What Is the Role of Stathmin-2 in Axonal Biology and Degeneration?

摘要

Stathmin-2 (STMN2) is a microtubule-associated protein that has a major role in axonal development and repair. STMN2 promotes microtubule instability necessary for normal axonal outgrowth and regeneration. The expression of STMN2 is strongly regulated by nuclear transactive response DNA-binding protein 43 kDA (TDP-43). This multifunctional nucleic acid binding protein is a primary component of insoluble cytoplasmic aggregates associated with several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) resulting in frontotemporal dementia (FTD). Recent evidence indicates that reduced nuclear TDP-43 function leads to improper splicing of the gene encoding STMN2, leading to the production of a truncated protein. This finding provides a mechanistic link between TDP-43 proteinopathies and axonal degeneration.