Bilirubin Prevents the TH+ Dopaminergic Neuron Loss in a Parkinson’s Disease Model by Acting on TNF-α

Jayanti, Sri; Moretti, Rita; Tiribelli, Claudio; Gazzin, Silvia

doi:10.3390/ijms232214276

Open AccessArticle

Bilirubin Prevents the TH⁺ Dopaminergic Neuron Loss in a Parkinson’s Disease Model by Acting on TNF-α

¹

The Liver-Brain Unit “Rita-Moretti”, Fondazione Italiana Fegato-Onlus, Bldg. Q, AREA Science Park, ss14, Km 163.5, Basovizza, 34149 Trieste, Italy

²

Faculty of Medicine, University of Hasanuddin, Makassar 90245, Indonesia

³

Molecular Biomedicine Ph.D. Program, Department of Life Sciences, University of Trieste, 34127 Trieste, Italy

⁴

Neurology Clinic, Department of Medical, Surgical and Health Sciences, University of Trieste, 34139 Trieste, Italy

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2022, 23(22), 14276; https://doi.org/10.3390/ijms232214276

Submission received: 22 September 2022 / Revised: 9 November 2022 / Accepted: 16 November 2022 / Published: 17 November 2022

(This article belongs to the Special Issue Bilirubin)

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Abstract

Parkinson’s disease (PD), the fastest-growing movement disorder, is still challenged by the unavailability of disease-modifying therapy. Mildly elevated levels of unconjugated bilirubin (UCB, PubChem CID 5280352) have been shown to be protective against several extra-CNS diseases, and the effect is attributed to its well-known anti-oxidant and anti-inflammatory capability. We explored the neuroprotective effect of low concentrations of UCB (from 0.5 to 4 µM) in our PD model based on organotypic brain cultures of substantia nigra (OBCs-SN) challenged with a low dose of rotenone (Rot). UCB at 0.5 and 1 µM fully protects against the loss of TH⁺ (dopaminergic) neurons (DOPAn). The alteration in oxidative stress is involved in TH⁺ positive neuron demise induced by Rot, but is not the key player in UCB-conferred protection. On the contrary, inflammation, specifically tumor necrosis factor alpha (TNF-α), was found to be the key to UCB protection against DOPAn sufferance. Further work will be needed to introduce the use of UCB into clinical settings, but determining that TNF-α plays a key role in PD may be crucial in designing therapeutic options.

Keywords: tumor necrosis factor-alpha; neurodegenerative diseases; disease-modifying therapy; inflammation; redox; free bilirubin

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MDPI and ACS Style

Jayanti, S.; Moretti, R.; Tiribelli, C.; Gazzin, S. Bilirubin Prevents the TH⁺ Dopaminergic Neuron Loss in a Parkinson’s Disease Model by Acting on TNF-α. Int. J. Mol. Sci. 2022, 23, 14276. https://doi.org/10.3390/ijms232214276

AMA Style

Jayanti S, Moretti R, Tiribelli C, Gazzin S. Bilirubin Prevents the TH⁺ Dopaminergic Neuron Loss in a Parkinson’s Disease Model by Acting on TNF-α. International Journal of Molecular Sciences. 2022; 23(22):14276. https://doi.org/10.3390/ijms232214276

Chicago/Turabian Style

Jayanti, Sri, Rita Moretti, Claudio Tiribelli, and Silvia Gazzin. 2022. "Bilirubin Prevents the TH⁺ Dopaminergic Neuron Loss in a Parkinson’s Disease Model by Acting on TNF-α" International Journal of Molecular Sciences 23, no. 22: 14276. https://doi.org/10.3390/ijms232214276

APA Style

Jayanti, S., Moretti, R., Tiribelli, C., & Gazzin, S. (2022). Bilirubin Prevents the TH⁺ Dopaminergic Neuron Loss in a Parkinson’s Disease Model by Acting on TNF-α. International Journal of Molecular Sciences, 23(22), 14276. https://doi.org/10.3390/ijms232214276

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Bilirubin Prevents the TH⁺ Dopaminergic Neuron Loss in a Parkinson’s Disease Model by Acting on TNF-α

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