Investigator, Assoc Prof (M) Psychiatry, Mass General Research Institute

Associate Professor of Psychiatry (Neuroscience) Harvard Medical School

5' untranslated regions; alzheimer's disease; amyloid beta-protein precursor; amyloid precursor protein; brain iron homeostasis; cytokin dysregulation; ferritins; iron; iron response element; neurochemistry; neuropsychiatric disorders; neurotoxicity; parkinson's disease; protein biosynthesis

Neurochemistry is the study of fundamental genetic mechanisms in the human body that regulate how chemicals govern the activity of nerve cells. The failure of these mechanisms can lead to the onset of devastating life-threatening and chronic diseases, foremost among them: Alzheimer’s disease, Parkinson’s disease, amyotrophic laterals sclerosis (ALS), autism, schizophrenia and major depression.

A second critical area of neurochemistry research is how cell signaling through molecules called cytokines regulate processes in the brain and in other organs. Cytokine dysregulation has been implicated in many diseases of the developing intestine and brain during gestation.

Over the past decade and more, Jack Rogers, PhD, has been a leader in conducting research that has transformed the way seemingly separate neurodegenerative diseases are now viewed, revealing underlying common mechanisms at the genetic level. In doing so, Dr. Rogers and colleagues were the first scientists to identify a common therapeutic target—the iron response element—on several of the genes that code for proteins implicated in neurodegeneration. These findings may successfully target the gene that encodes the amyloid precursor protein (APP) implicated in Alzheimer’s disease, and the gene that encodes the protein alpha synuclein in Parkinson’s disease.

To advance these findings, Dr. Rogers is moving forward from these basic mechanisms to the study of molecules that can reach the iron response element—the common therapeutic target—and act to inhibit the production of the disease-causing proteins. This research is now in the in vivo testing stage using mouse models of the diseases.

Positive results in these tests will enable progression to clinical trials and, hopefully, to the development of drugs with impact across the neurodegenerative disease spectrum. The idea is to develop blockers of the genes that produce the “culprit” proteins at the pass before they can cause nerve damage. Other possible clinical benefits of this research relate to the potential of dietary interventions to protect against this neuro-degeneration.