title: Epigenetic engineering to reverse the Parkinson's expression state.
abstract: Nature, initiation and ensuing cellular propagation mode of sporadic Parkinson's disease (comprising over 90% of all Parkinson's cases) remain open research questions. Accordingly, so does the best therapeutic avenue for addressing this debilitating disease that today affects an estimated 7-10 million people worldwide. Recently, we argued that sporadic Parkinson's be fundamentally characterized as a pathological deviation from normality in the expression program of a cell, the PD-state. Further, we suggested this generic cell state (not restricted to neurons) could be epigenetically locked-in. This raises the theoretical possibility of reverting a cell's PD-state to normality by appropriate epigenetic reprogramming. In here, we propose an in vitro relatively high throughput search for a cocktail of molecules that induces an epigenetic reversal of the PD-state. A generic multi-tissue PD-state phenotype appears to be a defect on mitochondrial bioenergetics. In the above search, we suggest utilizing a metabolic challenge as a preliminary screen for assessing, via improvement of energy metabolism, reversal of the PD-state.
authors.affiliation: Systems Biology Group, Biocant - Biotechnology Innovation Center, Cantanhede, Portugal. andre.valente@biocant.pt
authors.forename: André X C N
authors.initials: AX
authors.lastname: Valente
authors.forename: Ricardo Pires
authors.initials: RP
authors.lastname: das Neves
authors.forename: Paulo J
authors.initials: PJ
authors.lastname: Oliveira
mesh_terms: D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000235:genetics* / Q000628:therapy
chemical_list: D035683:MicroRNAs