Epigenetic engineering to reverse the Parkinson's expression state

Parkinsonism & Related Disorders
André X C N ValentePaulo J Oliveira

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.

References

Dec 1, 1989·Annals of Neurology·W D ParkerJ K Parks
Jan 1, 1994·Journal of Neural Transmission. Parkinson's Disease and Dementia Section·C MytilineouM D Yahr
Oct 1, 1996·Annals of Neurology·R H SwerdlowW D Parker
Jul 17, 1998·Journal of the Neurological Sciences·M GuA H Schapira
Nov 14, 2002·Neurotoxicology·Donato A Di MonteAmy B Manning-Bog
Feb 6, 2004·Journal of Neurochemistry·Patricia A TrimmerW Davis Parker
May 14, 2004·Journal of the Neurological Sciences·Kirstin Winkler-StuckWolfram S Kunz
Feb 3, 2005·Nature Reviews. Drug Discovery·Curtis T KeithBrent R Stockwell
May 18, 2005·Neuroscience Letters·Andrew W MichellRoger A Barker
Oct 1, 1988·Plant Physiology·P Cooper, D R Ort
Sep 9, 2006·Human Molecular Genetics·Eirene KontopoulosMel B Feany
Nov 15, 2006·Methods : a Companion to Methods in Enzymology·Dana J HuebertBradley E Bernstein
Mar 7, 2007·British Journal of Pharmacology·P S Whitton
Mar 16, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Lisa D MarroquinYvonne Will
Oct 27, 2007·Neuropathology and Applied Neurobiology·C H HawkesH Braak
Jul 2, 2008·Parkinsonism & Related Disorders·A H Schapira
Aug 20, 2008·Journal of Biology·Zoltan SpiroPeter Csermely
Nov 4, 2008·Nature Clinical Practice. Neurology·Claire Henchcliffe, M Flint Beal
Mar 31, 2009·Experimental Neurology·Patricia A Trimmer, James P Bennett
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·C Warren Olanow, Stanley B Prusiner
Sep 16, 2009·Current Pharmaceutical Design·Tiago Fleming Outeiro, Joaquim Ferreira
Feb 4, 2010·Nature Reviews. Genetics·Peter W Laird
Apr 7, 2010·Science Translational Medicine·Anders BjörklundDeniz Kirik
May 7, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ahmad JowaedUllrich Wüllner
Aug 28, 2010·Proceedings of the National Academy of Sciences of the United States of America·Gunnar HargusOle Isacson
Oct 13, 2010·Journal of Geriatric Psychiatry and Neurology·Lynn M BekrisCyrus P Zabetian
Oct 21, 2010·BMC Neurology·Pilar del HoyoFélix Javier Jiménez-Jiménez
Feb 8, 2011·Journal of Biotechnology·Regina MargisCarlos R M Rieder
Feb 8, 2011·The Journal of Biological Chemistry·Paula DesplatsEliezer Masliah
Feb 16, 2011·Proceedings of the National Academy of Sciences of the United States of America·Lisa S ShockShirley M Taylor
Apr 9, 2011·Cell Stem Cell·Frederick Anokye-DansoEdward E Morrisey
Apr 22, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Philip SeiblerDimitri Krainc

❮ Previous
Next ❯

Related Concepts

Related Feeds

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.

Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.

ATP Synthases

ATP synthases are enzymes located in the inner mitochondrial membrane that catalyze the synthesis of ATP during cellular respiration. Discover the latest research on ATP synthases here.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

© 2021 Meta ULC. All rights reserved