{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:48:39Z","timestamp":1790999319906,"version":"4.1.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2018\/06260-8"],"award-info":[{"award-number":["2018\/06260-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2020\/08840-1"],"award-info":[{"award-number":["2020\/08840-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2016\/20796-2"],"award-info":[{"award-number":["2016\/20796-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2019\/02821-8"],"award-info":[{"award-number":["2019\/02821-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/10863-7"],"award-info":[{"award-number":["2017\/10863-7"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurotox Res"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tau is a neuronal protein that confers stability to microtubules; however, its hyperphosphorylation and accumulation can lead to an impairment of protein degradation pathways, such as autophagy. Autophagy is a lysosomal catabolic process responsible for degrading cytosolic components, being essential for cellular homeostasis and survival. In this context, autophagy modulation has been postulated as a possible therapeutic target for the treatment of neurodegenerative diseases. Studies point to the modulatory and neuroprotective role of the cannabinoid system in neurodegenerative models and here it was investigated the effects of cannabidiol (CBD) on autophagy in a human neuroblastoma strain (SH-SY5Y) that overexpresses the EGFP-Tau WT (Wild Type) protein in an inducible Tet-On system way. The results demonstrated that CBD (100 nM and 10 \u00b5M) decreased the expression of AT8 and total tau proteins, activating autophagy, evidenced by increased expression of light chain 3-II (LC3-II) protein and formation of autophagosomes. Furthermore, the cannabinoid compounds CBD, ACEA (CB1 agonist) and GW-405,833 (CB2 agonist) decreased the fluorescence intensity of EGFP-Tau WT; and when chloroquine, an autophagic blocker, was used, there was a reversal in the fluorescence intensity of EGFP-Tau WT with CBD (1 and 10 \u00b5M) and GW-405,833 (2 \u00b5M), demonstrating the possible participation of autophagy in these groups. Thus, it was possible to conclude that CBD induced autophagy in EGFP-Tau WT cells which increased tau degradation, showing its possible neuroprotective role. Hence, this study may contribute to a better understanding of how cannabinoids can modulate autophagy and present a potential therapeutic target in a neurodegeneration model.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s12640-025-00729-3","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T22:52:11Z","timestamp":1738623131000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Cannabidiol-Induced Autophagy Ameliorates Tau Protein Clearance"],"prefix":"10.1007","volume":"43","author":[{"given":"Talita A. M.","family":"Vrechi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel C.","family":"Guarache","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela Brito","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika da Cruz","family":"Guedes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo G.","family":"Erustes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anderson H. F. F.","family":"Le\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa C.","family":"Ab\u00edlio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio W.","family":"Zuardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime Eduardo C.","family":"Hallak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Alexandre","family":"Crippa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Bincoletto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo P.","family":"Ureshino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soraya S.","family":"Smaili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo J. S.","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"729_CR2","doi-asserted-by":"publisher","first-page":"439","DOI":"10.3233\/JAD-2012-111862","volume":"30","author":"E Aso","year":"2012","unstructured":"Aso E, Palomer E, Juv\u00e9s S et al (2012) CB1 agonist ACEA protects neurons and reduces the cognitive impairment of A\u03b2PP\/PS1 mice. J Alzheimer\u2019s Dis 30:439\u2013459. https:\/\/doi.org\/10.3233\/JAD-2012-111862","journal-title":"J Alzheimer\u2019s Dis"},{"key":"729_CR3","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1111\/jnc.14098","volume":"142","author":"BS Basavarajappa","year":"2017","unstructured":"Basavarajappa BS, Shivakumar M, Joshi V, Subbanna S (2017) Endocannabinoid system in neurodegenerative disorders. J Neurochem 142:624\u2013648. https:\/\/doi.org\/10.1111\/jnc.14098","journal-title":"J Neurochem"},{"key":"729_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-021-22501-9","volume":"12","author":"B Caballero","year":"2021","unstructured":"Caballero B, Bourdenx M, Luengo E et al (2021) Acetylated tau inhibits chaperone-mediated autophagy and promotes tau pathology propagation in mice. Nat Commun 12:1\u201318. https:\/\/doi.org\/10.1038\/s41467-021-22501-9","journal-title":"Nat Commun"},{"key":"729_CR5","doi-asserted-by":"publisher","first-page":"525","DOI":"10.3233\/JAD-130050","volume":"35","author":"MJ Casarejos","year":"2013","unstructured":"Casarejos MJ, Perucho J, Gomez A et al (2013) Natural cannabinoids improve dopamine neurotransmission and tau and amyloid pathology in a mouse model of tauopathy. J Alzheimer\u2019s Dis 35:525\u2013539. https:\/\/doi.org\/10.3233\/JAD-130050","journal-title":"J Alzheimer\u2019s Dis"},{"key":"729_CR6","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/j.disamonth.2010.06.001","volume":"56","author":"RJ Castellani","year":"2010","unstructured":"Castellani RJ, Rolston RK, Smith MA (2010) Alzheimer disease. Dis Mon 56:484\u2013546. https:\/\/doi.org\/10.1016\/j.disamonth.2010.06.001","journal-title":"Dis Mon"},{"key":"729_CR7","doi-asserted-by":"publisher","first-page":"609","DOI":"10.4161\/auto.19048","volume":"8","author":"EE Congdon","year":"2012","unstructured":"Congdon EE, Wu JW, Myeku N et al (2012) Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitro and in vivo. Autophagy 8:609\u2013622. https:\/\/doi.org\/10.4161\/auto.19048","journal-title":"Autophagy"},{"key":"729_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-017-13311-5","volume":"7","author":"MI Cosacak","year":"2017","unstructured":"Cosacak MI, Bhattarai P, Bocova L et al (2017) Human TAUP301L overexpression results in TAU hyperphosphorylation without neurofibrillary tangles in adult zebrafish brain. Sci Rep 7:1\u201314. https:\/\/doi.org\/10.1038\/s41598-017-13311-5","journal-title":"Sci Rep"},{"key":"729_CR9","doi-asserted-by":"publisher","first-page":"148079","DOI":"10.1016\/J.BRAINRES.2022.148079","volume":"1795","author":"AJ Costa","year":"2022","unstructured":"Costa AJ, Oliveira RB, Wachilewski P et al (2022) Membrane estrogen receptor ER\u03b1 activation improves tau clearance via autophagy induction in a tauopathy cell model. Brain Res 1795:148079. https:\/\/doi.org\/10.1016\/J.BRAINRES.2022.148079","journal-title":"Brain Res"},{"key":"729_CR10","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.biopsych.2019.05.008","volume":"87","author":"A Di Meco","year":"2020","unstructured":"Di Meco A, Curtis ME, Lauretti E, Pratic\u00f2 D (2020) Autophagy dysfunction in Alzheimer\u2019s Disease: mechanistic insights and New Therapeutic opportunities. Biol Psychiatry 87:797\u2013807. https:\/\/doi.org\/10.1016\/j.biopsych.2019.05.008","journal-title":"Biol Psychiatry"},{"key":"729_CR11","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1172\/JCI29715","volume":"117","author":"CA Dickey","year":"2007","unstructured":"Dickey CA, Kamal A, Lundgren K et al (2007) The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins. J Clin Invest 117:648\u2013658. https:\/\/doi.org\/10.1172\/JCI29715","journal-title":"J Clin Invest"},{"key":"729_CR12","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s00109-005-0025-1","volume":"84","author":"G Esposito","year":"2006","unstructured":"Esposito G, De Filippis D, Carnuccio R et al (2006) The marijuana component cannabidiol inhibits \u03b2-amyloid-induced tau protein hyperphosphorylation through Wnt\/\u03b2-catenin pathway rescue in PC12 cells. J Mol Med 84:253\u2013258. https:\/\/doi.org\/10.1007\/s00109-005-0025-1","journal-title":"J Mol Med"},{"key":"729_CR13","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1038\/sj.bjp.0707337","volume":"151","author":"G Esposito","year":"2007","unstructured":"Esposito G, Scuderi C, Savani C et al (2007) Cannabidiol in vivo blunts b-amyloid induced neuroinflammation by suppressing IL-1b and iNOS expression. Br J Pharmacol 151:1272\u20131279. https:\/\/doi.org\/10.1038\/sj.bjp.0707337","journal-title":"Br J Pharmacol"},{"key":"729_CR14","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/82_2010_64","volume":"2","author":"ME Feldman","year":"2010","unstructured":"Feldman ME, Shokat KM (2010) New inhibitors of the PI3K-Akt-mTOR pathway: insights into mTOR Signaling from a New Generation of Tor kinase domain inhibitors (TORKinibs). Phosphoinositide 3-kinase Heal Dis 2:241\u2013262. https:\/\/doi.org\/10.1007\/82_2010_64","journal-title":"Phosphoinositide 3-kinase Heal Dis"},{"key":"729_CR15","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.coph.2021.07.011","volume":"60","author":"BP Festa","year":"2021","unstructured":"Festa BP, Barbosa AD, Rob M, Rubinsztein DC (2021) The pleiotropic roles of autophagy in Alzheimer\u2019s disease: from pathophysiology to therapy. Curr Opin Pharmacol 60:149\u2013157. https:\/\/doi.org\/10.1016\/j.coph.2021.07.011","journal-title":"Curr Opin Pharmacol"},{"key":"729_CR16","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.1007\/s00018-015-1839-9","volume":"72","author":"SN Fontaine","year":"2015","unstructured":"Fontaine SN, Sabbagh JJ, Baker J et al (2015) Cellular factors modulating the mechanism of tau protein aggregation. Cell Mol Life Sci 72:1863\u20131879. https:\/\/doi.org\/10.1007\/s00018-015-1839-9","journal-title":"Cell Mol Life Sci"},{"key":"729_CR17","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/ncb1528","volume":"9","author":"TA Fulga","year":"2007","unstructured":"Fulga TA, Elson-Schwab I, Khurana V et al (2007) Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo. Nat Cell Biol 9:139\u2013148. https:\/\/doi.org\/10.1038\/ncb1528","journal-title":"Nat Cell Biol"},{"key":"729_CR18","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1007\/s12031-011-9593-4","volume":"45","author":"M Goedert","year":"2011","unstructured":"Goedert M, Spillantini MG (2011) Pathogenesis of the tauopathies. J Mol Neurosci 45:425\u2013431. https:\/\/doi.org\/10.1007\/s12031-011-9593-4","journal-title":"J Mol Neurosci"},{"key":"729_CR19","doi-asserted-by":"publisher","first-page":"104553","DOI":"10.1016\/j.fitote.2020.104553","volume":"143","author":"A Gugliandolo","year":"2020","unstructured":"Gugliandolo A, Pollastro F, Bramanti P, Mazzon E (2020) Cannabidiol exerts protective effects in an in vitro model of Parkinson\u2019s disease activating AKT\/mTOR pathway. Fitoterapia 143:104553. https:\/\/doi.org\/10.1016\/j.fitote.2020.104553","journal-title":"Fitoterapia"},{"key":"729_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms22147475","volume":"22","author":"T Hamano","year":"2021","unstructured":"Hamano T, Enomoto S, Shirafuji N et al (2021) Autophagy and tau protein. Int J Mol Sci 22:1\u201320. https:\/\/doi.org\/10.3390\/ijms22147475","journal-title":"Int J Mol Sci"},{"key":"729_CR21","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1038\/nature04724","volume":"441","author":"T Hara","year":"2006","unstructured":"Hara T, Nakamura K, Matsui M et al (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441:885\u2013889. https:\/\/doi.org\/10.1038\/nature04724","journal-title":"Nature"},{"key":"729_CR22","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12839","author":"C Hiebel","year":"2014","unstructured":"Hiebel C, Kromm T, Stark M, Behl C (2014) Cannabinoid receptor 1 modulates the autophagic flux independent of mTOR- and BECLIN1-complex. J Neurochem. https:\/\/doi.org\/10.1111\/jnc.12839","journal-title":"J Neurochem"},{"key":"729_CR23","doi-asserted-by":"publisher","first-page":"502","DOI":"10.4161\/auto.5.4.8096","volume":"5","author":"SY Hung","year":"2009","unstructured":"Hung SY, Huang WP, Liou HC, Fu WM (2009) Autophagy protects neuron from A\u03b2-induced cytotoxicity. Autophagy 5:502\u2013510. https:\/\/doi.org\/10.4161\/auto.5.4.8096","journal-title":"Autophagy"},{"key":"729_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1750-1326-7-48","volume":"7","author":"K Inoue","year":"2012","unstructured":"Inoue K, Rispoli J, Kaphzan H et al (2012) Macroautophagy deficiency mediates age-dependent neurodegeneration through a phospho-tau pathway. Mol Neurodegener 7:1\u201313. https:\/\/doi.org\/10.1186\/1750-1326-7-48","journal-title":"Mol Neurodegener"},{"key":"729_CR25","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/s10571-013-9984-x","volume":"34","author":"E Janefjord","year":"2014","unstructured":"Janefjord E, M\u00e5\u00e5g JLV, Harvey BS, Smid SD (2014) Cannabinoid effects on \u03b2 amyloid fibril and aggregate formation, neuronal and microglial-activated neurotoxicity in vitro. Cell Mol Neurobiol 34:31\u201342. https:\/\/doi.org\/10.1007\/s10571-013-9984-x","journal-title":"Cell Mol Neurobiol"},{"key":"729_CR26","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/nature04723","volume":"441","author":"M Komatsu","year":"2006","unstructured":"Komatsu M, Waguri S, Chiba T et al (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441:880\u2013884. https:\/\/doi.org\/10.1038\/nature04723","journal-title":"Nature"},{"key":"729_CR27","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1016\/j.neurobiolaging.2011.11.009","volume":"33","author":"U Kr\u00fcger","year":"2012","unstructured":"Kr\u00fcger U, Wang Y, Kumar S, Mandelkow EM (2012) Autophagic degradation of tau in primary neurons and its enhancement by trehalose. Neurobiol Aging 33:2291\u20132305. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2011.11.009","journal-title":"Neurobiol Aging"},{"key":"729_CR28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms18010026","volume":"18","author":"R Libro","year":"2017","unstructured":"Libro R, Diomede F, Scionti D et al (2017) Cannabidiol modulates the expression of alzheimer\u2019s disease-related genes in mesenchymal stem cells. Int J Mol Sci 18:1\u201319. https:\/\/doi.org\/10.3390\/ijms18010026","journal-title":"Int J Mol Sci"},{"key":"729_CR29","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1016\/j.neurobiolaging.2008.02.012","volume":"30","author":"YH Liu","year":"2009","unstructured":"Liu YH, Wei W, Yin J et al (2009) Proteasome inhibition increases tau accumulation independent of phosphorylation. Neurobiol Aging 30:1949\u20131961. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2008.02.012","journal-title":"Neurobiol Aging"},{"key":"729_CR30","doi-asserted-by":"publisher","first-page":"10912","DOI":"10.18632\/aging.103305","volume":"12","author":"Z Long","year":"2020","unstructured":"Long Z, Chen J, Zhao Y et al (2020) Dynamic changes of autophagic flux induced by Abeta in the brain of postmortem Alzheimer\u2019s disease patients, animal models and cell models. Aging 12:10912\u201310930. https:\/\/doi.org\/10.18632\/aging.103305","journal-title":"Aging"},{"key":"729_CR31","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.071290","author":"AM Martin-Moreno","year":"2011","unstructured":"Martin-Moreno AM, Reigada D, Ramirez BG et al (2011) Cannabidiol and other Cannabinoids reduce Microglial Activation in Vitro and in vivo: relevance to Alzheimer\u2019s Disease. Mol Pharmacol. https:\/\/doi.org\/10.1124\/mol.111.071290","journal-title":"Mol Pharmacol"},{"key":"729_CR32","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1741-7007-10-78","volume":"10","author":"M Nassif","year":"2012","unstructured":"Nassif M, Hetz C (2012) Autophagy impairment: a crossroad between neurodegeneration and tauopathies. BMC Biol 10:4\u20137. https:\/\/doi.org\/10.1186\/1741-7007-10-78","journal-title":"BMC Biol"},{"key":"729_CR33","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s40478-016-0292-9","volume":"4","author":"A Piras","year":"2016","unstructured":"Piras A, Collin L, Gr\u00fcninger F et al (2016) Autophagic and lysosomal defects in human tauopathies: analysis of post-mortem brain from patients with familial Alzheimer disease, corticobasal degeneration and progressive supranuclear palsy. Acta Neuropathol Commun 4:22. https:\/\/doi.org\/10.1186\/s40478-016-0292-9","journal-title":"Acta Neuropathol Commun"},{"key":"729_CR34","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1111\/j.1471-4159.2010.06838.x","volume":"114","author":"VN Pivtoraiko","year":"2010","unstructured":"Pivtoraiko VN, Harrington AJ, Mader BJ et al (2010) Low-dose bafilomycin attenuates neuronal cell death associated with autophagy-lysosome pathway dysfunction. J Neurochem 114:1193\u20131204. https:\/\/doi.org\/10.1111\/j.1471-4159.2010.06838.x","journal-title":"J Neurochem"},{"key":"729_CR35","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.mad.2013.08.001","volume":"134","author":"A Piyanova","year":"2013","unstructured":"Piyanova A, Albayram O, Rossi CA et al (2013) Loss of CB1 receptors leads to decreased cathepsin D levels and accelerated lipofuscin accumulation in the hippocampus. Mech Ageing Dev 134:391\u2013399. https:\/\/doi.org\/10.1016\/j.mad.2013.08.001","journal-title":"Mech Ageing Dev"},{"key":"729_CR36","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1007\/s11011-017-0137-7","volume":"33","author":"M Salama","year":"2018","unstructured":"Salama M, Elhussiny M, Magdy A et al (2018) Dual mTORC1\/mTORC2 blocker as a possible therapy for tauopathy in cellular model. Metab Brain Dis 33:583\u2013587. https:\/\/doi.org\/10.1007\/s11011-017-0137-7","journal-title":"Metab Brain Dis"},{"key":"729_CR37","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1111\/cns.12349","volume":"20","author":"BZ Shao","year":"2014","unstructured":"Shao BZ, Wei W, Ke P et al (2014) Activating cannabinoid receptor 2 alleviates pathogenesis of experimental autoimmune encephalomyelitis via activation of autophagy and inhibiting NLRP3 inflammasome. CNS Neurosci Ther 20:1021\u20131028. https:\/\/doi.org\/10.1111\/cns.12349","journal-title":"CNS Neurosci Ther"},{"key":"729_CR38","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1038\/s41418-018-0217-1","volume":"26","author":"JM Silva","year":"2019","unstructured":"Silva JM, Rodrigues S, Sampaio-Marques B et al (2019) Dysregulation of autophagy and stress granule-related proteins in stress-driven tau pathology. Cell Death Differ 26:1411\u20131427. https:\/\/doi.org\/10.1038\/s41418-018-0217-1","journal-title":"Cell Death Differ"},{"key":"729_CR39","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s004010050487","volume":"92","author":"MG Spillantini","year":"1996","unstructured":"Spillantini MG, Goedert M, Crowther RA (1996) Comparison of the neurofibrillary pathology in Alzheimer\u2019s disease and familial presenile dementia with tangles. Acta Neuropathol 92:42\u201348","journal-title":"Acta Neuropathol"},{"key":"729_CR40","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.bbadis.2004.06.017","volume":"1739","author":"WH Stoothoff","year":"2005","unstructured":"Stoothoff WH, Johnson GVW (2005) Tau phosphorylation: physiological and pathological consequences. Biochim Biophys Acta - Mol Basis Dis 1739:280\u2013297. https:\/\/doi.org\/10.1016\/j.bbadis.2004.06.017","journal-title":"Biochim Biophys Acta - Mol Basis Dis"},{"key":"729_CR1","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1002\/cpt.117","volume":"97","author":"AIA Van Der Ahmed","year":"2015","unstructured":"Van Der Ahmed AIA, Olde Rikkert MGM (2015) Cannabinoids in late-onset Alzheimer\u2019s Disease. Clin Pharmacol Ther 97:597\u2013606. https:\/\/doi.org\/10.1002\/cpt.117","journal-title":"Clin Pharmacol Ther"},{"key":"729_CR41","doi-asserted-by":"publisher","first-page":"5434","DOI":"10.1038\/s41598-021-84879-2","volume":"11","author":"TAM Vrechi","year":"2021","unstructured":"Vrechi TAM, Le\u00e3o AHFF, Morais IBM et al (2021) Cannabidiol induces autophagy via ERK1\/2 activation in neural cells. Sci Rep 11:5434. https:\/\/doi.org\/10.1038\/s41598-021-84879-2","journal-title":"Sci Rep"},{"key":"729_CR42","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.pneurobio.2008.03.002","volume":"85","author":"JZ Wang","year":"2008","unstructured":"Wang JZ, Liu F (2008) Microtubule-associated protein tau in development, degeneration and protection of neurons. Prog Neurobiol 85:148\u2013175. https:\/\/doi.org\/10.1016\/j.pneurobio.2008.03.002","journal-title":"Prog Neurobiol"},{"key":"729_CR43","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1038\/ncb0910-814","volume":"12","author":"Z Yang","year":"2010","unstructured":"Yang Z, Klionsky DJ (2010) Eaten alive: a history of macroautophagy. Nat Cell Biol 12:814\u2013822. https:\/\/doi.org\/10.1038\/ncb0910-814","journal-title":"Nat Cell Biol"},{"key":"729_CR44","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1515\/revneuro-2017-0013","volume":"28","author":"Y Zhang","year":"2017","unstructured":"Zhang Y, Chen X, Zhao Y et al (2017) The role of ubiquitin proteasomal system and autophagy-lysosome pathway in Alzheimer\u2019s disease. Rev Neurosci 28:861\u2013868. https:\/\/doi.org\/10.1515\/revneuro-2017-0013","journal-title":"Rev Neurosci"}],"container-title":["Neurotoxicity Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12640-025-00729-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12640-025-00729-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12640-025-00729-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T00:55:17Z","timestamp":1743296117000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12640-025-00729-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["729"],"URL":"https:\/\/doi.org\/10.1007\/s12640-025-00729-3","relation":{},"ISSN":["1029-8428","1476-3524"],"issn-type":[{"value":"1029-8428","type":"print"},{"value":"1476-3524","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"6 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 December 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 January 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"J.A.C. reported receiving grants from the National Institute of Translational Science and Technology in Medicine and personal fees from the National Council for Scientific and Technological Development (CNPq 1\u00a0A) during the conduct of the study, being a co-owner of a patent for fluorinated cannabidiol compounds (licensed to Phytecs) and having a patent pending for a cannabinoid-containing oral pharmaceutical composition outside the submitted work. J.A.C. is a consultant and\/or has received speaker fees and\/or sits on the advisory board and\/or receives research funding from Janssen-Cilag, EaseLabs Pharm, DSM-Pharm, Torrent, GreenCare, PurMed Global, BioSynthesis Pharma Group (BSPG), and Prati-Donaduzzi. J.A.C. reported receiving grants from FAPESP.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"8"}}