Transactivation Response DNA-Binding Protein of 43 (TDP-43) and Glial Cell Roles in Neurological Disorders

Abstract

The trans-activation response DNA-binding protein of 43kDa (TDP-43) is involved in the pathogenesis of multiple brain disorders. As scientists are unraveling TDP-43 function and its impact on various diseases, we have begun to subcategorize them into TDP-43 proteinopathies. Furthermore, glial cell dysfunction contributes to various disorders, and TDP-43 is involved with glial cells via multiple pathways (direct or indirect) that aggravate the pathophysiology of such disorders. We are only now discovering and understanding the vast and diverse roles TDP-43 plays on neuronal cells and its effects on gliosis and neurodegenerative pathologies. It has multiple roles: mRNA maturation and splicing, transporting and maintaining mRNA stability, a component of stress granules and ubiquitination of dysfunctional or misfolded proteins, transcription of microtubule “Futsch” protein, and a role in maintaining synapse integrity and possibly more as we continue to research and uncover the labyrinth of the neuronal network. TDP-43 could also have a detrimental impact on glial cell activation and pathophysiology in diseases where TDP-43 is associated with its pathogenesis. We will review the pathophysiology of various neurological disorders that are associated with the alteration of the TDP-43 levels along with glial cell activation. Further, multiple diseases have glial cell participation in the pathogenesis, and the role of TDP-43 has not yet been investigated. We, therefore, explore those disorders in the context of both TDP-43 and glial cells involvement. This step will enhance the understanding of neurodegeneration where further research could prompt curative modalities with the advancement of technology.