Targeting impaired adult hippocampal neurogenesis in ageing by leveraging intrinsic mechanisms regulating Neural Stem Cell activity

Ageing Res Rev. 2021 Aug 14:101447. doi: 10.1016/j.arr.2021.101447. Online ahead of print.ABSTRACTDeficits in adult neurogenesis may contribute to the aetiology of many neurodevelopmental, psychiatric and neurodegenerative diseases. Genetic ablation of neurogenesis provides proof of concept that adult neurogenesis is required to sustain complex and dynamic cognitive functions, such as learning and memory, mostly by providing a high degree of plasticity to neuronal circuits. In addition, adult neurogenesis is reactive to external stimuli and the environment making it particularly susceptible to impairment and consequently contributing to comorbidity. In the human brain, the dentate gyrus of the hippocampus is the main active source of neural stem cells that generate granule neurons throughout life. The regulation and preservation of the pool of neural stem cells is central to ensure continuous and healthy adult hippocampal neurogenesis (AHN). Recent advances in genetic and metabolic profiling alongside development of more predictive animal models have contributed to the development of new concepts and the emergence of molecular mechanisms that could pave the way to the implementation of new therapeutic strategies to treat neurological diseases. In this review, we discuss emerging molecular mechanisms underlying AHN that could be embraced in drug discovery to generate novel concepts and targets to treat diseases of ageing including neurodegeneration. To support this, we review ...
Source: Ageing Research Reviews - Category: Genetics & Stem Cells Authors: Source Type: research