Neurogenesis describes the fundamental process of generating neurons that integrate into existing circuits. Although originally thought to cease after foetal and early postnatal development, neurogenesis is now known to persist in adult mammals in restricted brain regions. Neurogenesis is important in learning and memory, and impaired neurogenesis is implicated in ageing and neurodegenerative disorders such as Alzheimer’s disease (AD), a progressive and terminal dementia. Traditional pathological hallmarks of AD are abnormal amyloid precursor protein (APP) processing, amyloid (A)-β plaque deposition, and increased soluble Aβ. We discovered that TAG1, an F3/contactin family member, is a novel APP ligand that mediates foetal neurogenesis (Ma et al., Nature Cell Biology, 2008; CIA)1,2. TAG1 increases APP intracellular domain (AICD) release and activation in a γ-secretase-dependent manner1. We recently proved that AICD negatively modulates neuronal differentiation through miR-663 (Shu et al., Cell Death and Disease, 2015. CIA)3 and miR-574-5p4. In foetal neural stem cells (NSCs), the TAG1-APP interaction negatively regulates neurogenesis (Fig. 1), and there are supporting data that TAG1-APP signalling participates in neural development and pathological APP dysregulation29,30. Together, these findings demonstrate a critical role for TAG1-APP signalling in brain development. Supported by extensive preliminary data, we hypothesise that downregulation of adult neurogenesis participates in AD pathogenesis through the TAG1-APP signalling pathway.
anatomy, neuroscience, stem cells, micro RNA, Department of Anatomy & Developmental Biology
Biomedicine Discovery Institute (School of Biomedical Sciences) » Anatomy and Developmental Biology
Masters by research
Top-up scholarship funding available