Misregulation of tau alternative splicing in neurodegeneration and dementia

Abstract

Tau is a microtubule-associated protein that fulfills several functions critical for neuronal formation and health. Tau discharges its functions by producing multiple isoforms via intricately regulated alternative splicing. These isoforms modulate tau function in normal brain by altering the domains of the protein, thereby influencing its conformation and post-translational modifications and hence its affinity for microtubules and other ligands. Disturbances in tau expression result in disruption of the neuronal cytoskeleton and formation of pathological tau structures (neurofibrillary tangles) found in brains of dementia sufferers. More specifically, aberrations in tau splicing regulation directly cause several neurodegenerative diseases that lead to dementia. This review briefly presents our cumulative knowledge of tau splicing regulation in connection with the alterations in tau splicing seen in neurodegeneration.