Analyzing the Potential Biological Determinants of Autism Spectrum Disorders: From Neuroinflammation to Kynurenines Pathway

• DOI: 10.20944/preprints202007.0425.v1
• Publication Date: 2020-07-20T09:17:21Z
• Authors: Rosa Savino; Marco Carotenuto; Anna N. Polito; Sofia Di Noia; Marzia Albenzio; Alessia Scarinci; Antonio Ambrosi; Francesco Sessa; Nicola Tartaglia; Giovanni Messina
• Keywords: Kynurenine pathway; Excitotoxicity

Autism Spectrum Disorder etiopathogenesis is still unclear and no effective preventive treatment measures have been identified. Research has focused on the potential role of neuroinflammation kynurenine pathway. Here we review nature these interactions. Pre-natal or neonatal infections would induce microglial activation, with secondary consequences behavior, cognition neurotransmitter networks. Peripherally, higher levels pro-inflammatory cytokines anti-brain antibodies Increased frequency autoimmune diseases, allergies, recurring demonstrated both in autistic patients their relatives. Genetic studies, also, identified some important polymorphisms chromosome loci related to human leukocyte antigen (HLA) system. The persistence immune-inflammatory deregulation lead mitochondrial dysfunction oxidative stress, creating a self-sustaining cytotoxic loop. Chronic inflammation activates pathway increase neurotoxic metabolites excitotoxicity, causing long-term changes glutamatergic system, trophic support synaptic function. Furthermore, overactivation kynurenine’s branch induces depletion melatonin serotonin worsening ASD symptoms. In this scenario, appears as pharmacological target treat prevent ASD. Thus, genetically predisposed subjects aberrant neurodevelopment may derives from complex interplay between inflammatory process, dysfunction, stress overexpression. To validate previous hypothesis new translational research approach necessary.