SpringerLink
Log in

Rosmarinic acid ameliorated oxidative stress, neuronal injuries, and mitochondrial dysfunctions mediated by polyglutamine and ɑ-synuclein in Caenorhabditis elegans models

  • Original Article
  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Numerous natural antioxidants have been developed into agents for neurodegenerative diseases (NDs) treatment. Rosmarinic acid (RA), an excellent antioxidant, exhibits neuroprotective activity, but its anti-NDs efficacy remains puzzling. Here, Caenorhabditis elegans models were employed to systematically reveal RA-mediated mechanisms in delaying NDs from diverse facets, including oxidative stress, the homeostasis of neural and protein, and mitochondrial disorders. Firstly, RA significantly inhibited reactive oxygen species accumulation, reduced peroxide malonaldehyde production, and strengthened the antioxidant defense system via increasing superoxide dismutase activity. Besides, RA reduced neuronal loss and ameliorated polyglutamine and ɑ-synuclein-mediated dyskinesia in NDs models. Further, in combination with the data and molecular docking results, RA may bind specifically to Huntington protein and ɑ-synuclein to prevent toxic protein aggregation and thus enhance proteostasis. Finally, RA ameliorated mitochondrial dysfunction including increasing adenosine triphosphate and mitochondrial membrane potential levels and rescuing mitochondrial membrane proteins’ expressions and mitochondrial structural abnormalities via regulating mitochondrial dynamics genes and improving the mitochondrial kinetic homeostasis. Thus, this study systematically revealed the RA-mediated neuroprotective mechanism and promoted RA as a promising nutritional intervention strategy to prevent NDs.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data Availability

The date and materials are available from the corresponding author upon reasonable request.

Abbreviations

ɑ-syn:

ɑ-Synuclein

AD:

Alzheimer’s disease

ATP:

Adenosine triphosphate

CaMKII:

II Ca2+/calmodulin-dependent kinase

DA:

Dopaminergic

DRP-1:

Dynamin-related protein 1

E. coli  OP50:

Escherichia coli OP50

GFP:

Green fluorescent protein

HD:

Huntington’s disease

Htt:

Huntington protein

H2DCF-DA:

2,7-Dichlorofluorescein diacetate

HSF-1:

Heat-shock factor 1

IIS:

Insulin/insulin-like growth factor 1 signaling

MDA:

Malondialdehyde

MMP:

Mitochondrial membrane potential

MAPK:

Mitogen-activated protein kinases

NDs:

Neurodegenerative diseases

Nrf2:

Mammalian NF-E2-associated factor 2

OS:

Oxidative stress

OPA1:

Optic atrophy 1 protein

PD:

Parkinson’s disease

polyQ:

Polyglutamine

PHB:

Prohibitin

RA:

Rosmarinic acid

ROS:

Reactive oxygen species

sHSPs:

Small heat-shock proteins

TOM-7:

Translocase of the outer mitochondrial membrane 7

YFP:

Yellow fluorescent protein

References

  1. Elfawy HA, Das B (2019) Crosstalk between mitochondrial dysfunction, oxidative stress, and age related neurodegenerative disease: etiologies and therapeutic strategies. Life Sci 218:165–184. https://doi.org/10.1016/j.lfs.2018.12.029

    Article  CAS  PubMed  Google Scholar 

  2. Van Pelt KM, Truttmann MC (2020) Caenorhabditis elegans as a model system for studying aging-associated neurodegenerative diseases. Transl Med Aging 4:60–72. https://doi.org/10.1016/j.tma.2020.05.001

    Article  PubMed  PubMed Central  Google Scholar 

  3. Fan HC, Ho LI, Chi CS, Chen SJ, Peng GS, Chan TM, Lin SZ, Harn HJ (2014) Polyglutamine (PolyQ) diseases: genetics to treatments. Cell Transplant 23(4–5):441–458. https://doi.org/10.3727/096368914X678454

    Article  PubMed  Google Scholar 

  4. Boasquivis PF, Silva G, Paiva FA, Cavalcanti RM, Nunez CV, Oliveira RD (2018) Guarana (Paullinia cupana) extract protects Caenorhabditis elegans models for Alzheimer disease and Huntington disease through activation of antioxidant and protein degradation pathways. Oxid Med Cell Longev 2018:9241308. https://doi.org/10.1155/2018/9241308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cooper JF, Van Raamsdonk JM (2018) Modeling Parkinson’s disease in C. elegans. J Parkinson’s Dis 8(1):17–32

    Article  CAS  Google Scholar 

  6. Di Rosa G, Brunetti G, Scuto M, Trovato Salinaro A, Calabrese EJ, Crea R, Schmitz-Linneweber C, Calabrese V et al (2020) Healthspan enhancement by olive polyphenols in C. elegans wild type and Parkinson’s models. Int J Mol Sci 21(11):3893. https://doi.org/10.3390/ijms21113893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Amor S, Puentes F, Baker D, Van Der Valk P (2010) Inflammation in neurodegenerative diseases. Immunology 129(2):154–169. https://doi.org/10.1111/j.1365-2567.2009.03225.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Taylor JP, Hardy J, Fischbeck KH (2002) Toxic proteins in neurodegenerative disease. Science 296(5575):1991–1995. https://doi.org/10.1126/science.1067122

    Article  CAS  PubMed  Google Scholar 

  9. Chung CG, Lee H, Lee SB (2018) Mechanisms of protein toxicity in neurodegenerative diseases. Cell Mol Life Sci 75(17):3159–3180. https://doi.org/10.1007/s00018-018-2854-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443(7113):787–795. https://doi.org/10.1038/nature05292

    Article  CAS  PubMed  Google Scholar 

  11. Zhao Y, Zhao B (2013) Oxidative stress and the pathogenesis of Alzheimer’s disease. Oxid Med Cell Longev 2013:1–10. https://doi.org/10.1155/2013/316523

    Article  CAS  Google Scholar 

  12. Romero-Márquez JM, Navarro-Hortal MD, Jiménez-Trigo V, Vera-Ramírez L, Forbes-Hernández TJ, Esteban-Muñoz A, Giampieri F, Bullón P et al (2022) An oleuropein rich-olive (Olea europaea L.) leaf extract reduces β-amyloid and tau proteotoxicity through regulation of oxidative- and heat shock-stress responses in Caenorhabditis elegans. Food Chem Toxicol 162:112914

    Article  PubMed  Google Scholar 

  13. Silva RFM, Pogačnik L (2020) Polyphenols from food and natural products: neuroprotection and safety. Antioxidants (Basel) 9(1):61. https://doi.org/10.3390/antiox9010061

    Article  CAS  PubMed  Google Scholar 

  14. Dhouafli Z, Cuanalo-Contreras K, Hayouni EA, Mays CE, Soto C, Moreno-Gonzalez I (2018) Inhibition of protein misfolding and aggregation by natural phenolic compounds. Cell Mol Life Sci 75(19):3521–3538. https://doi.org/10.1007/s00018-018-2872-2

    Article  CAS  PubMed  Google Scholar 

  15. Yamamoto S, Kayama T, Noguchi-Shinohara M, Hamaguchi T, Yamada M, Abe K, Kobayashi S (2021) Rosmarinic acid suppresses tau phosphorylation and cognitive decline by downregulating the JNK signaling pathway. NPJ Sci Food 5(1):1. https://doi.org/10.1038/s41538-021-00084-5

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lin C, **ao J, ** Y, Zhang X, Zhong Q, Zheng H, Cao Y, Chen Y (2019) Rosmarinic acid improved antioxidant properties and healthspan via the IIS and MAPK pathways in Caenorhabditis elegans. BioFactors 45(5):774–787. https://doi.org/10.1002/biof.1536

    Article  CAS  PubMed  Google Scholar 

  17. Lee HJ, Cho H, Park E, Kim S, Lee S, Kim C, Kim DK, Kim S et al (2008) Rosmarinic acid protects human dopaminergic neuronal cells against hydrogen peroxide-induced apoptosis. Toxicology 250(2–3):109–115. https://doi.org/10.1016/j.tox.2008.06.010

    Article  CAS  PubMed  Google Scholar 

  18. Thingore C, Kshirsagar V, Juvekar A (2021) Amelioration of oxidative stress and neuroinflammation in lipopolysaccharide-induced memory impairment using Rosmarinic acid in mice. Metab Brain Dis 36(2):299–313. https://doi.org/10.1007/s11011-020-00629-9

    Article  CAS  PubMed  Google Scholar 

  19. Wang J, Xu H, Jiang H, Du X, Sun P, **e J (2012) Neurorescue effect of rosmarinic acid on 6-hydroxydopamine-lesioned nigral dopamine neurons in rat model of Parkinson’s disease. J Mol Neurosci 47(1):113–119. https://doi.org/10.1007/s12031-011-9693-1

    Article  CAS  PubMed  Google Scholar 

  20. Markaki M, Tavernarakis N (2020) Caenorhabditis elegans as a model system for human diseases. Curr Opin Biotechnol 63:118–125. https://doi.org/10.1016/j.copbio.2019.12.011

    Article  CAS  PubMed  Google Scholar 

  21. Vaccaro A, Tauffenberger A, Aggad D, Rouleau G, Drapeau P, Parker JA (2012) Mutant TDP-43 and FUS cause age-dependent paralysis and neurodegeneration in C. elegans. PLoS ONE 7(2):e31321. https://doi.org/10.1371/journal.pone.0031321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Dostal V, Link CD (2010) Assaying β-amyloid toxicity using a transgenic C. elegans model. J Vis Exp 9(44):e2252

    Google Scholar 

  23. Ma X, Li J, Cui X, Li F, Wang Z (2019) Dietary supplementation with peptides from sesame cake protect Caenorhabditis elegans from polyglutamine-induced toxicity. J Funct Foods 54:199–210. https://doi.org/10.1016/j.jff.2019.01.002

    Article  CAS  Google Scholar 

  24. Morley JF, Brignull HR, Weyers JJ, Morimoto RI (2002) The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans. Proc Natl Acad Sci 99(16):10417–10422. https://doi.org/10.1073/pnas.152161099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chen Y, Qin Q, Zhao W, Luo D, Huang Y, Liu G, Kuang Y, Cao Y et al (2022) Carnosol reduced pathogenic protein aggregation and cognitive impairment in neurodegenerative diseases models via improving proteostasis and ameliorating mitochondrial disorders. J Agric Food Chem 70(34):10490–10505. https://doi.org/10.1021/acs.jafc.2c02665

    Article  CAS  PubMed  Google Scholar 

  26. Zeng XS, Geng WS, Jia JJ (2018) Neurotoxin-induced animal models of Parkinson disease: pathogenic mechanism and assessment. ASN Neuro 10:1663354718. https://doi.org/10.1177/1759091418777438

    Article  CAS  Google Scholar 

  27. Tucci ML, Harrington AJ, Caldwell GA, Caldwell KA (2011) Modeling dopamine neuron degeneration in Caenorhabditis elegans. Methods Mol Biol 793:129–148. https://doi.org/10.1007/978-1-61779-328-8_9

    Article  CAS  PubMed  Google Scholar 

  28. Muhammad F, Liu Y, Wang N, Zhao L, Zhou Y, Yang H, Li H (2022) Anti-synuclein toxicity and anti-neurodegenerative role of chrysin in transgenic Caenorhabditis elegans models of Parkinson’s disease. ACS Chem Neurosci 13(4):442–453. https://doi.org/10.1021/acschemneuro.1c00548

    Article  CAS  PubMed  Google Scholar 

  29. Roussel N, Sprenger J, Tappan SJ, Glaser JR (2015) Robust tracking and quantification of C. elegans body shape and locomotion through coiling, entanglement, and omega bends. Worm 3(4):e982437. https://doi.org/10.4161/21624054.2014.982437

  30. Sun J, Roy S (2021) Gene-based therapies for neurodegenerative diseases. Nat Neurosci 24(3):297–311. https://doi.org/10.1038/s41593-020-00778-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Pohl F, Kong TLP (2018) The potential use of plant natural products and plant extracts with antioxidant properties for the prevention/treatment of neurodegenerative diseases: in vitro, in vivo and clinical trials. Molecules 23(12):3283. https://doi.org/10.3390/molecules23123283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chia SJ, Tan E, Chao Y (2020) Historical perspective: models of Parkinson’s disease. Int J Mol Sci 21(7):2464. https://doi.org/10.3390/ijms21072464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Khanna A, Sellegounder D, Kumar J, Chamoli M, Vargas M, Chinta SJ, Rane A, Nelson C et al (2021) Trimethylamine modulates dauer formation, neurodegeneration, and lifespan throughtyra-3/daf-11 signaling in Caenorhabditis elegans. Aging Cell 20(5):e13351. https://doi.org/10.1111/acel.13351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rekatsina M, Paladini A, Piroli A, Zis P, Pergolizzi JV, Varrassi G (2020) Pathophysiology and therapeutic perspectives of oxidative stress and neurodegenerative diseases: a narrative review. Adv Ther 37(1):113–139. https://doi.org/10.1007/s12325-019-01148-5

    Article  PubMed  Google Scholar 

  35. Sanyal I, Bandyopadhyay SK, Banerjee TK, Mukherjee SC, Chakraborty DP, Ray BC, Rao VR (2009) Plasma levels of lipid peroxides in patients with Parkinson’s disease. Eur Rev Med Pharmacol Sci 13(2):129–132

    CAS  PubMed  Google Scholar 

  36. Dib M, Garrel C, Favier A, Robin V, Desnuelle C (2002) Can malondialdehyde be used as a biological marker of progression in neurodegenerative disease? J Neurol 249(4):367–374. https://doi.org/10.1007/s004150200025

    Article  CAS  PubMed  Google Scholar 

  37. Ayala A, Muñoz MF, Argüelles S, Ramana KV (2014) Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014:360431–360438. https://doi.org/10.1155/2014/360438

    Article  CAS  Google Scholar 

  38. Chen CM, Wu YR, Cheng ML, Liu JL, Lee YM, Lee PW, Soong BW, Chiu DT (2007) Increased oxidative damage and mitochondrial abnormalities in the peripheral blood of Huntington’s disease patients. Biochem Biophys Res Commun 359(2):335–340. https://doi.org/10.1016/j.bbrc.2007.05.093

    Article  CAS  PubMed  Google Scholar 

  39. Schuessel K, Schäfer S, Bayer TA, Czech C, Pradier L, Müller-Spahn F, Müller WE, Eckert A (2005) Impaired Cu/Zn-SOD activity contributes to increased oxidative damage in APP transgenic mice. Neurobiol Dis 18(1):89–99. https://doi.org/10.1016/j.nbd.2004.09.003

    Article  CAS  PubMed  Google Scholar 

  40. Chi H, Chang H, Sang T (2018) Neuronal cell death mechanisms in major neurodegenerative diseases. Int J Mol Sci 19(10):3082. https://doi.org/10.3390/ijms19103082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Anjaneyulu J, R V, Godbole A (2020) Differential effect of Ayurvedic nootropics on C. elegans models of Parkinson’s disease. J Ayurveda Integr Med 11(4):440–447. https://doi.org/10.1016/j.jaim.2020.07.006

  42. Cordeiro LM, Machado ML, Da SA, Obetine BF, Da ST, Soares F, Arantes LP (2020) Rutin protects Huntington’s disease through the insulin/IGF1 (IIS) signaling pathway and autophagy activity: Study in Caenorhabditis elegans model. Food Chem Toxicol 141:111323. https://doi.org/10.1016/j.fct.2020.111323

    Article  CAS  PubMed  Google Scholar 

  43. Inestrosa NC, Varela-Nallar L (2014) Wnt signaling in the nervous system and in Alzheimer’s disease. J Mol Cell Biol 6(1):64–74. https://doi.org/10.1093/jmcb/mjt051

    Article  PubMed  Google Scholar 

  44. Rosso SB, Inestrosa NC (2013) WNT signaling in neuronal maturation and synaptogenesis. Front Cell Neurosci 7:103. https://doi.org/10.3389/fncel.2013.00103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Maro GS, Klassen MP, Shen K (2009) A β-catenin-dependent Wnt pathway mediates anteroposterior axon guidance in C. elegans motor neurons. PLoS ONE 4(3):e4690. https://doi.org/10.1371/journal.pone.0004690

  46. Serafino A, Sferrazza G, Colini Baldeschi A, Nicotera G, Andreola F, Pittaluga E, Pierimarchi P (2016) Develo** drugs that target the Wnt pathway: recent approaches in cancer and neurodegenerative diseases. Expert Opin Drug Discov 12(2):169–186. https://doi.org/10.1080/17460441.2017.1271321

    Article  CAS  PubMed  Google Scholar 

  47. Purro SA, Galli S, Salinas PC (2014) Dysfunction of Wnt signaling and synaptic disassembly in neurodegenerative diseases. J Mol Cell Biol 6(1):75–80. https://doi.org/10.1093/jmcb/mjt049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Gao J, Liao Y, Qiu M, Shen W (2021) Wnt/beta-catenin signaling in neural stem cell homeostasis and neurological diseases. Neuroscientist 27(1):58–72. https://doi.org/10.1177/1073858420914509

    Article  CAS  PubMed  Google Scholar 

  49. Arredondo SB, Valenzuela-Bezanilla D, Mardones MD, Varela-Nallar L (2020) Role of Wnt signaling in adult hippocampal neurogenesis in health and disease. Front Cell Dev Biol 8:860. https://doi.org/10.3389/fcell.2020.00860

    Article  PubMed  PubMed Central  Google Scholar 

  50. Maleki Dana P, Sadoughi F, Mansournia MA, Mirzaei H, Asemi Z, Yousefi B (2021) Targeting Wnt signaling pathway by polyphenols: implication for aging and age-related diseases. Biogerontology (Dordrecht) 22(5):479–494. https://doi.org/10.1007/s10522-021-09934-x

    Article  CAS  Google Scholar 

  51. Inestrosa NC, Toledo EM (2008) The role of Wnt signaling in neuronal dysfunction in Alzheimer’s disease. Mol Neurodegener 3(1):9. https://doi.org/10.1186/1750-1326-3-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kapoor ANDA (2020) Role of Notch signaling in neurovascular aging and Alzheimer’s disease. Seminars in Cell & Developmental Biology Elsevier. doi:https://doi.org/10.1016/j.semcdb.2020.12.011

  53. Woo H, Park J, Gwon A, Arumugam TV, Jo D (2009) Alzheimer’s disease and Notch signaling. Biochem Biophys Res Commun 390(4):1093–1097. https://doi.org/10.1016/j.bbrc.2009.10.093

    Article  CAS  PubMed  Google Scholar 

  54. Son HG, Altintas O, Kim EJE, Kwon S, Lee SJV (2019) Age-dependent changes and biomarkers of aging in Caenorhabditis elegans. Aging Cell 18(2):e12853. https://doi.org/10.1111/acel.12853

  55. Alves LGA, Winter PB, Ferreira LN, Brielmann RM, Morimoto RI, Amaral LAN (2017) Long-range correlations and fractal dynamics in C. elegans: Changes with aging and stress. Phys Rev E 96(2):022417. https://doi.org/10.1103/PhysRevE.96.022417

  56. Munoz-Lobato F, Rodriguez-Palero MJ, Naranjo-Galindo FJ, Shephard F, Gaffney CJ, Szewczyk NJ, Hamamichi S, Caldwell KA et al (2014) Protective role of DNJ-27 / ERdj5 in Caenorhabditis elegans models of human neurodegenerative diseases. Antioxid Redox Signal 20(2):217–235. https://doi.org/10.1089/ars.2012.5051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Burke KA, Hensal KM, Umbaugh CS, Chaibva M, Legleiter J (2013) Huntingtin disrupts lipid bilayers in a polyQ-length dependent manner. Biochimica et Biophysica Acta (BBA)-Biomembrane 1828(8):1953–1961. https://doi.org/10.1016/j.bbamem.2013.04.025

    Article  CAS  Google Scholar 

  58. Bose A, Beal MF (2016) Mitochondrial dysfunction in Parkinson’s disease. J Neurochem 139(S1):216–231. https://doi.org/10.1111/jnc.13731

    Article  CAS  PubMed  Google Scholar 

  59. Kotler SA, Tugarinov V, Schmidt T, Ceccon A, Libich DS, Ghirlando R, Schwieters CD, Clore GM (2019) Probing initial transient oligomerization events facilitating Huntingtin fibril nucleation at atomic resolution by relaxation-based NMR. Proc Natl Acad Sci U S A 116(9):3562–3571. https://doi.org/10.1073/pnas.1821216116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Salveson PJ, Spencer RK, Nowick JS (2016) X-ray crystallographic structure of oligomers formed by a toxic β-hairpin derived from α-synuclein: trimers and higher-order oligomers. J Am Chem Soc 138(13):4458–4467. https://doi.org/10.1021/jacs.5b13261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Yamashita H, Tomoshige S, Nomura S, Ohgane K, Hashimoto Y, Ishikawa M (2020) Application of protein knockdown strategy targeting β-sheet structure to multiple disease-associated polyglutamine proteins. Bioorg Med Chem 28(1):115175. https://doi.org/10.1016/j.bmc.2019.115175

    Article  CAS  PubMed  Google Scholar 

  62. Fujiwara K, Toda H, Ikeguchi M (2012) Dependence of alpha-helical and beta-sheet amino acid propensities on the overall protein fold type. BMC Struct Biol 12(1):18. https://doi.org/10.1186/1472-6807-12-18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Wanker EE (2000) Protein aggregation in Huntington’s and Parkinson’s disease: implications for therapy. Mol Med Today 6(10):387–391. https://doi.org/10.1016/S1357-4310(00)01761-5

    Article  CAS  PubMed  Google Scholar 

  64. Cohen E, Dillin A (2008) The insulin paradox: aging, proteotoxicity and neurodegeneration. Nat Rev Neurosci 9(10):759–767. https://doi.org/10.1038/nrn2474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Knight AL, Yan X, Hamamichi S, Ajjuri RR, Mazzulli JR, Zhang MW, Daigle JG, Zhang S et al (2014) The glycolytic enzyme, GPI, is a functionally conserved modifier of dopaminergic neurodegeneration in Parkinson’s models. Cell Metab 20(1):145–157. https://doi.org/10.1016/j.cmet.2014.04.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Mukhopadhyay A, Oh SW, Tissenbaum HA (2006) Worming pathways to and from DAF-16/FOXO. Exp Gerontol 41(10):928–934. https://doi.org/10.1016/j.exger.2006.05.020

    Article  CAS  PubMed  Google Scholar 

  67. Zhang L, Jie G, Zhang J, Zhao B (2009) Significant longevity-extending effects of EGCG on Caenorhabditis elegans under stress. Free Radic Biol Med 46(3):414–421. https://doi.org/10.1016/j.freeradbiomed.2008.10.041

    Article  CAS  PubMed  Google Scholar 

  68. Kourtis N, Nikoletopoulou V, Tavernarakis N (2012) Small heat-shock proteins protect from heat-stroke-associated neurodegeneration. Nature 490(7419):213–218. https://doi.org/10.1038/nature11417

    Article  CAS  PubMed  Google Scholar 

  69. Koga H, Kaushik S, Cuervo AM (2011) Protein homeostasis and aging: the importance of exquisite quality control. Ageing Res Rev 10(2):205–215. https://doi.org/10.1016/j.arr.2010.02.001

    Article  CAS  PubMed  Google Scholar 

  70. Neef DW, Jaeger AM, Thiele DJ (2011) Heat shock transcription factor 1 as a therapeutic target in neurodegenerative diseases. Nat Rev Drug Discov 10(12):930–944. https://doi.org/10.1038/nrd3453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Hartl FU, Bracher A, Hayer-Hartl M (2011) Molecular chaperones in protein folding and proteostasis. Nature 475(7356):324–332. https://doi.org/10.1038/nature10317

    Article  CAS  PubMed  Google Scholar 

  72. Govindan S, Amirthalingam M, Duraisamy K, Govindhan T, Sundararaj N, Palanisamy S (2018) Phytochemicals-induced hormesis protects Caenorhabditis elegans against alpha-synuclein protein aggregation and stress through modulating HSF-1 and SKN-1/Nrf2 signaling pathways. Biomed Pharmacother 102:812–822. https://doi.org/10.1016/j.biopha.2018.03.128

    Article  CAS  PubMed  Google Scholar 

  73. Fonte V, Kipp DR, Yerg JR, Merin D, Forrestal M, Wagner E, Roberts CM, Link CD (2008) Suppression of in vivo beta-amyloid peptide toxicity by overexpression of the HSP-16.2 small chaperone protein. J Biol Chem 283(2):784–791. https://doi.org/10.1074/jbc.M703339200

    Article  CAS  PubMed  Google Scholar 

  74. Corrêa SAL, Eales KL (2012) The role of p38 MAPK and its substrates in neuronal plasticity and neurodegenerative disease. J Signal Transduction 2012:1–12. https://doi.org/10.1155/2012/649079

    Article  CAS  Google Scholar 

  75. Yu CW, Wei CC, Liao VHC (2013) Curcumin-mediated oxidative stress resistance in Caenorhabditis elegans is modulated byage-1, akt-1, pdk-1, osr-1, unc-43, sek-1, skn-1, sir-2.1, and mev-1. Free Radic Res 48(3):371–379. https://doi.org/10.3109/10715762.2013.872779

  76. Pietsch K, Saul N, Menzel R, Stürzenbaum SR, Steinberg CEW (2009) Quercetin mediated lifespan extension in Caenorhabditis elegans is modulated by age-1, daf-2, sek-1 and unc-43. Biogerontology 10(5):565–578. https://doi.org/10.1007/s10522-008-9199-6

    Article  CAS  PubMed  Google Scholar 

  77. Jodeiri Farshbaf M, Ghaedi K (2017) Huntington’s disease and mitochondria. Neurotox Res 32(3):518–529. https://doi.org/10.1007/s12640-017-9766-1

    Article  CAS  PubMed  Google Scholar 

  78. Brookes PS, Yoon Y, Robotham JL, Anders MW, Sheu S (2004) Calcium, ATP, and ROS: a mitochondrial love-hate triangle. Am J Physiol Cell Physiol 287(4):C817–C833. https://doi.org/10.1152/ajpcell.00139.2004

    Article  CAS  PubMed  Google Scholar 

  79. Wang X, Su B, Zheng L, Perry G, Smith MA, Zhu X (2009) The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer’s disease. J Neurochem 109(s1):153–159. https://doi.org/10.1111/j.1471-4159.2009.05867.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Waizenegger T, Schmitt S, Zivkovic J, Neupert W, Rapaport D (2005) Mim1, a protein required for the assembly of the TOM complex of mitochondria. EMBO Rep 6(1):57–62. https://doi.org/10.1038/sj.embor.7400318

    Article  CAS  PubMed  Google Scholar 

  81. Acín-Pérez R, Fernández-Silva P, Peleato ML, Pérez-Martos A, Enriquez JA (2008) Respiratory active mitochondrial supercomplexes. Mol Cell 32(4):529–539. https://doi.org/10.1016/j.molcel.2008.10.021

    Article  CAS  PubMed  Google Scholar 

  82. Signorile A, Sgaramella G, Bellomo F, De Rasmo D (2019) Prohibitins: a critical role in mitochondrial functions and implication in diseases. Cells (Basel, Switzerland) 8(1):71. https://doi.org/10.3390/cells8010071

    Article  CAS  Google Scholar 

  83. Merkwirth C, Martinelli P, Korwitz A, Morbin M, Brönneke HS, Jordan SD, Rugarli EI, Langer T (2012) Loss of prohibitin membrane scaffolds impairs mitochondrial architecture and leads to tau hyperphosphorylation and neurodegeneration. PLoS Genet 8(11):e1003021. https://doi.org/10.1371/journal.pgen.1003021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Ye J, Li J, **a R, Zhou M, Yu L (2015) Prohibitin protects proximal tubule epithelial cells against oxidative injury through mitochondrial pathways. Free Radic Res 49(11):1393–1403. https://doi.org/10.3109/10715762.2015.1075654

    Article  CAS  PubMed  Google Scholar 

  85. Lee H, Smith SB, Yoon Y (2017) The short variant of the mitochondrial dynamin OPA1 maintains mitochondrial energetics and cristae structure. J Biol Chem 292(17):7115–7130. https://doi.org/10.1074/jbc.M116.762567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Palmer CS, Osellame LD, Stojanovski D, Ryan MT (2011) The regulation of mitochondrial morphology: intricate mechanisms and dynamic machinery. Cell Signal 23(10):1534–1545. https://doi.org/10.1016/j.cellsig.2011.05.021

    Article  CAS  PubMed  Google Scholar 

  87. Byrne JJ, Soh MS, Chandhok G, Vijayaraghavan T, Teoh J, Crawford S, Cobham AE, Yapa NMB et al (2019) Disruption of mitochondrial dynamics affects behaviour and lifespan in Caenorhabditis elegans. Cell Mol Life Sci 76(10):1967–1985. https://doi.org/10.1007/s00018-019-03024-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Starr DA, Han M (2002) Role of ANC-1 in tethering nuclei to the actin cytoskeleton. Science 298(5592):406–409. https://doi.org/10.1126/science.1075119

    Article  CAS  PubMed  Google Scholar 

  89. Tsang WY, Lemire BD (2003) Mitochondrial ATP synthase controls larval development cell nonautonomously in Caenorhabditis elegans. Dev Dyn 226(4):719–726. https://doi.org/10.1002/dvdy.10272

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

C. elegans strains were provided by the Caenorhabditis Genetics Center at University of Minnesota.

Funding

This research was supported by the General project of the Natural Science Foundation of Guangdong Province, China (2022A1515010907; 2023A1515011266) and the Action for Revitalizing Seed Industry and Promoting Agriculture through Science and Technology (2023LZ04).

Author information

Authors and Affiliations

  1. Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, 510640, Guangdong, China

    Yun Chen, Ruina Xu, Qiaoxing Liu, Yanting Zeng, Weitian Chen, Yongfa Liu, Yong Cao, Guo Liu & Yunjiao Chen

  2. Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510640, Guangdong, China

    Yun Chen, Ruina Xu, Qiaoxing Liu, Yanting Zeng, Weitian Chen, Yongfa Liu, Yong Cao, Guo Liu & Yunjiao Chen

  3. College of Light Industry and Food, Zhongkai University of Agriculture and Engineering, Guangzhou, 510225, Guangdong, China

    Guo Liu

Authors
  1. Yun Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ruina Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qiaoxing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yanting Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Weitian Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yongfa Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yong Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Guo Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yunjiao Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Yun.C.: formal analysis, investigation, writing-original draft, writing-review and editing, data curation. R.X.: investigation, data curation, writing-review and editing. Q.L.: investigation, writing-original draft, visualization, data curation. Y.Z.: project administration, visualization, investigation. W.C.: data curation, visualization, investigation. Y.L.: project administration, visualization, investigation. Y.Cao: conceptualization, writing-review and editing. G.L.: methodology, writing-review and editing, conception. Yunj.C.: conceptualization, methodology, writing-review and editing, funding acquisition.

Corresponding authors

Correspondence to Guo Liu or Yunjiao Chen.

Ethics declarations

Ethics Approval

Not applicable.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Yun Chen and Ruina Xu should be considered joint first authors.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 36.4 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, Y., Xu, R., Liu, Q. et al. Rosmarinic acid ameliorated oxidative stress, neuronal injuries, and mitochondrial dysfunctions mediated by polyglutamine and ɑ-synuclein in Caenorhabditis elegans models. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04206-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12035-024-04206-4

Keywords

Search

Navigation