BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease with 
characteristics and symptoms that are well defined. Nevertheless, its aetiology 
remains unknown. PD is characterized by the presence of Lewy bodies inside 
neurons. α-Synuclein (α-syn) is a soluble protein present in the pre-synaptic 
terminal of neurons. Evidence suggests that α-syn has a fundamental role in PD 
pathogenesis, given that it is an important component of Lewy bodies localized 
in the dopaminergic neurons of PD patients.
METHODS: In the present study, we investigated the influence of wild type (WT) 
and A30P α-syn overexpression on neuroblastoma SH-SY5Y toxicity induced by the 
conditioned medium (CM) from primary cultures of glia challenged with 
lipopolysaccharide (LPS) from Escherichia coli.
RESULTS: We observed that SH-SY5Y cells transduced with α-syn (WT or A30P) and 
treated with CM from LPS-activated glia cells show evidence of cell death, which 
is not reverted by NF-κB inhibition by sodium salicylate or by blockage of P50 
(NF-κB subunit). Furthermore, the expression of A30P α-syn in neuroblastoma 
SH-SY5Y decreases the cell death triggered by the CM of activated glia versus WT 
α-syn or control group. This effect of A30P α-syn may be due to the low 
MAPK42/44 phosphorylation. This finding is substantiated by MEK1 inhibition by 
PD98059, decreasing LDH release by CM in SH-SY5Y cells.
CONCLUSION: Our results suggest that SH-SY5Y cells transduced with α-syn (WT or 
A30P) and treated with CM from LPS-activated glia cells show cell death, which 
is not reverted by NF-κB blockage. Additionally, the expression of A30P α-syn on 
neuroblastoma SH-SY5Y leads to decreased cell death triggered by the CM of 
activated glia, when compared to WT α-syn or control group. The mechanism 
underlying this process remains to be completely elucidated, but the present 
data suggest that MAPK42/44 phosphorylation plays an important role in this 
process.
PROSPERO: CRD42015020829.