IGF2 in memory, neurodevelopmental disorders, and neurodegenerative diseases.

Insulin-like growth factor 2 (IGF2) emerged as a critical mechanism of synaptic plasticity and learning and memory. Deficits in IGF2 in the brain, serum, or cerebrospinal fluid (CSF) are associated with brain diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Increasing IGF2 levels enhances memory in healthy animals and reverses numerous symptoms in laboratory models of aging, neurodevelopmental disorders, and neurodegenerative diseases. These effects occur via the IGF2 receptor (IGF2R) - a receptor that is highly expressed in neurons and regulates protein trafficking, synthesis, and degradation. Here, I summarize the current knowledge regarding IGF2 expression and functions in the brain, particularly in memory, and propose a novel conceptual model for IGF2/IGF2R mechanisms of action in brain health and diseases.
Competing Interests: Declaration of interests C.M.A. is the founder and current president of Ritrova Therapeutics, Inc., a start-up that stemmed from IGF2 and IGF2R studies and aims to develop treatment for neurodevelopmental disorders and neurodegenerative diseases.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)