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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.)

Life and societies would change significantly if memory capacity or persistence in health and disease could be enhanced. It has been known for many years that memory can be improved and strengthened. Substances known to enhance memory include hormones, neurotransmitters, neuropeptides and metabolic substrates. Recently, attention has been given to identifying the molecular mechanisms and targets whereby memory enhancement can be achieved. One approach would be to target the physiological changes that are induced by learning and naturally required for memory strengthening via consolidation and reconsolidation. Here, we review approaches that boost memories by targeting the cAMP response element binding protein-CCAAT enhancer binding protein (CREB-C/EBP) pathway and/or its recently identified target gene insulin-like growth factor 2 (IGF2)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Consolidation of new memories depends on a crucial phase of protein synthesis. It is widely held that, once consolidated, memories are stable and resilient to disruption. However, established memories become labile when recalled and require another phase of protein synthesis to be maintained. Therefore, it has been proposed that when a memory is reactivated it must undergo additional consolidation (reconsolidation) to persist. To determine whether reconsolidation recapitulates consolidation, in the past few years several groups have investigated whether the same molecules and pathways mediate the formation of a memory and its maintenance after reactivation. At first glance, the results appear conflicting: although both processes appear to engage the same molecules and mechanisms, brain areas involved in consolidation after initial training are not required for reconsolidation. In addition, the formation of a memory and its maintenance after reactivation seem to have distinctive temporal molecular requirements. This review concludes with a working model that could explain the apparent controversy of memory vulnerability after reactivation.