Adult Neurogenesis in Neurodegenerative Diseases: Figure 1.

Abstract

Adult neurogenesis is limited to specific brain regions in the mammalian brain, such as the hippocampal dentate gyrus and the subventricular zone/olfactory bulb system.Alterations in adult neurogenesis appear to be a common hallmark in different neurodegenerative diseases including Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD).This is remarkable, because the distinct pathological proteins responsible for the different diseases induce the loss of different neural populations.Impaired adult neurogenesis was shown in numerous animal models of neurodegenerative diseases; however, only few postmortem studies have been performed.We will review concepts related to the interplay between cellular plasticity in regions of adult neurogenesis with a specific focus on cellautonomous and non-cell-autonomous factors.Furthermore, various strategies aimed to stimulate neuronal plasticity will be discussed within the context of a potential translation into therapeutic approaches for neuropsychiatric symptoms associated with PD, HD, and AD. REGULATION OF NEUROGENESIS IN THE ADULT BRAINA ltman and colleagues were the first scientists to report adult neurogenesis (Altman and Das 1965; Altman 1969), and this observation changed the dogma that the mammalian brain is incapable of generating new neurons.New neurons generated throughout life are one component of brain plasticity-a cellular processhowever, limited to distinct brain regions harboring adult neural stem and precursor cells, primarily the subventricular zone (SVZ) adjacent to the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus.As described in detail elsewhere in the literature, adult neurogenesis involves several crucial steps of neural development.An important aspect regarding adult neurogenesis is its modulation as a result of a variety of genetic, epigenetic, and transcriptional factors as well as environmental factors, age, and acute and chronic diseases (Ma et al. 2010;Mu et al. 2010).At this point, one may ask: Why is the generation of new neurons in distinct regions of the brain important for neurodegenerative diseases?Gradual loss of different neuronal populations occurs in monogenic and sporadic neurodegenerative diseases.Diseased neurons have