Role of Insulin-Like Growth Factor-1/2 and Related Signaling in Parkinson’s Disease

Parkinson’s disease (PD) is a chronically progressive neurodegenerative disorder primarily characterized by the degeneration of dopaminergic neurons within the substantia nigra pars compacta (SNpc). Insulin-like growth factor 1 (IGF-1) which is a protein recognized for its neuroprotective properties is naturally declines with aging. This age-related reduction in IGF-1 and its associated signaling pathways has been hypothesized to contribute to PD pathogenesis. Intriguingly, the early stage of PD is often marked by elevated brain and peripheral IGF-1 levels, suggesting a compensatory response to counteract progressive PD neuropathology and slowing disease progression. Conversely, as neurodegeneration advances in later stages of PD, a notable reduction in both IGF-1 levels and its expression is observed. Despite these seemingly contradictory findings regarding IGF-1’s dynamic changes throughout the disease course, its precise role in the complex pathogenesis of PD remains largely undefined. This review aims to comprehensively explore and critically discuss the multifaceted involvement of IGF-1 signaling in PD, and to evaluate the potential therapeutic benefits of targeting this pathway for the effective management of the disease.