Research Progress of Insulin-like Growth Factor-1 in Major Neurodegenerative Diseases

Major neurodegenerative diseases (NDDs) represent a large category of disorders characterized by the progressive loss of structure, function, or eventual death of neuronal cells in the brain and spinal cord. Current conventional therapeutic strategies for NDDs primarily focus on symptomatic relief. In contrast, IGF-1 is a pleiotropic protein with neurotrophic, synaptogenic, and anti-apoptotic properties, and its neuroprotective potential has been demonstrated in various preclinical models of Alzheimer’s disease, Parkinson’s disease, and other NDDs. However, the clinical efficacy of IGF-1-based interventions—whether for symptomatic relief or disease modification—has not been established in humans. Research on IGF-1 as a therapeutic target for NDDs remains predominantly preclinical, and its translation into effective clinical treatments requires further validation. This narrative review summarizes the mechanisms of action and therapeutic advances of IGF-1 in the progression of NDDs, encompassing the following four aspects: (1) Strategies based on signaling pathway regulation that target key pathways such as IGF-1/PI3K/Akt to reduce neuronal loss, promote synaptogenesis and structural remodeling, correct anomalous tau hyperphosphorylation, and improve amyloid-β (Aβ) clearance impairment. (2) Strategies based on restoring central sensitivity that focus on ameliorating cerebral insulin/IGF-1 resistance and utilizing agents to indirectly restore the neuroprotective function of IGF-1, thereby delaying cognitive decline. (3) Strategies based on delivery systems: in animal models, these employ viral vectors or nanomaterials to achieve targeted brain delivery of IGF-1, effectively promoting the survival of dopaminergic and motor neurons. (4) Future research directions that further elucidate the dynamic evolution of IGF-1 signaling across different disease stages and the development of stage-specific regulatory strategies. This review discusses approaches to restoring central IGF-1 signaling, ameliorating cerebral insulin resistance, and improving brain-targeted delivery, while emphasizing that their therapeutic relevance remains predominantly preclinical and requires validation in human studies.