{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:58:47Z","timestamp":1793066327927,"version":"4.5.0"},"reference-count":73,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:00:00Z","timestamp":1773532800000},"content-version":"vor","delay-in-days":73,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e0 degli Studi del Piemonte Orientale Amedeo Avogrado"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Parkinson's disease (PD) is a neurodegenerative disorder characterised by dopamine deficiency and the accumulation of \u03b1-synuclein (\u03b1-syn), which aggregates into pathological inclusions known as Lewy bodies and Lewy neurites, distributed across multiple brain regions, with a particular prevalence in dopaminergic neurons. Alongside hallmark motor symptoms, PD is often accompanied by non-motor manifestations that severely affect patients\u2019 quality of life. Levodopa remains the most effective therapy; however, it is associated with a wide range of side effects and shows little to no efficacy against non-motor symptoms. This study investigates the neuroprotective effects of a combination of four bioactive compounds\u2014green tea, saffron, docosahexaenoic acid (DHA) and \u03b1-lipoic acid (ALA)\u2014against the PD-related neurodegeneration. Their ability to cross the blood\u2013brain barrier (BBB) while maintaining its integrity was evaluated using a validated in vitro model. Individual and combined effects of these compounds were assessed on mesencephalic dopaminergic cells exposed to 6-hydroxydopamine (6-OHDA), a widely used in vitro model of PD-like neurotoxicity. The results demonstrated that the combined treatment (Mix) significantly restored cell viability after 6-OHDA exposure and more effectively reduced oxidative and nitrosative stress, as well as lipid peroxidation, compared to single compounds. Furthermore, the Mix markedly decreased the production of pro-inflammatory cytokines (including tumour necrosis factor-alpha (TNF-\u03b1) and interleukins) and downregulated the expression of PTEN-induced kinase 1 (PINK1) and Parkin, two key markers of PD-related neurodegeneration. In conclusion, these results indicate that the Mix has a suggest a synergistic-like impact on various disease-causing pathways in PD, highlighting its promise as a multi-faceted neuroprotective approach.<\/jats:p>","DOI":"10.1007\/s12035-026-05800-4","type":"journal-article","created":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T06:25:38Z","timestamp":1773555938000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neuroprotective Effects of the Combination of Green Tea, Saffron, Docosahexaenoic Acid, and \u03b1-Lipoic Acid in an In Vitro Model of Parkinson's Disease"],"prefix":"10.1007","volume":"63","author":[{"given":"Rebecca","family":"Galla","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Mul\u00e8","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Battaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Curti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Romana","family":"Ranieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Parini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Uberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,15]]},"reference":[{"key":"5800_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.13","volume":"3","author":"W Poewe","year":"2017","unstructured":"Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, Schrag AE, Lang AE (2017) Parkinson disease. Nat Rev Dis Primers 3:17013. https:\/\/doi.org\/10.1038\/nrdp.2017.13","journal-title":"Nat Rev Dis Primers"},{"issue":"9","key":"5800_CR2","doi-asserted-by":"publisher","first-page":"404","DOI":"10.5694\/mja17.00993","volume":"208","author":"N Titova","year":"2018","unstructured":"Titova N, Chaudhuri KR (2018) Non-motor Parkinson disease: new concepts and personalised management. Med J Aust 208(9):404\u2013409. https:\/\/doi.org\/10.5694\/mja17.00993","journal-title":"Med J Aust"},{"issue":"2","key":"5800_CR3","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s42485-022-00088-z","volume":"13","author":"S Lehrer","year":"2022","unstructured":"Lehrer S, Rheinstein PH (2022) \u03b1-synuclein enfolds tyrosine hydroxylase and dopamine \u00df-hydroxylase, potentially reducing dopamine and norepinephrine synthesis. J Proteins Proteom 13(2):109\u2013115. https:\/\/doi.org\/10.1007\/s42485-022-00088-z","journal-title":"J Proteins Proteom"},{"issue":"10423","key":"5800_CR4","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/S0140-6736(23)01478-2","volume":"403","author":"HR Morris","year":"2024","unstructured":"Morris HR, Spillantini MG, Sue CM, Williams-Gray CH (2024) The pathogenesis of Parkinson\u2019s disease. Lancet 403(10423):293\u2013304. https:\/\/doi.org\/10.1016\/S0140-6736(23)01478-2","journal-title":"Lancet"},{"issue":"6","key":"5800_CR5","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.1093\/advances\/nmab060","volume":"12","author":"JT Boelens Keun","year":"2021","unstructured":"Boelens Keun JT et al (2021) Dietary approaches to improve efficacy and control side effects of levodopa therapy in Parkinson\u2019s disease: a systematic review. Adv Nutr 12(6):2265\u20132287. https:\/\/doi.org\/10.1093\/advances\/nmab060","journal-title":"Adv Nutr"},{"issue":"1","key":"5800_CR6","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/ene.14108","volume":"27","author":"R Balestrino","year":"2020","unstructured":"Balestrino R, Schapira AHV (2020) Parkinson disease. Eur J Neurol 27(1):27\u201342. https:\/\/doi.org\/10.1111\/ene.14108","journal-title":"Eur J Neurol"},{"issue":"1","key":"5800_CR7","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23010040","volume":"23","author":"F Haddad","year":"2017","unstructured":"Haddad F et al (2017) Dopamine and levodopa prodrugs for the treatment of Parkinson\u2019s disease. Molecules 23(1):40. https:\/\/doi.org\/10.3390\/molecules23010040","journal-title":"Molecules"},{"issue":"3","key":"5800_CR8","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/S1474-4422(17)30004-2","volume":"16","author":"V Voon","year":"2017","unstructured":"Voon V et al (2017) Impulse control disorders and levodopa-induced dyskinesias in Parkinson\u2019s disease: an update. Lancet Neurol 16(3):238\u2013250. https:\/\/doi.org\/10.1016\/S1474-4422(17)30004-2","journal-title":"Lancet Neurol"},{"issue":"4","key":"5800_CR9","doi-asserted-by":"publisher","DOI":"10.4470\/E1000181","volume":"10","author":"A Cartabellotta","year":"2018","unstructured":"Cartabellotta A, Berti F, Patti AL, Quintana S, Eleopra R (2018) Linee guida per la diagnosi e il trattamento della malattia di Parkinson. Evidence 10(4):e1000181. https:\/\/doi.org\/10.4470\/E1000181","journal-title":"Evidence"},{"issue":"10291","key":"5800_CR10","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","volume":"397","author":"BR Bloem","year":"2021","unstructured":"Bloem BR, Okun MS, Klein C (2021) Parkinson\u2019s disease. Lancet 397(10291):2284\u20132303. https:\/\/doi.org\/10.1016\/S0140-6736(21)00218-X","journal-title":"Lancet"},{"issue":"1","key":"5800_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-94255-9","volume":"11","author":"YC Chen","year":"2021","unstructured":"Chen YC, Chen RS, Weng YH, Huang YZ, Chen CC, Hung J, Lin YY (2021) The severity progression of non-motor symptoms in Parkinson\u2019s disease: a 6-year longitudinal study in Taiwanese patients. Sci Rep 11(1):14781. https:\/\/doi.org\/10.1038\/s41598-021-94255-9","journal-title":"Sci Rep"},{"issue":"3","key":"5800_CR12","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/S1474-4422(06)70373-8","volume":"5","author":"KR Chaudhuri","year":"2006","unstructured":"Chaudhuri KR, Healy DG, Schapira AH, National Institute for Clinical Excellence (2006) Non-motor symptoms of Parkinson\u2019s disease: diagnosis and management. Lancet Neurol 5(3):235\u2013245. https:\/\/doi.org\/10.1016\/S1474-4422(06)70373-8","journal-title":"Lancet Neurol"},{"issue":"Suppl 12","key":"5800_CR13","first-page":"S308","volume":"17","author":"KE Lyons","year":"2011","unstructured":"Lyons KE, Pahwa R (2011) The impact and management of nonmotor symptoms of Parkinson\u2019s disease. Am J Manag Care 17(Suppl 12):S308\u2013S314","journal-title":"Am J Manag Care"},{"issue":"1","key":"5800_CR14","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1080\/13510002.2017.1343223","volume":"23","author":"K Parasram","year":"2018","unstructured":"Parasram K (2018) Phytochemical treatments target kynurenine pathway induced oxidative stress. Redox Rep 23(1):25\u201328. https:\/\/doi.org\/10.1080\/13510002.2017.1343223","journal-title":"Redox Rep"},{"issue":"10","key":"5800_CR15","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.4103\/1673-5374.280300","volume":"15","author":"T Farkhondeh","year":"2020","unstructured":"Farkhondeh T, Pourbagher-Shahri AM, Ashrafizadeh M, Folgado SL, Rajabpour-Sanati A, Khazdair MR, Samarghandian S (2020) Green tea catechins inhibit microglial activation which prevents the development of neurological disorders. Neural Regen Res 15(10):1792\u20131798. https:\/\/doi.org\/10.4103\/1673-5374.280300","journal-title":"Neural Regen Res"},{"issue":"13","key":"5800_CR16","doi-asserted-by":"publisher","first-page":"5221","DOI":"10.1523\/JNEUROSCI.4650-14.2015","volume":"35","author":"J Burr\u00e9","year":"2015","unstructured":"Burr\u00e9 J, Sharma M, S\u00fcdhof TC (2015) Definition of a molecular pathway mediating \u03b1-synuclein neurotoxicity. J Neurosci 35(13):5221\u20135232. https:\/\/doi.org\/10.1523\/JNEUROSCI.4650-14.2015","journal-title":"J Neurosci"},{"key":"5800_CR17","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.neuroscience.2014.12.003","volume":"286","author":"M Chen","year":"2015","unstructured":"Chen M et al (2015) Tea polyphenols alleviate motor impairments, dopaminergic neuronal injury, and cerebral \u03b1-synuclein aggregation in MPTP-intoxicated parkinsonian monkeys. Neuroscience 286:383\u2013392. https:\/\/doi.org\/10.1016\/j.neuroscience.2014.12.003","journal-title":"Neuroscience"},{"issue":"2","key":"5800_CR18","doi-asserted-by":"publisher","first-page":"295","DOI":"10.3233\/JAD-2009-1048","volume":"17","author":"L Wang","year":"2009","unstructured":"Wang L, Xu S, Xu X, Chan P (2009) (-)-Epigallocatechin-3-gallate protects SH-SY5Y cells against 6-OHDA-induced cell death through STAT3 activation. J Alzheimers Dis 17(2):295\u2013304. https:\/\/doi.org\/10.3233\/JAD-2009-1048","journal-title":"J Alzheimers Dis"},{"issue":"6","key":"5800_CR19","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1080\/01616412.2021.2024715","volume":"44","author":"G \u00d6zduran","year":"2022","unstructured":"\u00d6zduran G, Becer E, Vatansever HS, Y\u00fccecan S (2022) Neuroprotective effects of catechins in an experimental Parkinson\u2019s disease model and SK-N-AS cells: evaluation of cell viability, anti-inflammatory and anti-apoptotic effects. Neurol Res 44(6):511\u2013523. https:\/\/doi.org\/10.1080\/01616412.2021.2024715","journal-title":"Neurol Res"},{"issue":"2","key":"5800_CR20","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1111\/ggi.12123","volume":"14","author":"H Qi","year":"2014","unstructured":"Qi H, Li S (2014) Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson\u2019s disease. Geriatr Gerontol Int 14(2):430\u2013439. https:\/\/doi.org\/10.1111\/ggi.12123","journal-title":"Geriatr Gerontol Int"},{"issue":"12","key":"5800_CR21","doi-asserted-by":"publisher","first-page":"2364","DOI":"10.1002\/ptr.6181","volume":"32","author":"S Leone","year":"2018","unstructured":"Leone S et al (2018) Phytotherapic use of the Crocus sativus L. (Saffron) and its potential applications: a brief overview. Phytother Res 32(12):2364\u20132375. https:\/\/doi.org\/10.1002\/ptr.6181","journal-title":"Phytother Res"},{"issue":"10","key":"5800_CR22","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.22038\/IJBMS.2023.69824.15197","volume":"26","author":"D Esmaealzadeh","year":"2023","unstructured":"Esmaealzadeh D et al (2023) Pharmacological effects of Safranal: an updated review. Iran J Basic Med Sci 26(10):1131\u20131143. https:\/\/doi.org\/10.22038\/IJBMS.2023.69824.15197","journal-title":"Iran J Basic Med Sci"},{"key":"5800_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2021.145811","volume":"799","author":"E Inoue","year":"2021","unstructured":"Inoue E et al (2021) Saffron ameliorated motor symptoms, short life span and retinal degeneration in Parkinson\u2019s disease fly models. Gene 799:145811. https:\/\/doi.org\/10.1016\/j.gene.2021.145811","journal-title":"Gene"},{"issue":"7","key":"5800_CR24","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27072076","volume":"27","author":"A Siddiqui","year":"2022","unstructured":"Siddiqui A et al (2022) Anti-depressant properties of crocin molecules in saffron. Molecules 27(7):2076. https:\/\/doi.org\/10.3390\/molecules27072076","journal-title":"Molecules"},{"key":"5800_CR25","doi-asserted-by":"publisher","DOI":"10.1177\/11786388231160317","volume":"16","author":"SK Sadat Rafiei","year":"2023","unstructured":"Sadat Rafiei SK et al (2023) Saffron and sleep quality: a systematic review of randomized controlled trials. Nutr Metab Insights 16:11786388231160317. https:\/\/doi.org\/10.1177\/11786388231160317","journal-title":"Nutr Metab Insights"},{"issue":"6","key":"5800_CR26","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1080\/15622975.2021.2013041","volume":"23","author":"J Sarris","year":"2022","unstructured":"Sarris J et al (2022) Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: the World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce. World J Biol Psychiatry 23(6):424\u2013455. https:\/\/doi.org\/10.1080\/15622975.2021.2013041","journal-title":"World J Biol Psychiatry"},{"key":"5800_CR27","doi-asserted-by":"publisher","DOI":"10.1080\/1028415X.2020.1735143","author":"P Li","year":"2020","unstructured":"Li P, Song C (2020) Potential treatment of Parkinson\u2019s disease with omega-3 polyunsaturated fatty acids. Nutr Neurosci. https:\/\/doi.org\/10.1080\/1028415X.2020.1735143","journal-title":"Nutr Neurosci"},{"key":"5800_CR28","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.neuint.2016.10.012","volume":"101","author":"A Ozkan","year":"2016","unstructured":"Ozkan A et al (2016) The protective mechanism of docosahexaenoic acid in mouse model of Parkinson: the role of heme oxygenase. Neurochem Int 101:110\u2013119. https:\/\/doi.org\/10.1016\/j.neuint.2016.10.012","journal-title":"Neurochem Int"},{"issue":"2","key":"5800_CR29","doi-asserted-by":"publisher","first-page":"574","DOI":"10.4103\/NRR.NRR-D-23-00595","volume":"20","author":"O Kerdiles","year":"2025","unstructured":"Kerdiles O et al (2025) Additive neurorestorative effects of exercise and docosahexaenoic acid intake in a mouse model of Parkinson\u2019s disease. Neural Regen Res 20(2):574\u2013586. https:\/\/doi.org\/10.4103\/NRR.NRR-D-23-00595","journal-title":"Neural Regen Res"},{"key":"5800_CR30","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.neuint.2017.03.014.","volume":"108","author":"M Taghizadeh","year":"2017","unstructured":"Taghizadeh M et al (2017) The effects of omega-3 fatty acids and vitamin E co-supplementation on clinical and metabolic status in patients with Parkinson\u2019s disease: a randomized, double-blind, placebo-controlled trial. Neurochem Int 108:183\u2013189. https:\/\/doi.org\/10.1016\/j.neuint.2017.03.014.","journal-title":"Neurochem Int"},{"key":"5800_CR31","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.clineuro.2018.12.006","volume":"176","author":"OR Tamtaji","year":"2019","unstructured":"Tamtaji OR et al (2019) The effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression related to inflammation, insulin and lipid in patients with Parkinson\u2019s disease: a randomized, double-blind, placebo-controlled trial. Clin Neurol Neurosurg 176:116\u2013121. https:\/\/doi.org\/10.1016\/j.clineuro.2018.12.006","journal-title":"Clin Neurol Neurosurg"},{"key":"5800_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2023.137346","volume":"810","author":"Q Zheng","year":"2023","unstructured":"Zheng Q et al (2023) Alpha lipoic acid ameliorates motor deficits by inhibiting ferroptosis in Parkinson\u2019s disease. Neurosci Lett 810:137346. https:\/\/doi.org\/10.1016\/j.neulet.2023.137346","journal-title":"Neurosci Lett"},{"issue":"6","key":"5800_CR33","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12061215","volume":"12","author":"O Kulikova","year":"2023","unstructured":"Kulikova O et al (2023) Neuroprotective efficacy of a nanomicellar complex of carnosine and lipoic acid in a rat model of rotenone-induced Parkinson\u2019s disease. Antioxidants 12(6):1215. https:\/\/doi.org\/10.3390\/antiox12061215","journal-title":"Antioxidants"},{"issue":"12","key":"5800_CR34","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11122420","volume":"11","author":"MDM Viana","year":"2022","unstructured":"Viana MDM et al (2022) Alpha-lipoic acid as an antioxidant strategy for managing neuropathic pain. Antioxidants 11(12):2420. https:\/\/doi.org\/10.3390\/antiox11122420","journal-title":"Antioxidants"},{"issue":"4","key":"5800_CR35","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.joim.2021.03.007","volume":"19","author":"R Abdul-Latif","year":"2021","unstructured":"Abdul-Latif R et al (2021) Natural antioxidants in the management of Parkinson\u2019s disease: review of evidence from cell line and animal models. J Integr Med 19(4):300\u2013310. https:\/\/doi.org\/10.1016\/j.joim.2021.03.007","journal-title":"J Integr Med"},{"key":"5800_CR36","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/7465045","volume":"2024","author":"S Mul\u00e8","year":"2024","unstructured":"Mul\u00e8 S et al (2024) The combined effect of green tea, saffron, resveratrol, and citicoline against neurodegeneration induced by oxidative stress in an in vitro model of cognitive decline. Oxid Med Cell Longev 2024:7465045. https:\/\/doi.org\/10.1155\/2024\/7465045","journal-title":"Oxid Med Cell Longev"},{"key":"5800_CR37","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00249","volume":"13","author":"I Chalatsa","year":"2019","unstructured":"Chalatsa I et al (2019) The Crocus sativus compounds trans-crocin 4 and trans-crocetin modulate the amyloidogenic pathway and tau misprocessing in Alzheimer disease neuronal cell culture models. Front Neurosci 13:249. https:\/\/doi.org\/10.3389\/fnins.2019.00249","journal-title":"Front Neurosci"},{"issue":"10","key":"5800_CR38","doi-asserted-by":"publisher","first-page":"2584","DOI":"10.1002\/ijc.21555","volume":"118","author":"M Lindskog","year":"2006","unstructured":"Lindskog M et al (2006) Neuroblastoma cell death in response to docosahexaenoic acid: sensitization to chemotherapy and arsenic-induced oxidative stress. Int J Cancer 118(10):2584\u20132593. https:\/\/doi.org\/10.1002\/ijc.21555","journal-title":"Int J Cancer"},{"key":"5800_CR39","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/2843121","author":"C Molinari","year":"2019","unstructured":"Molinari C et al (2019) Role of combined lipoic acid and vitamin D3 on astrocytes as a way to prevent brain ageing by induced oxidative stress and iron accumulation. Oxid Med Cell Longev. https:\/\/doi.org\/10.1155\/2019\/2843121","journal-title":"Oxid Med Cell Longev"},{"issue":"14","key":"5800_CR40","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28145527","volume":"28","author":"Q Li","year":"2023","unstructured":"Li Q et al (2023) Artemisinin confers neuroprotection against 6-OHDA-induced neuronal injury in vitro and in vivo through activation of the ERK1\/2 pathway. Molecules 28(14):5527. https:\/\/doi.org\/10.3390\/molecules28145527","journal-title":"Molecules"},{"issue":"9","key":"5800_CR41","doi-asserted-by":"publisher","first-page":"7132","DOI":"10.1007\/s12035-018-0882-6","volume":"55","author":"GP Selvakumar","year":"2018","unstructured":"Selvakumar GP et al (2018) Glia maturation factor dependent inhibition of mitochondrial PGC-1\u03b1 triggers oxidative stress-mediated apoptosis in N27 rat dopaminergic neuronal cells. Mol Neurobiol 55(9):7132\u20137152. https:\/\/doi.org\/10.1007\/s12035-018-0882-6","journal-title":"Mol Neurobiol"},{"issue":"14","key":"5800_CR42","doi-asserted-by":"publisher","first-page":"e3305","DOI":"10.21769\/BioProtoc.3305","volume":"9","author":"MP Jogalekar","year":"2019","unstructured":"Jogalekar MP, Serrano EE (2019) Total RNA isolation from separately established monolayer and hydrogel cultures of human glioblastoma cell line. Bio-protocol 9(14):e3305\u2013e3305. https:\/\/doi.org\/10.21769\/BioProtoc.3305","journal-title":"Bio-protocol"},{"issue":"5","key":"5800_CR43","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci10050285","volume":"10","author":"C Molinari","year":"2020","unstructured":"Molinari C et al (2020) The role of BDNF on aging-modulation markers. Brain Sci 10(5):285. https:\/\/doi.org\/10.3390\/brainsci10050285","journal-title":"Brain Sci"},{"issue":"1","key":"5800_CR44","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-022-03524-1","volume":"22","author":"S Nourmohammadi","year":"2022","unstructured":"Nourmohammadi S et al (2022) Thymol protects against 6-hydroxydopamine-induced neurotoxicity in in vivo and in vitro model of Parkinson\u2019s disease via inhibiting oxidative stress. BMC Complement Med Ther 22(1):40. https:\/\/doi.org\/10.1186\/s12906-022-03524-1","journal-title":"BMC Complement Med Ther"},{"issue":"9","key":"5800_CR45","doi-asserted-by":"publisher","DOI":"10.3390\/nu9091008","volume":"9","author":"F Uberti","year":"2017","unstructured":"Uberti F et al (2017) Iron absorption from three commercially available supplements in gastrointestinal cell lines. Nutrients 9(9):1008. https:\/\/doi.org\/10.3390\/nu9091008","journal-title":"Nutrients"},{"issue":"12","key":"5800_CR46","doi-asserted-by":"publisher","first-page":"1684","DOI":"10.1111\/jphp.12803","volume":"69","author":"C Kulczar","year":"2017","unstructured":"Kulczar C et al (2017) Development of a direct contact astrocyte-human cerebral microvessel endothelial cells blood\u2013brain barrier coculture model. J Pharm Pharmacol 69(12):1684\u20131696. https:\/\/doi.org\/10.1111\/jphp.12803","journal-title":"J Pharm Pharmacol"},{"issue":"12","key":"5800_CR47","doi-asserted-by":"publisher","DOI":"10.3390\/nu17121998","volume":"17","author":"S Mul\u00e8","year":"2025","unstructured":"Mul\u00e8 S et al (2025) Molecular insights into the nociceptive modulation by palmitoylethanolamide and Equisetum arvense extract: an in vitro study across the blood-brain barrier. Nutrients 17(12):1998. https:\/\/doi.org\/10.3390\/nu17121998","journal-title":"Nutrients"},{"issue":"6","key":"5800_CR48","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1093\/infdis\/jix041","volume":"215","author":"S Suwarto","year":"2017","unstructured":"Suwarto S, Sasmono RT, Sinto R, Ibrahim E, Suryamin M (2017) Association of endothelial glycocalyx and tight and adherens junctions with severity of plasma leakage in dengue infection. J Infect Dis 215(6):992\u2013999. https:\/\/doi.org\/10.1093\/infdis\/jix041","journal-title":"J Infect Dis"},{"issue":"1","key":"5800_CR49","doi-asserted-by":"publisher","first-page":"5279","DOI":"10.1080\/21655979.2021.1964158","volume":"12","author":"F Han","year":"2021","unstructured":"Han F, Li S, Zhang R, Yang W, Xu C, Xu X et al (2021) Interleukin-6 promotes ferroptosis in bronchial epithelial cells by inducing reactive oxygen species-dependent lipid peroxidation and disrupting iron homeostasis. Bioengineered 12(1):5279\u20135288. https:\/\/doi.org\/10.1080\/21655979.2021.1964158","journal-title":"Bioengineered"},{"issue":"3","key":"5800_CR50","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1097\/IGC.0000000000000379","volume":"25","author":"D Lattuada","year":"2015","unstructured":"Lattuada D et al (2015) Fimbrial cells exposure to catalytic iron mimics carcinogenic changes. Int J Gynecol Cancer 25(3):389\u2013398. https:\/\/doi.org\/10.1097\/IGC.0000000000000379","journal-title":"Int J Gynecol Cancer"},{"issue":"6","key":"5800_CR51","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.jtcme.2021.05.003","volume":"11","author":"C Molinari","year":"2021","unstructured":"Molinari C et al (2021) Preventing C2C12 muscular cells damage combining magnesium and potassium with vitamin D3 and curcumin. J Tradit Complement Med 11(6):532\u2013544. https:\/\/doi.org\/10.1016\/j.jtcme.2021.05.003","journal-title":"J Tradit Complement Med"},{"key":"5800_CR52","doi-asserted-by":"publisher","unstructured":"Uberti F et al (2021) A combination of \u03b1-lipoic acid (ALA) and palmitoylethanolamide (PEA) blocks endotoxin-induced oxidative stress and cytokine storm: a possible intervention for COVID-19. J Diet Suppl. https:\/\/doi.org\/10.1080\/19390211.2021.1966152","DOI":"10.1080\/19390211.2021.1966152"},{"issue":"6","key":"5800_CR53","doi-asserted-by":"publisher","first-page":"7068","DOI":"10.3892\/ol.2018.9516","volume":"16","author":"K Huang","year":"2018","unstructured":"Huang K et al (2018) Effect of PM2.5 on invasion and proliferation of HeLa cells and the expression of inflammatory cytokines IL-1 and IL-6. Oncol Lett 16(6):7068\u20137073. https:\/\/doi.org\/10.3892\/ol.2018.9516","journal-title":"Oncol Lett"},{"issue":"8","key":"5800_CR54","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0160847","volume":"11","author":"L Gao","year":"2016","unstructured":"Gao L, Zhou W, Symmes B, Freed CR (2016) Re-cloning the N27 dopamine cell line to improve a cell culture model of Parkinson\u2019s disease. PLoS One 11(8):e0160847. https:\/\/doi.org\/10.1371\/journal.pone.0160847","journal-title":"PLoS One"},{"issue":"10","key":"5800_CR55","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1089\/ars.2011.3960","volume":"16","author":"DH Choi","year":"2012","unstructured":"Choi DH, Crist\u00f3v\u00e3o AC, Guhathakurta S, Lee J, Joh TH, Beal MF et al (2012) NADPH oxidase 1-mediated oxidative stress leads to dopamine neuron death in Parkinson\u2019s disease. Antioxid Redox Signal 16(10):1033\u20131045. https:\/\/doi.org\/10.1089\/ars.2011.3960","journal-title":"Antioxid Redox Signal"},{"issue":"1","key":"5800_CR56","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s12906-022-03524-1","volume":"22","author":"S Nourmohammadi","year":"2022","unstructured":"Nourmohammadi S, Yousefi S, Manouchehrabadi M, Farhadi M, Azizi Z, Torkaman-Boutorabi A (2022) Thymol protects against 6-hydroxydopamine-induced neurotoxicity in in vivo and in vitro model of Parkinson\u2019s disease via inhibiting oxidative stress. BMC Complement Med Ther 22(1):40. https:\/\/doi.org\/10.1186\/s12906-022-03524-1","journal-title":"BMC Complement Med Ther"},{"issue":"24","key":"5800_CR57","doi-asserted-by":"publisher","DOI":"10.3390\/cells12242860","volume":"12","author":"LF Cardo","year":"2023","unstructured":"Cardo LF, Monz\u00f3n-Sandoval J, Li Z, Webber C, Li M (2023) Single-cell transcriptomics and in vitro lineage tracing reveals differential susceptibility of human iPSC-derived midbrain dopaminergic neurons in a cellular model of Parkinson\u2019s disease. Cells 12(24):2860. https:\/\/doi.org\/10.3390\/cells12242860","journal-title":"Cells"},{"issue":"21","key":"5800_CR58","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20215402","volume":"20","author":"K Kin","year":"2019","unstructured":"Kin K, Yasuhara T, Kameda M, Date I (2019) Animal models for Parkinson\u2019s disease research: trends in the 2000s. Int J Mol Sci 20(21):5402. https:\/\/doi.org\/10.3390\/ijms20215402","journal-title":"Int J Mol Sci"},{"issue":"6","key":"5800_CR59","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25063264","volume":"25","author":"A Muscolo","year":"2024","unstructured":"Muscolo A, Mariateresa O, Giulio T, Mariateresa R (2024) Oxidative stress: the role of antioxidant phytochemicals in the prevention and treatment of diseases. Int J Mol Sci 25(6):3264. https:\/\/doi.org\/10.3390\/ijms25063264","journal-title":"Int J Mol Sci"},{"key":"5800_CR60","doi-asserted-by":"publisher","DOI":"10.1186\/s12937-016-0179-4","volume":"15","author":"NA Singh","year":"2016","unstructured":"Singh NA, Mandal AK, Khan ZA (2016) Potential neuroprotective properties of epigallocatechin-3-gallate (EGCG). Nutr J 15:60. https:\/\/doi.org\/10.1186\/s12937-016-0179-4","journal-title":"Nutr J"},{"issue":"1","key":"5800_CR61","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1080\/1028415X.2020.1735143","volume":"25","author":"P Li","year":"2022","unstructured":"Li P, Song C (2022) Potential treatment of Parkinson\u2019s disease with omega-3 polyunsaturated fatty acids. Nutr Neurosci 25(1):180\u2013191. https:\/\/doi.org\/10.1080\/1028415X.2020.1735143","journal-title":"Nutr Neurosci"},{"key":"5800_CR62","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2023.137346","volume":"810","author":"Q Zheng","year":"2023","unstructured":"Zheng Q, Ma P, Yang P, Zhai S, He M, Zhang X et al (2023) Alpha lipoic acid ameliorates motor deficits by inhibiting ferroptosis in Parkinson\u2019s disease. Neurosci Lett 810:137346. https:\/\/doi.org\/10.1016\/j.neulet.2023.137346","journal-title":"Neurosci Lett"},{"issue":"12","key":"5800_CR63","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11122420","volume":"11","author":"MDM Viana","year":"2022","unstructured":"Viana MDM, Lauria PSS, Lima AA, Opretzka LCF, Marcelino HR, Villarreal CF (2022) Alpha-lipoic acid as an antioxidant strategy for managing neuropathic pain. Antioxidants 11(12):2420. https:\/\/doi.org\/10.3390\/antiox11122420","journal-title":"Antioxidants"},{"issue":"5","key":"5800_CR64","doi-asserted-by":"publisher","DOI":"10.31083\/j.jin2205132","volume":"22","author":"C Cattaneo","year":"2023","unstructured":"Cattaneo C, Jost WH (2023) Pain in Parkinson\u2019s disease: pathophysiology, classification and treatment. J Integr Neurosci 22(5):132. https:\/\/doi.org\/10.31083\/j.jin2205132","journal-title":"J Integr Neurosci"},{"issue":"5","key":"5800_CR65","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1177\/0300060518756540","volume":"46","author":"E Agathos","year":"2018","unstructured":"Agathos E, Tentolouris A, Eleftheriadou I, Katsaouni P, Nemtzas I, Petrou A et al (2018) Effect of \u03b1-lipoic acid on symptoms and quality of life in patients with painful diabetic neuropathy. J Int Med Res 46(5):1779\u20131790. https:\/\/doi.org\/10.1177\/0300060518756540","journal-title":"J Int Med Res"},{"issue":"9","key":"5800_CR66","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.2174\/1871530320666200506081407","volume":"20","author":"MR El-Nahas","year":"2020","unstructured":"El-Nahas MR, Elkannishy G, Abdelhafez H, Elkhamisy ET, El-Sehrawy AA (2020) Oral alpha lipoic acid treatment for symptomatic diabetic peripheral neuropathy: a randomized double-blinded placebo-controlled study. Endocr Metab Immune Disord Drug Targets 20(9):1531\u20131534. https:\/\/doi.org\/10.2174\/1871530320666200506081407","journal-title":"Endocr Metab Immune Disord Drug Targets"},{"issue":"18","key":"5800_CR67","doi-asserted-by":"publisher","first-page":"2721","DOI":"10.1517\/14656566.2014.972935","volume":"15","author":"N Papanas","year":"2014","unstructured":"Papanas N, Ziegler D (2014) Efficacy of \u03b1-lipoic acid in diabetic neuropathy. Expert Opin Pharmacother 15(18):2721\u20132731. https:\/\/doi.org\/10.1517\/14656566.2014.972935","journal-title":"Expert Opin Pharmacother"},{"key":"5800_CR68","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.brainresbull.2022.09.017","volume":"190","author":"S Zhang","year":"2022","unstructured":"Zhang S, Gan L, Cao F, Wang H, Gong P, Ma C et al (2022) The barrier and interface mechanisms of the brain barrier, and brain drug delivery. Brain Res Bull 190:69\u201383. https:\/\/doi.org\/10.1016\/j.brainresbull.2022.09.017","journal-title":"Brain Res Bull"},{"issue":"15","key":"5800_CR69","doi-asserted-by":"publisher","DOI":"10.3390\/cells13151265","volume":"13","author":"GM Mazzotta","year":"2024","unstructured":"Mazzotta GM, Conte C (2024) Alpha-synuclein toxicity and non-motor Parkinson\u2019s. Cells 13(15):1265. https:\/\/doi.org\/10.3390\/cells13151265","journal-title":"Cells"},{"issue":"18","key":"5800_CR70","doi-asserted-by":"publisher","DOI":"10.3390\/cells11182908","volume":"11","author":"B Ara\u00fajo","year":"2022","unstructured":"Ara\u00fajo B, Caridade-Silva R, Soares-Guedes C, Martins-Macedo J, Gomes ED, Monteiro S et al (2022) Neuroinflammation and Parkinson\u2019s disease: from neurodegeneration to therapeutic opportunities. Cells 11(18):2908. https:\/\/doi.org\/10.3390\/cells11182908","journal-title":"Cells"},{"issue":"5","key":"5800_CR71","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21051772","volume":"21","author":"L Barazzuol","year":"2020","unstructured":"Barazzuol L, Giamogante F, Brini M, Cal\u00ec T (2020) PINK1\/Parkin mediated mitophagy, Ca2+ signalling, and ER-mitochondria contacts in Parkinson\u2019s disease. Int J Mol Sci 21(5):1772. https:\/\/doi.org\/10.3390\/ijms21051772","journal-title":"Int J Mol Sci"},{"issue":"7683","key":"5800_CR72","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/d41586-017-07691-x","volume":"552","author":"S Daou","year":"2017","unstructured":"Daou S, Sicheri F (2017) Vivid views of the PINK1 protein. Nature 552(7683):38\u201339. https:\/\/doi.org\/10.1038\/d41586-017-07691-x","journal-title":"Nature"},{"issue":"5","key":"5800_CR73","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1080\/15548627.2022.2139080","volume":"19","author":"R Han","year":"2023","unstructured":"Han R, Liu Y, Li S, Li XJ, Yang W (2023) PINK1\u2013PRKN mediated mitophagy: differences between in vitro and in vivo models. Autophagy 19(5):1396\u20131405. https:\/\/doi.org\/10.1080\/15548627.2022.2139080","journal-title":"Autophagy"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-026-05800-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-026-05800-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-026-05800-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T06:25:39Z","timestamp":1773555939000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-026-05800-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":73,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["5800"],"URL":"https:\/\/doi.org\/10.1007\/s12035-026-05800-4","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"3 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Clinical trial number"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Registration details"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing\u00a0of interest"}}],"article-number":"502"}}