Preventative measure for Chronic Traumatic Encephalopathy (CTE); Potential for small molecule iron response element targeting translation blockers of neurotoxic proteins for the treatment of Traumatic Brain Injury (TBI).

Title : Preventative measure for Chronic Traumatic Encephalopathy (CTE); Potential for small molecule iron response element targeting translation blockers of neurotoxic proteins for the treatment of Traumatic Brain Injury (TBI).

Abstract:

Repetitive traumatic brain injury (TBI)  experienced by athletes and military service personnel can lead to acquired neurodegenerative diseases.  This includes pathologies related to those of Parkinson’s disease, Alzheimer’s disease and Chronic traumatic encephalopathy (CTE), the latter being a progressive neurodegenerative disease beginning after a long period of latency following multiple TBIs. The initial symptoms of CTE consists of headache, irritability, impulsivity, aggression, depression,  short-term memory loss and heightened suicidality. These progress to include cognitive deficits and dementia.  The association of CTE with neurodegenerative disease is consistent with repetitive brain trauma and associated hyperphosphorylated tau that promotes the accumulation of other abnormally aggregated proteins including amyloid beta protein (Abeta) and alpha-synuclein. TBI is marked by increased expression of the AD associated amyloid Precursor Protein (APP),  Tau and the PD associated Alpha Synuclein (SNCA) in the brain and may also co occur with increases in prion (Prp). We noted that metal ions, particularly iron (Fe), can regulate these proteins translationally with a role in post-TBI outcomes.  Nevertheless,  little is known of the role of metals following multiple TBIs and in the development of CTE.  There are few promising drug treatments for TBI and concussion injury. Studies have shown that methylphenidate, a dopamine agonist, reduced irritability and aggression, donepezil, a cholinergic agent improved cognition, such as memory and attention. However none of these directly target  CTE associated neurotoxic proteins.  Our screened small molecules selectively target the mRNAs for APP,  SNCA, Tau and Prion 5’Untranslated regions, lowering the translation of these proteins. Our agents have the potential to be used following TBI to prevent the neurodegenerative toxic protein accumulation that lead to CTE.

Biography:

Dr. Cahill studied Biology at University College Dublin,  Ireland graduating  in 1985 with her Batchelors degree. She received her PhD degree in 1990 at the same institution. After a 3 year postdoctoral fellowship at the Babraham Research Institute,  Cambridge UK, she came to the U.S. where she carried out research at the Dana Farber Cancer Institute and several other Harvard affiliated hospitals including Massachusetts General Hospital.  She is an Assistant Professor of Psychiatry at Massachusetts General Hospital and Co-Directs the Neurochemistry lab with her colleague Dr. Jack Rogers. She has published widely in topics such as  cancer and inflammation, diabetes, neurodegenerative diseases and now alcohol use disorder,  bringing to the field her interdisciplinary background and new perspectives to this research area.