The Emerging Roles of MicroRNAs in the Pathogenesis of Frontotemporal Dementia–Amyotrophic Lateral Sclerosis (FTD-ALS) Spectrum Disorders

Abstract

Increasing evidence suggests that frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) share some clinical, pathological, and molecular features as part of a common neurodegenerative spectrum disorder. In recent years, enormous progress has been made in identifying both pathological proteins and genetic mutations associated with FTD-ALS. However, the molecular pathogenic mechanisms of disease onset and progression remain largely unknown. Recent studies have uncovered unexpected links between FTD-ALS and multiple aspects of RNA metabolism, setting the stage for further understanding of the disorder. Here, the authors will focus on microRNAs and review the emerging roles of these small RNAs in several aspects of FTD-ALS pathogenesis.

Keywords::

• ALS
• C9ORF72
• CHMP2B
• FTD
• FUS
• MicroRNA
• neurodegeneration
• progranulin
• TDP-43

ACKNOWLEDGMENTS

We thank S. Ordway and Gao laboratory members for comments and discussions. This work was supported by the National Institutes of Health (R01 NS057553, R01 NS066586, and R21 NS077294 to F.-B.G.).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.