Broad-spectrum antioxidant and neuroprotective Prussian blue nanocatalyst for therapeutic intervention in autism spectrum disorder.

in Redox biology by Yan Gong, Lele Yu, Lili Xia, Jilu Jin, Yue Lang, Shini Feng, Wei Feng, Fuxue Chen, Yu Chen

TLDR

  • PB NPs show promise as a novel therapeutic approach for ASD, effectively scavenging ROS, attenuating apoptosis, and mitigating neuroinflammation, leading to improved social interaction, reduced anxiety, and enhanced cognitive functions.

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by diverse clinical presentations, often associated with dysregulated oxidative stress mechanisms leading to heightened production of reactive oxygen species (ROS) in the brain. Due to its multifactorial etiology, effective therapeutic approaches for ASD remain challenging to ascertain. This work engineers Prussian blue nanoparticles (PB NPs) designed to mimic the enzymatic functions of key antioxidants such as superoxide dismutase, glutathione peroxidase, catalase, and peroxidase. PB NPs effectively scavenge ROS and restore cellular redox homeostasis. These nanoparticles attenuate neuronal apoptosis by reducing activation of apoptotic markers like cleaved caspase-3 and B-cell lymphoma-2 associated X protein, while enhancing the expression of anti-apoptotic protein B-cell lymphoma-2. Furthermore, PB NPs mitigate neuroinflammation by downregulating pro-inflammatory cytokines and upregulating anti-inflammatory cytokines, thereby alleviating glial cell hyperactivity. In preclinical ASD models, PB NPs significantly improve social interaction deficits, diminish anxiety-like behaviors, and enhance cognitive functions. The therapeutic application of PB NPs represents a notable advancement in ASD treatment, offering a novel approach for clinical intervention aimed at enhancing the quality of life for individuals affected by ASD.

Overview

  • The study aims to develop Prussian blue nanoparticles (PB NPs) as a therapeutic approach for autism spectrum disorder (ASD).
  • PB NPs are designed to mimic the enzymatic functions of antioxidants and scavenge reactive oxygen species (ROS) to restore cellular redox homeostasis.
  • The primary objective is to assess the efficacy of PB NPs in preclinical ASD models, focusing on social interaction deficits, anxiety-like behaviors, and cognitive functions.

Comparative Analysis & Findings

  • PB NPs effectively scavenge ROS, reducing activation of apoptotic markers and enhancing the expression of anti-apoptotic proteins.
  • PB NPs attenuate neuronal apoptosis and mitigate neuroinflammation by downregulating pro-inflammatory cytokines and upregulating anti-inflammatory cytokines.
  • In preclinical ASD models, PB NPs significantly improve social interaction deficits, diminish anxiety-like behaviors, and enhance cognitive functions.

Implications and Future Directions

  • The study's findings suggest that PB NPs may represent a novel therapeutic approach for ASD, offering a potential avenue for enhancing the quality of life for individuals affected by the disorder.
  • Future studies should investigate the long-term effects of PB NPs and their potential use in combination with other therapies for ASD.
  • The potential of PB NPs as a therapeutic agent for ASD highlights the importance of exploring innovative, multi-faceted approaches for this complex neurodevelopmental disorder.
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