Big Tau: What We Know, and We Need to Know

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Tau is a microtubule-associated protein (MAP) with multiple isoforms.
• Big tau is a unique, larger isoform (110 kDa) containing exon 4a, expressed in specific adult neurons and CNS regions.
• Big tau exhibits developmental transition from low-molecular-weight (LMW) tau during the postnatal period.

Purpose of the Study:

• To explore the under-researched physiological properties and pathological implications of Big tau.
• To highlight the importance of understanding Big tau's role in neuronal health and disease.
• To propose potential functions of Big tau in improving axonal transport and preventing tau aggregation.

Main Methods:

• Review of existing literature on tau isoforms and Big tau.
• Comparative analysis of exon 4a conservation across species.
• Speculative analysis based on Big tau's structural characteristics.

Main Results:

• Big tau's exon 4a is structurally conserved across vertebrates, but sequence homology is limited outside Mammalia.
• Little progress has been made in elucidating Big tau's functions since its discovery.
• Big tau is expressed in adult peripheral nervous system (PNS) neurons and specific central nervous system (CNS) regions.

Conclusions:

• Big tau may play a role in enhancing axonal transport in projecting axons.
• Big tau has potential protective properties against pathological tau aggregation.
• Further investigation into Big tau is crucial for understanding neuronal function and disease pathogenesis.