Proteomic and Microscopic Strategies towards the Analysis of the Cytoskeletal Networks in Major Neuropsychiatric Disorders

Abstract

Mental health disorders have become worldwide health priorities. It is estimated that in the next 20 years they will account for a 16 trillion United State dollars (US$) loss. Up to now, the underlying pathophysiology of psychiatric disorders remains elusive. Altered cytoskeleton proteins expression that may influence the assembly, organization and maintenance of cytoskeletal integrity has been reported in major depressive disorders, schizophrenia and to some extent bipolar disorders. The use of quantitative proteomics, dynamic microscopy and super-resolution microscopy to investigate disease-specific protein signatures holds great promise to improve our understanding of these disorders. In this review, we present the currently available quantitative proteomic approaches use in neurology, gel-based, stable isotope-labelling and label-free methodologies and evaluate their strengths and limitations. We also reported on enrichment/subfractionation methods that target the cytoskeleton associated proteins and discuss the need of alternative methods for further characterization of the neurocytoskeletal proteome. Finally, we present live cell imaging approaches and emerging dynamic microscopy technology that will provide the tools necessary to investigate protein interactions and their dynamics in the whole cells. While these areas of research are still in their infancy, they offer huge potential towards the understanding of the neuronal network stability and its modification across neuropsychiatric disorders.

iTRAQ‐Based Proteomic Analysis Reveals Protein Profile in Plasma from Children with Autism

“…For example, expression of FAK (focal adhesion kinase) was diminished in autistic lymphoblasts and overexpression of FAK in these cells restored the adhesion and migration defects . Besides ASDs, change in cytoskeleton proteins expression has been reported in other psychiatric disorders . In addition, recent genetic studies demonstrate that alterations in synaptic genes including those encoding cell adhesion molecules and their interaction partners play important roles in the pathogenesis of ASD .…”

Beyond Neuronal Microtubule Stabilization: MAP6 and CRMPS, Two Converging Stories

“…In further support of the validity of this model, subsequent studies revealed defects in MAP6 expression in humans presenting developmental delay, corpus callosum dysgenesis, autistic or schizophrenic symptoms (Shimizu et al, 2006;Choi et al, 2009;Martins-de-Souza et al, 2009;Xiao et al, 2015;Coumans et al, 2016;Wei et al, 2016a,b;Chen et al, 2021).…”

The Role of the Microbiome-Brain-Gut Axis in the Pathogenesis of Depressive Disorder

“…Proteomic studies of the frontal cortex and anterior cingulate gyrus indicate the presence of abnormal cytoskeletal organization in depressed patients, which is associated with changes in the expression of, among others, glial fibrillary acidic protein (GFAP), tubulin isoforms or MAP proteins [72]. Suicide victims demonstrated the increased expression of mRNA and proteins such as TNF-alpha, IL-6 and IL1-beta in Brodmann's area 10, suggesting the involvement of pro-inflammatory cytokines in the pathogenesis of psychiatric disorders [73].…”