Adult neurogenesis and neurodegenerative disease

Abstract

Advances in stem cell biology of the adult brain and the discovery of adult neurogenesis have raised the hope that neurodegenerative disorders might ultimately become amenable to causal therapy. Stem cells contribute to cellular plasticity during the lifespan, and in some sense, brain development never ends. However, neurodegeneration is not just a lack of neuroregeneration, and cell genesis in the adult brain does not apparently lead to successful endogenous responses to neurodegeneration. The brain heals poorly; nevertheless, the onset, severity and progression of neurodegenerative disorders show large variation and can often be influenced by cognitive training and physical activity. Rather than providing endogenous repair, cellular plasticity, including adult neurogenesis might thus contribute to the 'cognitive reserve' that determines how well an organism can compensate for neurodegeneration. From this perspective, neurodegenerative disorders, such as Alzheimer's, Parkinson's, Lewy body and Huntington's diseases, might share a relevant biological principle that even links them to psychiatric disorders, like depression, which are not considered 'neurodegenerative' in a classical sense. However, the integration of neuroregenerative phenomena and most notably adult neurogenesis into the concepts of neurodegeneration is not without problems and remains speculative at present. Adult neurogenesis might be part of the physiological regenerative response and might thereby alter or alleviate symptoms, but it might also become impaired by the disease mechanism and thereby contribute to the symptoms of neurodegeneration. In any case, the extent to which effects on the level of cellular plasticity, be it degenerative or regenerative, are relevant functionally remains to be determined. The present review gives an overview of what is known about cell genesis and adult neurogenesis in neurodegenerative disorders and discusses how cellular plasticity might be part of concepts that integrate aspects of development and cellular plasticity into neurodegeneration.