Epigenetic drugs targeting aberrant NF-kappaB acetylation as a potential treatment for Parkinson'...

Employer
Università degli Studi di Brescia
Location
Italy
Posted
October 12 2017
Discipline
Life Sciences, Biology
Position Type
Full Time
Organization Type
Academia

The mechanisms underlying the progressive neurodegeneration in Parkinson's disease (PD) remain unknown. NF-kappaB transcription factors are involved in the pathogenesis of several neurodegenerative diseases. Our previous findings showed that the pro-apoptotic activation of NF-kappaB in brain ischemia relies on the aberrant acetylation of RelA at Lys310 (acRelA(K310)). We reported that mice deficient for NF-kappaB/c-ReLmimic the pathological and clinical evolution of PD subjects, and display increased acRelA(K31 O) in thè basal ganglia. Our preliminary data on post mortem samples showed acRelA(K310) in the substantia nigra of PD patients. In brain ischemia, aberrant RelA acetylation is corrected by the synergistic combination of the epigenetic drugs resveratrol, an AMPactivated protein kinase-sirtuin 1 activator, and the histone deacetylase inhibitors MS-275 or valproate.



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