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.
Highlights
And up to recently, mental illnesses were not global health priorities when compared with infectious/contagious diseases and conditions such as cancers, cardiovascular disease, diabetes and chronic lung illnesses
The 2010 Global Burden of Disease (GBD) study has revealed that neuropsychiatric conditions were significantly responsible for the total disease burden in the world as measured in years lived with disability (YLD); depression being the most disabling disorder worldwide
This was nicely summarized by the review of Whiteford et al [1], which emphasized that mental health and substance use were the fifth leading disorder category of global disability-adjusted life-years (DALYs) accounting for 183.9 million DALYs and equivalent to 7.4% of total disease burden in 2010
Summary
And up to recently, mental illnesses were not global health priorities when compared with infectious/contagious diseases and conditions such as cancers, cardiovascular disease, diabetes and chronic lung illnesses. The report by the World Economic Forum and the Harvard School of Public Health estimated that in the 20 years mental health conditions alone will account for the loss of US$16 trillion, equivalent to 25% of global Gross domestic product (GDP) in 2010 [2]. Despite these critical data, up to now, molecular mechanisms underpinning neuropsychiatric disorders remain largely misunderstood and pursuing novel strategies for the treatment and even prevention of mental illness is of foremost importance. Beside reporting on the contribution of proteomics to quantitative discovery research in psychiatric disorders, we discuss the need of alternative methods for further characterization of the neurocytoskeletal proteome and present live cell dynamic microscopy technologies that will provide the tools necessary to investigate protein interactions and their dynamics in the whole cells
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