Kailainathan","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1001\/archgenpsychiatry.2010.194","article-title":"The brain-derived neurotrophic factor Val66Met polymorphism and prediction of neural risk for alzheimer disease","volume":"68","author":"Voineskos","year":"2011","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1523\/JNEUROSCI.4140-13.2014","article-title":"An adaptive role for BDNF Val66Met polymorphism in motor recovery in chronic stroke","volume":"34","author":"Qin","year":"2014","journal-title":"J. Neurosci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/14\/8011\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:54:47Z","timestamp":1760140487000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/14\/8011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,20]]},"references-count":256,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijms23148011"],"URL":"https:\/\/doi.org\/10.3390\/ijms23148011","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,20]]}}}