From the Guidelines
The receptor for advanced glycation end products (RAGE) is likely to play a significant role in autism spectrum disorder (ASD) by contributing to inflammation and oxidative stress in the brain, although the provided evidence does not directly support this claim, and more research is needed to confirm this association 1. The potential involvement of RAGE in ASD is based on its role in binding to advanced glycation end products (AGEs) and other inflammatory molecules, triggering inflammatory signaling pathways and increasing oxidative stress. In the context of ASD, increased RAGE expression and activation in the brain, particularly in areas involved in social behavior and cognition, may contribute to the neuroinflammation and oxidative damage seen in ASD brains, potentially disrupting normal brain development and function, and leading to some of the behavioral and cognitive symptoms associated with ASD. Key aspects of ASD include:
- High interrater reliability and temporal stability of the diagnosis 1
- Significant decreases in social function and quality of life, even in individuals with superior cognitive abilities 1
- Co-occurring medical and mental health conditions, such as seizure disorder, gastrointestinal problems, attention-deficit/hyperactivity disorder (ADHD), anxiety, and other conditions 1 While the provided evidence does not directly address the role of RAGE in ASD, research is ongoing to better understand this connection, and potential future therapies may aim to reduce RAGE activation or block its signaling pathways. In the meantime, general anti-inflammatory approaches like dietary changes or certain supplements may help indirectly address RAGE-related inflammation, though more research is needed to confirm their efficacy in ASD, and any potential treatments would need to be part of a comprehensive approach tailored to an individual's specific needs.
From the Research
Role of RAGE in Autism Spectrum Disorder (ASD)
There is no direct evidence in the provided studies to suggest a specific role of the receptor for advanced glycation end products (RAGE) in autism spectrum disorder (ASD).
RAGE and Its Ligands
- RAGE is a promiscuous receptor that can be activated by many ligands, including damaged associated molecular patterns (DAMPs) 2
- The interaction of RAGE with its ligands induces a series of signal transduction cascades, leading to the activation of transcription factor NF-κB and increased expression of cytokines, chemokines, and adhesion molecules 3
- RAGE signaling and downstream pathways have been implicated in a wide spectrum of inflammatory-related pathologic conditions, but its role in ASD is not mentioned in the provided studies
RAGE in Immunity and Social Behavior
- RAGE is a pattern recognition receptor that plays a pivotal role in the propagation of immune responses and inflammatory reactions 4
- The ligand-RAGE interaction elicits cellular responses, including cytokine production, cell migration, phagocytosis, maturation, and polarization
- RAGE has been shown to transport oxytocin from the blood into the brain and regulate brain functions, including social behaviors, but its specific role in ASD is not discussed in the provided studies
Biological Significance and Imaging Applications of RAGE
- RAGE activation initiates a cascade of complex pathways associated with producing free radicals, cell proliferation, and immunoinflammatory processes 5
- The involvement of RAGE in the pathogenesis of disorders such as diabetes, inflammation, tumor progression, and endothelial dysfunction is well-established, but its role in ASD is not mentioned
- There is a need to develop noninvasive, molecular imaging approaches to accurately quantify RAGE levels in vivo, which could aid in the validation of RAGE and its ligands as biomarkers and therapeutic targets 5
Cellular Signalling of RAGE
- RAGE senses a variety of signalling molecules, including advanced glycation end products (AGEs), HMGB1, S100/calgranulins, β-amyloid, phosphatidylserine, C3a, and advanced oxidation protein products (AOPPs) 6
- RAGE regulates a number of cell processes, including inflammation, apoptosis, proliferation, and autophagy, but its specific role in ASD is not discussed in the provided studies