Structural Transition, Function and Dysfunction of TDP-43 in Neurodegenerative Diseases

Area of Science:

• Neurobiology
• Molecular Biology
• Genetics

Background:

• Altered cellular localization and aggregation of RNA binding proteins (RBPs) with low complexity regions (LCRs) characterize neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
• The dysregulation of RBPs disrupts RNA homeostasis, a critical cellular function, and contributes to disease progression.

Purpose of the Study:

• To review and discuss recent advancements in understanding the molecular mechanisms underlying TDP-43 proteinopathies.
• To identify early misregulated pathways in TDP-43 proteinopathies as potential therapeutic targets.

Main Methods:

• Review of biophysical data.
• Review of biochemical data.
• Review of in vivo data.

Main Results:

• TDP-43 proteinopathies are characterized by the mislocalization and aggregation of the RNA-binding protein TDP-43.
• Early disease pathways that are misregulated have been identified.

Conclusions:

• Understanding the molecular mechanisms of TDP-43 proteinopathies is crucial for developing effective treatments.
• Targeting early misregulated pathways in TDP-43 proteinopathies holds promise for therapeutic intervention.