ORCID Profile
0000-0002-2327-9791
Current Organisations
Haley Titus Strategy LLC
,
Northwestern University Feinberg School of Medicine
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Wiley
Date: 10-09-2019
DOI: 10.1111/JNC.14829
Abstract: The past 20 years have resulted in unprecedented progress in understanding brain energy metabolism and its role in health and disease. In this review, which was initiated at the 14th International Society for Neurochemistry Advanced School, we address the basic concepts of brain energy metabolism and approach the question of why the brain has high energy expenditure. Our review illustrates that the vertebrate brain has a high need for energy because of the high number of neurons and the need to maintain a delicate interplay between energy metabolism, neurotransmission, and plasticity. Disturbances to the energetic balance, to mitochondria quality control or to glia-neuron metabolic interaction may lead to brain circuit malfunction or even severe disorders of the CNS. We cover neuronal energy consumption in neural transmission and basic ('housekeeping') cellular processes. Additionally, we describe the most common (glucose) and alternative sources of energy namely glutamate, lactate, ketone bodies, and medium chain fatty acids. We discuss the multifaceted role of non-neuronal cells in the transport of energy substrates from circulation (pericytes and astrocytes) and in the supply (astrocytes and microglia) and usage of different energy fuels. Finally, we address pathological consequences of disrupted energy homeostasis in the CNS.
Publisher: Wiley
Date: 09-07-2022
DOI: 10.1002/GLIA.24231
Abstract: Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune disease characterized by inflammation, demyelination, and neurodegeneration. The ideal MS therapy would both specifically inhibit the underlying autoimmune response and promote repair/regeneration of myelin as well as maintenance of axonal integrity. Currently approved MS therapies consist of non‐specific immunosuppressive molecules/antibodies which block activation or CNS homing of autoreactive T cells, but there are no approved therapies for stimulation of remyelination nor maintenance of axonal integrity. In an effort to repurpose an FDA‐approved medication for myelin repair, we chose to examine the effectiveness of digoxin, a cardiac glycoside (Na + /K + ATPase inhibitor), originally identified as pro‐myelinating in an in vitro screen. We found that digoxin regulated multiple genes in oligodendrocyte progenitor cells (OPCs) essential for oligodendrocyte (OL) differentiation in vitro, promoted OL differentiation both in vitro and in vivo in female naïve C57BL/6J (B6) mice, and stimulated recovery of myelinated axons in B6 mice following demyelination in the corpus callosum induced by cuprizone and spinal cord demyelination induced by lysophosphatidylcholine (LPC), respectively. More relevant to treatment of MS, we show that digoxin treatment of mice with established MOG 35‐55 ‐induced Th1/Th17‐mediated chronic EAE combined with tolerance induced by the i.v. infusion of biodegradable poly(lactide‐co‐glycolide) nanoparticles coupled with MOG 35‐55 (PLG‐MOG 35‐55 ) completely ameliorated clinical disease symptoms and stimulated recovery of OL lineage cell numbers. These findings provide critical pre‐clinical evidence supporting future clinical trials of myelin‐specific tolerance with myelin repair/regeneration drugs, such as digoxin, in MS patients.
Location: United States of America
Location: United States of America
Location: United States of America
Location: United States of America
No related grants have been discovered for Haley Titus.