Brain Disorders & Therapy

Novel strategies for stroke therapy based on targeting of mitochondrial dysfunction and ER stress signaling pathways

Global Summit on Stroke

August 03-05, 2015 Birmingham, UK

Howard Prentice

Scientific Tracks Abstracts: Brain Disord Ther

Abstract:

Available stroke treatments are largely ineffective and the time window for efficacy for TPA is limited to a few hours. To
investigate new treatments for stroke we have compared administration of the amino acid taurine with a novel multidrug
combination in rodent models targeting both mitochondrial pathways and endoplasmic reticulum (ER) stress signaling
pathways. Taurine has been shown to prevent calcium overload in neural cells by blocking transport through calcium channels
including the L-, P/Q- and N-type calcium channels and the NMDA receptor channel. In a transient focal ischemia stroke
model taurine elicits protection by inhibiting both the IRE-1 and ATF-6 ER stress pathways. Our multi-drug treatment
involves three components: 1. Granulocyte-colony stimulating factor (G-CSF) which elicits neuroprotection via inhibition
of ER stress pathways and by inducing stem cell mobilization 2. DETC-MeSO, which acts as a partial NMDA antagonist and
prevents apoptosis by inhibiting the PERK pathway but not the ATF-6 pathway and 3.Sulindac which has been reported to act
as a pre-conditioning agent and in the stroke model elicits induction of pro-survival proteins including Hsp27 and Akt as well
as inhibiting the ER stress pathway component ATF-6. While each of the components of the multidrug treatment individually
can elicit protection, lower doses used in combination shoe promise for eliciting synergistic pro-survival responses through
targeting of key downstream stress responses. The interventions tested augment expression of pro-survival moleculesat the
same time as inhibiting important pro-death responses including mitochondrial dysfunction, calcium overload and apoptosis
elicited through ER stress signaling.

Biography :

Howard Prentice obtained his Ph.D. from the University of London, UK and after post-doctoral training in the USA he held faculty position at the University of Glasgow, UK
from 1993-2000. He then joined Florida Atlantic University in Boca Raton where he is currently Associate Professor of Biomedical Sciences in the College of Medicine.
From 2013-2014 he was visiting Associate Professor at Harvard Medical School, Boston. He has more than 60 peer reviewed publications. He has been serving on study
sections for the American Heart Association and the NIH and on editorial boards of several international scientific journals.