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

Abstract

Neurogenesis is a key mechanism of brain development and plasticity, which is impaired in chronic neurodegeneration, including Parkinson’s disease. The accumulation of aberrant α-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 α-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.

Hypoxia and Alpha-Synuclein: Inextricable Link Underlying the Pathologic Progression of Parkinson's Disease

“…α-syn has powerful physiological functions: maintaining synaptic function (Longhena et al, 2019 ), influencing neurotransmitters such as dopamine release (Abeliovich et al, 2000 ; Salmina et al, 2021 ), maintaining cell membrane homeostasis (Fusco et al, 2018 ), influencing microglial production and function (Booms and Coetzee, 2021 ), participating in lysosomal and mitochondrial activities (Tripathi and Chattopadhyay, 2019 ), and scavenging heavy metals (Harischandra et al, 2015 ). However, compared with its physiological function, its pathological function has attracted more attention and has been studied more widely, mainly because it plays an irreplaceable role in the pathogenesis of PD.…”

Migratory Response of Cells in Neurogenic Niches to Neuronal Death: The Onset of Harmonic Repair?

“…Pathophysiological causes of α-syn accumulation are still under discussion, but some of these determining factors have already been identified: genetic alterations, oxidative stress, neuroinflammation, mitochondrial alterations, and aberrant neurogenesis [ 117 , 118 , 119 , 120 , 121 ].…”

The Role of Cannabinoid Type 2 Receptors in Parkinson’s Disease

“…In addition, another mechanism involved in the pathogenesis of PD is excitotoxicity, that is, the pathological process through which neurons are damaged and killed following exaggerated stimulation of glutamatergic receptors by glutamate or similar substrates [ 13 ]. Moreover, neurogenesis, an important mechanism of brain development and plasticity, is impaired in PD [ 14 ].…”