Tauroursodeoxycholic acid (TUDCA) is neuroprotective in a chronic mouse model of Parkinson’s disease

Elvis Cuevas, Susan Burks, James Raymick, Bonnie Robinson, Nancy P. Gómez-Crisóstomo, Claudia Escudero-Lourdes, Aida G.Guzman Lopez, Srinivasulu Chigurupati, Joseph Hanig, Sherry A. Ferguson, Sumit Sarkar

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Objective: Parkinson’s disease (PD) is a progressive motor disease of unknown etiology. Although neuroprotective ability of endogenous bile acid, tauroursodeoxycholic acid (TUDCA), shown in various diseases, including an acute model of PD,the potential therapeutic role of TUDCA in progressive models of PD that exhibit all aspects of PD has not been elucidated. In the present study, mice were assigned to one of four treatment groups: (1) Probenecid (PROB); (2) TUDCA, (3) MPTP + PROB (MPTPp); and (3) TUDCA + MPTPp. Methods: Markers for dopaminergic function, neuroinflammation, oxidative stress and autophagy were assessed using high performance liquid chromatography (HPLC), immunohistochemistry (IHC) and western blot (WB) methods. Locomotion was measured before and after treatments. Results: MPTPp decreased the expression of dopamine transporters (DAT) and tyrosine hydroxylase (TH), indicating dopaminergic damage, and induced microglial and astroglial activation as demonstrated by IHC analysis. MPTPp also decreased DA and its metabolites as demonstrated by HPLC analysis. Further, MPTPp-induced protein oxidation; increased LAMP-1 expression indicated autophagy and the promotion of alpha-synuclein (α-SYN) aggregation. Discussion: Pretreatment with TUDCA protected against dopaminergic neuronal damage, prevented the microglial and astroglial activation, as well as the DA and DOPAC reductions caused by MPTPp. TUDCA by itself did not produce any significant change, with data similar to the negative control group. Pretreatment with TUDCA prevented protein oxidation and autophagy, in addition to inhibiting α-SYN aggregation. Although TUDCA pretreatment did not significantly affect locomotion, only acute treatment effects were measured, indicating more extensive assessments may be necessary to reveal potential therapeutic effects on behavior. Together, these results suggest that autophagy may be involved in the progression of PD and that TUDCA may attenuate these effects. The efficacy of TUDCA as a novel therapy in patients with PD clearly warrants further study.

Original languageEnglish (US)
Pages (from-to)1374-1391
Number of pages18
JournalNutritional Neuroscience
Volume25
Issue number7
DOIs
StatePublished - 2022
Externally publishedYes

Keywords

  • 1-methyl-4-phenyl-1-2- 3-6-tetrahydropyridine (MPTP)
  • Parkinson’s disease
  • alpha synuclein
  • autophagy
  • dopamine transporter
  • dopaminergic neurons
  • lysosome-associated membrane protein 1 (LAMP-1)
  • tauroursodeoxycholic acid
  • tyrosine hydroxylase

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Neuroscience(all)
  • Nutrition and Dietetics

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