Neurogenesis in Neurodegeneration: Multifactorial Regulation, Mechanisms of Impairment, and Therapeutic Strategies
摘要
Objectives. To systematize current data on neurogenesis and its involvement in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, with an emphasis on the molecular mechanisms of regulation, the nature of impairments during neurodegeneration, and evaluation of therapeutic approaches aimed at stimulating neurogenesis. Materials and methods. Articles published in the scientific databases Scopus, PubMed, and Google Scholar over the past five years were assessed. Particular attention was paid to studies addressing neurogenesis and its role in the pathogenesis of neurodegenerative diseases. The review included studies that met the following criteria: publications from the past five years reflecting current data on neurogenesis, clearly defined experimental and clinical methods, published in peer-reviewed international journals with a high impact factor, reliable statistical data supporting the results. Studies with limited sample sizes and insufficient statistical power, lacking a transparent methodology, or having low levels of reproducibility, reviews without a clear focus on neurogenesis or its relationship with neurodegenerative diseases, and studies with insufficient information on the technical and analytic methods used were excluded. Results. Current research has significantly expanded our understanding of neurogenesis and its role in neurodegenerative diseases. Neurogenesis has been confirmed to occur in specific areas of the adult brain, including the hippocampus, where it is involved in cognitive processes such as learning, memory consolidation, spatial adaptation, cognitive flexibility, and the regulation of affective behavior. However, the extent and functional significance of neurogenesis in different areas of the brain remain under discussion. Neurodegenerative diseases have different impacts on neurogenesis: in Alzheimer’s disease, studies in animal models have demonstrated impaired neurogenesis, though data from humans are contradictory: decreased neurogenesis has been seen in the early stages of the disease, though increases are sometimes recorded, perhaps as a compensatory mechanism. Factors influencing neurogenesis in Alzheimer’s disease include the accumulation of β-amyloid and tau protein, neuroinflammation, mitochondrial dysfunction, and oxidative stress. In Parkinson’s disease, neurogenesis is reduced in the subventricular zone and hippocampus as a result of degeneration of dopaminergic neurons and accumulation of α-synuclein. However, deep brain stimulation can enhance neuronal cell proliferation. Therapeutic strategies include pharmacological approaches aimed at stimulating neurogenesis, such as the use of neurotrophic factors, acetylcholinesterase inhibitors, selective serotonin reuptake inhibitors, Wnt and EGFR signaling modulators, uric acid, and MFG-E8, as well as nonpharmacological methods, including physical activity, an enriched environment, cognitive training, electrical stimulation, and music therapy. Conclusions. Neurodegenerative diseases represent a significant challenge to modern healthcare, requiring in-depth studies of the mechanisms of neurogenesis and its role in pathogenesis. Despite conflicting data on neurogenesis in adults, studies in animal models and cell technologies have demonstrated the potential for its therapeutic stimulation. Pharmacological and non-pharmacological methods, including the use of neurotrophic factors, electrical stimulation, and cognitive training, as well as cell and gene therapy, form the basis of new intervention strategies. However, issues related to controlling the differentiation and integration of new neurons remain unresolved, as do ethical aspects associated with the use of stem cells. Further interdisciplinary research seeking to elucidate the regulatory mechanisms of neurogenesis and its therapeutic potential may lead to the development of effective treatment strategies capable of slowing or even reversing the progression of neurodegenerative diseases. This underscores the need to integrate cutting-edge technologies and approaches in modern neurobiology and clinical practice.