Neurogenesis, the generation of new neurons, persists in the adult mammalian brain in the subventricular zone (SVZ) / olfactory bulb system and in the hippocampus. Importantly, there is evidence that neurogenesis also takes place in humans. Newborn cells arising in the SVZ normally migrate along the rostral migratory stream to the olfactory bulb where they differentiate into GABAergic and dopaminergic neurons. Neurogenesis involves three crucial steps. Asymmetric cell division of a stem cell, resulting in one daughter stem cell and one cell which can develop into a neuron. The second step entails the migration of the newborn cell to its final and appropriate destination in the brain. The third and final step involves maturation of the cells into a neuron that forms both efferent and afferent connections within the brain. Importantly, aggregation disorders such as synucleinopathies may interfere with these different steps. It is important to note that cognitive dysfunction, depression and olfactory deficits are important pre-motor signs in Parkinson disease (PD), the most prevalent human synucelinopathy, and may be linked to an impaired hippocampal and olfactory bulb neurogenesis. Interestingly, a decreased proliferation of neural precursor cells was described in the SVZ and the hippocampus of PD patients as well as in PD animal models and specifically in mouse models of synucleinopathies. Using different transgenic synuclein models (different promoter such as PDGF and Thy1 as well as tetracycline dependent expression of synuclein) we have precisely characterized at which stage and how synuclein interferes the generation of adult newly generated cells. This knowledge may help us (1) to better understand the impact of protein aggregation in regions of cellular plasticity and (2) to develop novel strategies to maintain the capacity of the adult brain to generate new neurons.