Novel Approaches Used to Examine and Control Neurogenesis in Parkinson′s Disease

Neurogenesis is a key mechanism of brain development and plasticity, which is impaired in chronic neurodegeneration, including Parkinson's disease. The accumulation of aberrant alpha-synuclein is one of the features of PD. Being secreted, this protein produces a prominent neurotoxic effect, alters synaptic plasticity, deregulates intercellular communication, and supports the development of neuroinflammation, thereby providing propagation of pathological events leading to the establishment of a PD-specific phenotype. Multidirectional and ambiguous effects of alpha-synuclein on adult neurogenesis suggest that impaired neurogenesis should be considered as a target for the prevention of cell loss and restoration of neurological functions. Thus, stimulation of endogenous neurogenesis or cell-replacement therapy with stem cell-derived differentiated neurons raises new hopes for the development of effective and safe technologies for treating PD neurodegeneration. Given the rapid development of optogenetics, it is not surprising that this method has already been repeatedly tested in manipulating neurogenesis in vivo and in vitro via targeting stem or progenitor cells. However, niche astrocytes could also serve as promising candidates for controlling neuronal differentiation and improving the functional integration of newly formed neurons within the brain tissue. In this review, we mainly focus on current approaches to assess neurogenesis and prospects in the application of optogenetic protocols to restore the neurogenesis in Parkinson's disease.

Automated summary

Neurogenesis is crucial for brain development and plasticity, but it is impaired in chronic neurodegenerative diseases like Parkinson's disease. The accumulation of aberrant alpha-synuclein in PD leads to neurotoxic effects and impaired synaptic plasticity, affecting neurogenesis. The development of optogenetics offers new hopes for treating PD neurodegeneration by targeting neurogenesis.