Bilirubin Prevents the TH+ Dopaminergic Neuron Loss in a Parkinson's Disease Model by Acting on TNF-α.
Int J Mol Sci
; 23(22)2022 Nov 17.
Article
em En
| MEDLINE
| ID: mdl-36430754
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Neurônios Dopaminérgicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Itália