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

Int J Mol Sci

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

Published: November 2022

AI Article Synopsis

  • Parkinson's disease (PD) is a rapidly growing movement disorder with no current disease-modifying therapy available.
  • Mildly elevated levels of unconjugated bilirubin (UCB) have shown protective effects against certain diseases due to their antioxidant and anti-inflammatory properties.
  • In a PD model study, low concentrations of UCB effectively protected dopaminergic neurons from damage, with inflammation—especially involving tumor necrosis factor alpha (TNF-α)—being critical to this protective effect.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693357PMC
http://dx.doi.org/10.3390/ijms232214276DOI Listing

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