New Developments in Professor Timothy Foley, Ph.D.’s Chemistry Research

A provocative proposal by biochemistry professor Timothy Foley, Ph.D., based on an extensive review of existing research and results from his own lab, questions a broadly-accepted theory that neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis (ALS), are caused by “oxidative stress” and, more specifically, by “free radical”-induced brain damage.

In an article published in Cellular and Molecular Neurobiology, in which he references 158 research studies, Dr. Foley puts forth a new hypothesis. Specifically, he postulates that over-activation of pathways likely designed to protect against oxidative stress may generate an overlooked “reductive stress” – the opposite of oxidative stress – especially in the extracellular spaces of synapses which mediate communication between neurons. Dr. Foley proposes that the increased reduction, or addition of electrons, to regulatory sulfur-containing groups on synaptic membrane proteins, can promote aberrant changes in synaptic activity. He has termed this view the “reductive reprogramming” hypothesis of neurodegeneration.

“The biochemical pathways or reactions that begin to derail healthy brain aging and set the course for neurodegenerative disease remain unknown and, for the last 30 years, the research has focused on reactions that are relevant to advanced stages of the disease,” said Dr. Foley. “One longstanding and dominate theory of neurodegenerative disorders has been that neuron dysfunction and degeneration results from aberrant nutrient and oxygen metabolism resulting in what is called oxidative stress.”

“Oxidation refers to the removal of electrons from form molecules, a process that can potentially damage cells and impair tissue functions,” Dr. Foley said, who theorizes that the oxidative stress may be a secondary phenomenon or a response to another reaction driving the degenerative disease and is insufficient to cause functional impairment.

According to Dr. Foley, the commonly accepted oxidative stress theories of neurodegenerative disorders are “ill-defined and focused primarily on a particular type of oxidant known as “free radicals,” which are substances containing one or more unpaired electrons. Hydrogen peroxide, the most abundant oxidant in cells, is not a free radical and can act as a physiologically-important messenger molecule. He also explained that cells have a high capacity to adapt to elevated levels of oxidants by increasing reducing, or antioxidant, activities.

“Remarkably, oxidative stress theories of neurodegenerative disorders are generally accepted by the scientific and medical communities despite the fact that antioxidant supplements, such as vitamins E and C, neither lower the incidence nor slow the progression of these disorders,” said Dr. Foley noting that one study reported the use of an “antioxidant cocktail” that actually accelerated cognitive decline.

Dr. Foley said new hypotheses of neurodegenerative disorders are needed and, in the article, puts forth his own theory based on research regarding the central role played by protein sulfur atoms as sensors of cellular oxidants and reductants in vivo, a theory that he said is supported by research completed at Scranton, as well as by studies completed elsewhere.

“The reductive reprogramming hypothesis I put forth theorizes that irregular increases in compensatory antioxidant activities in neural tissues may, in principle, promote the aberrant reduction of oxidized protein sulfur on the cell surface of neurons. Oxidized sulfur on certain neuronal cell surface proteins may prevent excessive activity in the extracellular synaptic space which connects the neurons. Reversal of this oxidation by cellular antioxidants can promote synaptic dysfunction and neural cell death by a process called “excitotoxicity” – or over activation of receptors.” said Dr. Foley. “Ironically, increases in cellular reducing activities have been cited as further support for oxidative stress theories of neurodegeneration without considering the possibility that too much reduction of oxidized protein sulfur can be a bad thing.”

The paper, titled “Reductive Reprogramming: A Not-So-Radical Hypothesis of Neurodegeneration Linking Redox Perturbations to Neuroinflammation and Excitotoxicity,” was published online March 23 by Cellular and Molecular Neurobiology.

Dr. Foley’s research, some of which includes University undergraduate and master’s students as co-authors, has been published in a number of academic journals, including Neurochemical Research, Cellular and Molecular Neurobiology and Biochemical and Biophysical Research Communications. He has served as a faculty mentor for numerous students. Several students who conducted research with him have won Goldwater Scholarships, which are the premier undergraduate scholarships for the fields of mathematics, natural sciences and engineering.

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Dr. Foley teaches CHEM 550 (Biochemical Structure and Function), 551 (Biocatalysis and Metabolism), and 555 (Chemical Toxicology) in our graduate program.

He also has seven graduate students currently working in his research group.

Learn more about the Chemistry program at The University of Scranton.

DPT Students Share Exciting Research Nationally

Thirty-Four University of Scranton Doctor of Physical Therapy (D.P.T.) students presented research at the American Physical Therapy Association’s Combined Sectors Meeting in Washington, D.C., in January and four D.P.T. students will present their research at the Novel Physiotherapies and Physical Rehabilitation Conference in London in August. The students conducted the research and made the poster presentations with seven physical therapy faculty members, who served as their advisors.

 

At the January conference, D.P.T. students Omar Amer, Scotch Plains, New Jersey; Berta Carmo, Parsippany, New Jersey; Dannylyn Manabat, Long Beach, California; and Jonathan Mayes, Dublin (PA) presented “The Effects of Blood Flow Restriction Therapy on Physical Performance in Adults as Compared to Standard Physical Exercise and Control Groups: A Systematic Review.” Their research was conducted with faculty advisor Peter Leininger, Ph.D.

D.P.T. students Megan J. Manzo ’16, Shelton, Connecticut; Colleen E. Smith ’16, Moscow; Emily M. Suchocki ’16, West Wyoming; and Gianna M. Vitolo ’16, Denville, New Jersey; and faculty advisor Dr. Leininger, presented “Effects of Combined Skilled Aquatic and Land Based Therapy Compared to Land Therapy Alone on Balance and Gait in Adults after a Stroke: A Systematic Review.”

D.P.T. students Stephanie Klug ’16, Morresville, North Carolina; Molly Loftus ’16, Mount Carmel; and Stephanie Zaccaria ’16, Oradell, New Jersey; and faculty advisors Dana Maida, D.P.T., and Janette Scardillo, D.P.T., presented their study “The Effects of Early Mobility in Reducing Length of Stay for Adult Patients in the Intensive Care Unit Due to Trauma: A Systematic Review.”

D.P.T. students Kevin Whelan ’16, Bronx, New York; William Wilcox, Exton; and Alissa Zajac ’16, Oxford, New Jersey, presented “How Is Graded Exercise Testing Being Used in the Clinical Management of Individuals Following a Concussion: A Systematic Review.” Their research was conducted with faculty advisor Dr. Scardillo.

D.P.T. students Danielle Frank ’16, Scranton; Sarah Kosik ’16, Pittston; Courtney Jo James Medfield ’16, Massachusetts; and Krista Ziegler ’16, Scranton, presented their study “The Effect of Transcranial Direct Current Stimulation on Balance and Mobility in Children with Cerebral Palsy: A Systematic Review.” Their research was conducted with faculty advisors Nicholas Rodino, D.P.T., and Renee Hakim, Ph.D.

D.P.T. students William Cavanaugh, Plains; John Huller ’16, Hicksville, New York; Nicholas Mullery ’16, Clark, New Jersey; and Joseph Pichiarello ’16, Dumnore, presented “The Impact of Home Health Care on Cost Effectiveness Compared to Other Post-Acute Settings in Individuals Status Post Total Joint Arthroplasty: A Systematic Review” Their research was conducted with faculty advisor Tracey Collins, Ph.D.

D.P.T. students Lauren Bonitz ’16, Endicott, New York; Megan Fasano ’16, Blue Bell; Meghan Goyden, Endwell, New York; and Caroline Segota ’16, Floral Park, New York, presented their study “Effectiveness of Gait Interventions in Improving Gait in Adults with Ataxia: A Systematic Review.” Their research was conducted with faculty advisor Jennifer Schwartz, D.P.T.

D.P.T. students Maria Gentile ’16, Jefferson Township; Cassandra Lucke ’16, Archbald; Shannon McSherry ’16, Carmel, New York; and Devin Ryan, Blackwood, New Jersey, presented “The Effect of Equine Related Therapy on Physical and Psychological Well-Being of Older Adults: A Systematic Review.” Their research was conducted with faculty advisors Dr. Schwartz and Dr. Maida.

D.P.T. students Levi Haldeman, Lehighton; Lisa Jackowitz ’16, Moosic; Aaron Oquendo ’16, Wanaque, New Jersey; and Matthew Wells ’16, Hillsborough, New Jersey and faculty advisor Dr. Hakim, presented “The Effects of Intramuscular FES on Objective Gait Measures in Adult Patients with Chronic Stroke: A Systematic Review.”

In addition, Dr. Hakim and University graduates Cassandra Fitzgerald ’15, D.P.T.’18, Fairfield, Connecticut; Elizabeth Palladino ’15, D.P.T.’18, Howell, New Jersey; andSean Scully ’15, D.P.T.’18, Sewell, New Jersey, presented their study “Functional Outcomes of Patients with Orthopedic Diagnoses Receiving Pro Bono Physical Therapy Services in a Student-Run Clinic: A Retrospective Study.”

Poster presentations of research studies were also made at the Washington, D.C., conference by faculty members, including Dr. Maida and Barbara Wagner, D.P.T., faculty emerita, and Heidi Bockelkamp, D.P.T., market director of rehabilitation services at Regional Hospital of Scranton, presented their studies “Determining AM-PAC  ‘6-Clicks’ Cutoff Scores based on Type of Joint Replacement to Predict Discharge Destination” and “Determining AM-PAC ‘6-Clicks’ Cutoff Scores based on Patient Age to Predict Discharge Destination Following Elective Joint Replacement.”

The American Physical Therapy Association’s more than 100,000 members include physical therapists, physical therapist assistants and students of physical therapy.

In addition, D.P.T. students Jamie Christensen, Branchville, New Jersey; Maura McGowan ’16, Scranton; Lindsay McGraw ’16, Lakewood; and Cory Piening, Horsham, will present “The Effect of Virtual Reality Training on Balance and Mobility in Adults with Moderate to Severe Traumatic Brain Injury: A Systematic Review” at the Novel Physiotherapies & Physical Rehabilitation Conference in August in London. Their research was conducted with faculty advisor Dr. Hakim.

Story originally shared in Royal News.