{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:04:51Z","timestamp":1792789491094,"version":"4.5.0"},"reference-count":106,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grant-in-Aid for Scientific Research","award":["JSPS KA-KENHI 24K09645"],"award-info":[{"award-number":["JSPS KA-KENHI 24K09645"]}]},{"name":"Grant-in-Aid for Scientific Research","award":["JSPS KAKENHI 23K07772"],"award-info":[{"award-number":["JSPS KAKENHI 23K07772"]}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology of Japan","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Japanese Society of Inherited Metabolic Disease\/Sanofi LSD Research"},{"DOI":"10.13039\/100012045","name":"Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012045","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brain-derived growth factor, BDNF, has critical roles in a wide variety of neuronal aspects, including cell survival, differentiation, and synaptic function after their maturation. TrkB, a high-affinity receptor for BDNF, is a major contributor in these neuronal aspects, and its functions are exerted via stimulating intracellular signaling pathways including the mitogen-activated protein kinase (MAPK) pathways. As a family of MAPKs, the functions of ERK1\/2, p38MAPK, and JNKs have been extensively studied using in vivo and in vitro neuronal systems. ERK 1\/2, a major serine-threonine kinase and belonging to the MAPK family, also works as a downstream molecule after activation of the BDNF\/TrkB system. Interestingly, growing evidence has demonstrated that ERK1\/2 signaling exerts a positive or negative influence on neurons in both healthy and pathological conditions in the central nervous system (CNS). Indeed, activation of ERK 1\/2 stimulated by the BDNF\/TrkB system is involved in the regulation of synaptic plasticity. On the other hand, overactivation of ERK1\/2 signaling under pathological conditions is closely related to neurodegeneration. Furthermore, cell stress activates p38MAPKs and JNK signaling, contributing to the progression of neurodegeneration. In this review, we show how MAPK pathway signaling affects neuronal fate, including cell survival or cell death, in the CNS. Moreover, we discuss the involvement of overactivation of MAPK signaling in the neurodegeneration observed in Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), and Huntington\u2019s disease (HD).<\/jats:p>","DOI":"10.3390\/ijms27020984","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T13:02:07Z","timestamp":1768914127000},"page":"984","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Roles of MAPKs, Including Those Activated by BDNF\/TrkB, and Their Contribution in Neurodegenerative Diseases"],"prefix":"10.3390","volume":"27","author":[{"given":"Tadahiro","family":"Numakawa","sequence":"first","affiliation":[{"name":"Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0908-2543","authenticated-orcid":false,"given":"Ryutaro","family":"Kajihara","sequence":"additional","affiliation":[{"name":"Department of Hematology and Immunology, Faculty of Life Science, Kumamoto University, Kumamoto 862-0976, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"ref_1","first-page":"237","article-title":"BDNF function and intracellular signaling in neurons","volume":"25","author":"Numakawa","year":"2010","journal-title":"Histol. 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