Neurological disorders affect more than 1 in 3 people, making them a leading cause of illness and disability worldwide. Currently, there are no effective regenerative therapies, capable of halting progression or reversing neurological diseases. The presence of resident neural stem cells in the adult human central nervous system (brain and spinal cord) has inspired the development of new therapeutic approaches for brain regeneration not only to treat neurological disorders but also to promote healthy ageing. However, before we can engage adult neural stem cells for brain regeneration, we need to understand how neural stem cells are regulated.
Regeneration of neurons (main signalling cell types) and glia (non-neuronal cells) is required for basic adult brain function maintenance, including key processes such as motor skill learning and memory formation. Replacement of these cells is performed by adult neural stem cells that are located in two distinct niches in the mammalian brain: the subgranular zone in the hippocampus and the subventricular zone (SVZ) lining the lateral ventricles. The latter represents the largest pool of adult neural stem cells and is the focus of this application. SVZ neural stem cells react to changes in the local environment (niche), become activated, migrate and differentiate (transform) into neurons or glia.
The objective of this application is to define environmental signals that regulate adult SVZ neural stem cells in the homeostatic adult brain. Specifically, we will study how molecules secreted by neighbouring neurons (“neurochemicals”), including transthyretin (TTR), regulate neural stem cells. The results of this project will establish the safety and efficacy profile of TTR in the adult brain regeneration. Moreover, our results will fast-track the development of new drugs that mimic pro-regenerative properties of neurochemical TTR to treat neurological disorders.
