Adult neurogenesis dysfunction in Parkinson's disease: Molecular pathology and functional implications

Parkinson's disease (PD) is a neurodegenerative disorder marked by the accumulation of alpha-synuclein protein within dopamine-producing neurons and their consequent death. Although the specific etiology of PD remains unclear, emerging evidences suggest that disrupted neurogenesis plays a crucial role in pathophysiology of PD. Neurogenesis has a regenerative effect and is a promising therapeutic target for PD. Recent studies demonstrated that impaired neurogenesis in the subventricular zone (SVZ), hippocampus (HIP) and substantia nigra (SN) contributed to motor/nonmotor deficits in PD. However, the precise correlation between the pathogenesis of PD and neurogenesis remains to be explored. This study aimed to investigate the role of the dopaminergic signaling pathway, neurotrophic factors, gut microbiota, neuroinflammation, and mutations in PD-related genes in adult neurogenesis in PD. First, a comprehensive review of recent studies was carried out to explore how neurogenesis impacts PD pathophysiology. Then, the challenges and future perspectives associated with promoting endogenous neurogenesis to compensate for the loss of dopaminergic neurons in PD were investigated. The study offers promising therapeutic strategies to activate the endogenous neurogenesis in PD. Furthermore, it offers promising therapeutic strategies to activate the endogenous neurogenesis in PD. This article also emphasizes the importance of the precise manipulation of neurogenesis in PD with the aim of promoting the translation of these findings into clinical treatment.