A novel neuroprotective mechanism in Alzheimer's disease
Alzheimer’s disease is characterised by loss of memory because of dying brain cells and brain atrophy. In addition, proteins deposit in the brain tissue forming amyloid plaques. The amyloid plaques contain short protein fragments that are toxic to brain cells, causing them to die, a process called ‘amyloid toxicity’. Recent discoveries have shown that the toxic signal of amyloid is caused by changes of brain cell molecules (i.e. components that make up the cell). However, it remains completely unknown whether there are also molecules that can inhibit or even block these toxic signals. During his fellowship, Dr Ittner will assess a novel molecule, which may protect brain cells from amyloid toxic signals. Dr Ittner aims at finding out how exactly this molecule protects brain cells from amyloid toxic signals. His project will close a gap in knowledge of protective components in brain cells and will provide part of the understanding needed to design new ways for treating Alzheimer’s disease.
Alzheimer’s disease is characterised by amyloid beta-containing plaques and tau-containing neurofibrillary tangles in the brains of patients. Amyloid beta initiates a toxic signaling cascade, called amyloid cascade, which eventually leads to brain cell death. Work from Dr Ittner’s laboratory described how the neuron-specific protein tau critically contributes to this toxic cascade and promotes signals that lead to neuronal death. This ground-breaking work has been recognised as a central mechanism in the development of Alzheimer's disease. However, how tau-mediated amyloid beta toxicity is regulated, and more importantly limited, remains completely unknown. In his fellowship, Dr Ittner will study a novel factor with limiting function in amyloid beta toxicity. Using mouse models of Alzheimer's disease, he will study a novel protective mechanism from Aβ-induced impairments in cognition and survival. He will elucidate the details of this molecular mechanism that protects brain cells from amyloid beta-induced toxicity. This project will close a gap in knowledge of regulating mechanisms in the toxic amyloid cascade and will provide new ways of molecular therapy of amyloid toxicity underlying Alzheimer's disease.
Dr Ittner is a Post-doctoral Research Associate based at the Dementia Research Unit, School of Medical Sciences, University of New South Wales. He began his two year half funded AADRF fellowship in early 2015.