Structural Transition, Function and Dysfunction of TDP-43 in Neurodegenerative Diseases
Keywords:Als, Ftd, Neurodegenerative diseases, Protein misfolding, Protein aggregation, Rna metabolism, Tdp-43, Tdp-43 proteinopathies
AbstractAltered cellular localization and pathologic aggregation of RNA binding proteins (RPBs) containing low complexity regions (LCRs) is a hallmark of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Given the importance of RBPs in maintaining a healthy RNA homeostasis, a common mechanism in disease progression is the loss of RNA-related cellular functions. In this review, we summarize and discuss the knowledge gained in the recent years on the molecular mechanisms of TDP-43 proteinopathies that comprise a set of neurodegenerative diseases characterized by the mislocalization and aggregation of the RNA-binding protein TDP-43. Based on biophysical, biochemical and in vivo data, we highlight pathways that are misregulated early in disease and contribute to its progression, thereby representing attractive therapeutic targets.
How to Cite
T. Afroz, M. Pérez-Berlanga, M. Polymenidou, Chimia 2019, 73, 380, DOI: 10.2533/chimia.2019.380.
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