Emerging proteomic approaches to identify the underlying pathophysiology of neurodevelopmental and neurodegenerative disorders

Abstract

Proteomics is the large-scale study of the total protein content and their overall function within a cell through multiple facets of research. Advancements in proteomic methods have moved past the simple quantification of proteins to the identification of post-translational modifications (PTMs) and the ability to probe interactions between these proteins, spatially and temporally. Increased sensitivity and resolution of mass spectrometers and sample preparation protocols have drastically reduced the large amount of cells required and the experimental variability that had previously hindered its use in studying human neurological disorders. Proteomics offers a new perspective to study the altered molecular pathways and networks that are associated with autism spectrum disorders (ASD). The differences between the transcriptome and proteome, combined with the various types of post-translation modifications that regulate protein function and localization, highlight a novel level of research that has not been appropriately investigated. In this review, we will discuss strategies using proteomics to study ASD and other neurological disorders, with a focus on how these approaches can be combined with induced pluripotent stem cell (iPSC) studies. Proteomic analysis of iPSC-derived neurons have already been used to measure changes in the proteome caused by patient mutations, analyze changes in PTMs that resulted in altered biological pathways, and identify potential biomarkers. Further advancements in both proteomic techniques and human iPSC differentiation protocols will continue to push the field towards better understanding ASD disease pathophysiology. Proteomics using iPSC-derived neurons from individuals with ASD offers a window for observing the altered proteome, which is necessary in the future development of therapeutics against specific targets. Autism spectrum disorders

Nanoplasmonic immunosensor for the detection of SCG2, a candidate serum biomarker for the early diagnosis of neurodevelopmental disorder

“…The expression patterns of proteins reflect the biological functions of cells better than those of mRNA or DNA; thus, it is imperative to identify protein biomarkers 4 , 5 . A large-scale study of total protein was recently conducted to identify protein biomarkers for neurodevelopment disorders 6 . The detection of protein biomarkers can be performed using brain tissues and body fluids such as cerebral spinal fluid (CSF) or serum, but diagnosis using brain tissues is not common, except in special cases.…”

Proteomic insights into synaptic signaling in the brain: the past, present and future

“…Proteomics has long played an indispensable role in the discovery and verification of biomarkers for brain disorders [ 17 ], and studies are increasingly oriented towards exploring the pathological mechanisms underlying various brain disorders. In a recently published work, researchers found that the astrocytic cystine/glutamate antiporter system xc(-) regulated corticostriatal neurotransmission, and influenced social preference and repetitive behavior in mice, providing important clues toward the neural mechanisms related to ASD and obsessive–compulsive disorder [ 226 ].…”

“…We scrutinize the synaptic proteome in a functional context, look into the molecular mechanisms underlying brain disorders, and discuss the current opportunities, challenges, and trends in neuroproteomics. Proteomics approaches are widely used in the search for biomarkers of neurological and psychiatric disorders; however, these studies are beyond the scope of this review, and interested readers are referred to a recent review for an overview of this research field [ 17 ].…”

Molecular signatures from multi‐omics of autism spectrum disorders and schizophrenia

“…In addition, transcriptome analysis using RNA-sequencing of post mortem brains has found significant changes in synaptic as well as translation, immune, chromosome, and splicing-associated genes (Quesnel-Vallières et al, 2019). In contrast, the correlation between RNA and protein amounts is not always consistent (Murtaza et al, 2020). Thus, researchers must be cautious when interpreting the results of these experiments and carefully understand the differences between these methods.…”