Dysfunctional proteins in neuropsychiatric disorders: From neurodegeneration to autism spectrum disorders

• Published in: Neurochemistry international 2020-12, Vol.141, p.104853-104853, Article 104853
• Main Authors: Jęśko, Henryk, Cieślik, Magdalena, Gromadzka, Grażyna, Adamczyk, Agata
• Format: Article
• Language: English
• Subjects: Alzheimer's disease (AD); Amyloid β (Aβ); Autism spectrum disorders (ASD); Microtubule-associated protein (MAP) tau; Parkinson's disease (PD); α-Synuclein (α-syn)
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2020.104853

Despite fundamental differences in disease course and outcomes, neurodevelopmental (autism spectrum disorders – ASD) and neurodegenerative disorders (Alzheimer's disease – AD and Parkinson's disease – PD) present surprising, common traits in their molecular pathomechanisms. Uncontrolled oligomerization and aggregation of amyloid β (Aβ), microtubule-associated protein (MAP) tau, or α-synuclein (α-syn) contribute to synaptic impairment and the ensuing neuronal death in both AD and PD. Likewise, the pathogenesis of ASD may be attributed, at least in part, to synaptic dysfunction; attention has also been recently paid to irregularities in the metabolism and function of the Aβ precursor protein (APP), tau, or α-syn. Commonly affected elements include signaling pathways that regulate cellular metabolism and survival such as insulin/insulin-like growth factor (IGF) – PI3 kinase – Akt – mammalian target of rapamycin (mTOR), and a number of key synaptic proteins critically involved in neuronal communication. Understanding how these shared pathomechanism elements operate in different conditions may help identify common targets and therapeutic approaches. •Synaptic deterioration gains recognition as an early element of neurodegeneration.•Synaptic pathology is the central element of autism spectrum disorders.•Autism and neurodegeneration share multiple aspects of pathomechanism.•These common elements include protein aggregation and deregulated signaling.