Tau protein

A protein associated with microtubule stabilization and neurodegenerative diseases

Tau protein is a protein that plays a critical role in the stabilization of microtubules in neurons. It is predominantly found in the central nervous system and is associated with several neurodegenerative diseases, collectively known as tauopathies.

Structure and Function

Tau protein is a member of the microtubule-associated proteins (MAPs) family. It is primarily expressed in neurons, where it binds to and stabilizes microtubules, which are essential components of the cytoskeleton. Microtubules are involved in maintaining cell shape, enabling intracellular transport, and facilitating cell division.

Tau protein is encoded by the MAPT gene located on chromosome 17. The protein undergoes alternative splicing, resulting in six isoforms in the adult human brain. These isoforms differ in the number of microtubule-binding repeats and the presence of N-terminal inserts, which influence their binding affinity to microtubules.

Role in Neurodegenerative Diseases

Tau protein is implicated in a group of neurodegenerative disorders known as tauopathies. The most well-known of these is Alzheimer's disease, where abnormal hyperphosphorylation of tau leads to the formation of neurofibrillary tangles (NFTs). These tangles disrupt neuronal function and are a hallmark of the disease.

Other tauopathies include:

• Progressive supranuclear palsy
• Corticobasal degeneration
• Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17)

In these conditions, tau protein undergoes pathological changes, including hyperphosphorylation, truncation, and aggregation, leading to neuronal dysfunction and cell death.

Pathophysiology

The pathophysiological mechanisms of tau-related neurodegeneration involve several processes:

• Hyperphosphorylation: Abnormal phosphorylation of tau reduces its affinity for microtubules, causing it to detach and aggregate into insoluble filaments.
• Aggregation: Detached tau proteins aggregate into paired helical filaments (PHFs) and straight filaments, which form the core of neurofibrillary tangles.
• Cellular Dysfunction: The accumulation of tau aggregates disrupts cellular processes, including axonal transport, synaptic function, and neuronal communication.

Research and Therapeutic Approaches

Research into tau protein focuses on understanding its normal function, the mechanisms of its pathological transformation, and developing therapeutic strategies to prevent or reverse tau-related neurodegeneration.

Therapeutic approaches include:

• Tau-targeting drugs: Small molecules or antibodies that inhibit tau aggregation or promote its clearance.
• Gene therapy: Techniques to modulate tau expression or correct mutations in the MAPT gene.
• Phosphorylation inhibitors: Compounds that prevent abnormal phosphorylation of tau.

Images

File:Tau protein structure.png

Diagram of tau protein structure showing microtubule-binding domains.

File:Neurofibrillary tangles.png

Histological image of neurofibrillary tangles in Alzheimer's disease.

Related pages

• Microtubule
• Neurodegenerative disease
• Alzheimer's disease
• Frontotemporal dementia