Inflammation and Autophagy: A Convergent Point between Autism Spectrum Disorder (ASD)-Related Genetic and Environmental Factors: Focus on Aluminum Adjuvants.
Loïc AngrandJean-Daniel MassonAlberto Rubio-CasillasMarika Nosten-BertrandGuillemette CrépeauxPublished in: Toxics (2022)
Autism spectrum disorder (ASD), schizophrenia, and bipolar disorder are genetically complex and heterogeneous neurodevelopmental disorders (NDDs) resulting from genetic factors and gene-environment (GxE) interactions for which onset occurs in early brain development. Recent progress highlights the link between ASD and (i) immunogenetics, neurodevelopment, and inflammation, and (ii) impairments of autophagy, a crucial neurodevelopmental process involved in synaptic pruning. Among various environmental factors causing risk for ASD, aluminum (Al)-containing vaccines injected during critical periods have received special attention and triggered relevant scientific questions. The aim of this review is to discuss the current knowledge on the role of early inflammation, immune and autophagy dysfunction in ASD as well as preclinical studies which question Al adjuvant impacts on brain and immune maturation. We highlight the most recent breakthroughs and the lack of epidemiological, pharmacokinetic and pharmacodynamic data constituting a "scientific gap". We propose additional research, such as genetic studies that could contribute to identify populations at genetic risk, improving diagnosis, and potentially the development of new therapeutic tools.
Keyphrases
- autism spectrum disorder
- oxidative stress
- bipolar disorder
- attention deficit hyperactivity disorder
- intellectual disability
- genome wide
- copy number
- cell death
- endoplasmic reticulum stress
- signaling pathway
- major depressive disorder
- healthcare
- early stage
- white matter
- resting state
- multiple sclerosis
- gene expression
- big data
- case control
- cerebral ischemia
- machine learning
- cell therapy
- mesenchymal stem cells
- prefrontal cortex
- subarachnoid hemorrhage