Pre-clinical development of novel cell-penetrating peptides to block tau-associated neurotoxicity for the treatment of dementia
Two hallmarks of Alzheimer’s disease pathology are the toxic clustering of proteins called amyloid-beta and tau, which cause the death of brain cells. A number of clinical trials of drugs that act on amyloid-beta have failed, making tau a new therapeutic alternative. Previous research has shown that a peptide, consisting of the C-terminal amino acids of N-methyl-D-aspartate receptors attached to a cell-penetrating sequence (Tat-NR2B9c), can block tau-mediated toxicity and increase brain cell survival. In this project, Dr Ariawan proposes to improve the stability of Tat-NR2B9c by incorporating it into a novel cyclic peptide scaffold. She will then examine its efficacy in an Alzheimer’s disease mouse model and determine the effects on cognition and behaviour. Furthermore, to enhance clinical translation, she will assess this peptide in brain organoids derived from people with Alzheimer’s disease. Together, these studies will generate essential pre-clinical data for a novel treatment for dementia.
Dr Daryl Ariawan is a postdoctoral research fellow in the Dementia Research Centre, Macquarie University. She works with Professor Lars Ittner on developing novel peptide therapeutics to treat Alzheimer’s disease.