Insulin-Like Growth Factor Dynamics in Cognitive Health
Summary
Insulin-like growth factors constitute a pivotal component of the somatotropic axis, orchestrating neurodevelopment, synaptic plasticity and maintenance of cerebral integrity across the lifespan. IGF-1 and IGF-2, polypeptide hormones resembling insulin, traverse the blood–brain barrier to engage IGF-1 receptors on neurons, glia and endothelial cells, activating the PI3K/Akt and MAPK/ERK cascades. These signals promote neuronal survival, dendritic arborisation and myelination, while modulating neuroinflammatory responses through effects on microglial and astrocytic phenotypes. Dynamic regulation of circulating and locally produced IGFs underlies age-related cognitive trajectories: optimal concentrations support memory consolidation and learning, whereas deviations above or below physiological thresholds have been linked to accelerated cognitive decline and elevated cerebrovascular risk. Binding proteins (IGFBPs) fine-tune IGF bioavailability and may exert IGF-independent neurotrophic actions. Emerging evidence implicates IGF-mediated pathways in blood–brain barrier integrity, metabolic homeostasis and repair following injury. A nuanced understanding of IGF dynamics thus holds promise for biomarker development and targeted interventions in neurodegenerative and neuropsychiatric disorders, with potential to inform stratified approaches to preserve cognitive health globally.
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Insulin-Like Growth Factor Dynamics in Cognitive Health publication trend
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Technical terms
Insulin-like growth factor-1 (IGF-1): A neurotrophic hormone that promotes neuronal growth, survival and metabolism, acting downstream of growth hormone.
Insulin-like growth factor receptor (IGF-1R): A receptor tyrosine kinase that mediates IGF-1 signalling via PI3K/Akt and MAPK/ERK pathways.
Insulin-like growth factor binding protein-2 (IGFBP-2): A carrier protein that regulates IGF-1 bioavailability and exerts independent effects on neuronal plasticity.
Neuroinflammation: Activation of microglia and astrocytes in response to injury or pathology, influencing neuronal survival and repair mechanisms.
Somatotropic axis: The endocrine network comprising growth hormone, IGFs and their binding proteins, coordinating growth and metabolic processes.
References
- Circulating insulin-like growth factor-1 and brain health: Evidence from 369,711 participants in the UK Biobank. Alzheimer's Research & Therapy (2023).
- Insulin-like growth factor-1 receptor controls the function of CNS-resident macrophages and their contribution to neuroinflammation. Acta Neuropathologica Communications (2023).
- Insulin-Like Growth Factor-1 and Neuroinflammation. Frontiers in Aging Neuroscience (2017).
- Insulin-Like Growth Factor 1: At the Crossroads of Brain Development and Aging. Frontiers in Cellular Neuroscience (2017).
- Neurotrophic and Neuroregenerative Effects of GH/IGF1. International Journal of Molecular Sciences (2017).
- IGFBP-2 Signaling in the Brain: From Brain Development to Higher Order Brain Functions. Frontiers in Endocrinology (2019).
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