The MAPT gene represents a significant area of study in human biology, particularly concerning brain health. This gene carries instructions executed within our cells. Understanding this gene provides insights into normal biological processes and the development of certain conditions affecting the brain.
Understanding the MAPT Gene
The MAPT gene, or Microtubule Associated Protein Tau gene, is located on human chromosome 17, specifically at band 17q21.31. It serves as the blueprint for producing the tau protein. The MAPT gene has 16 exons, with at least six undergoing alternative splicing.
The human brain produces six different versions, or isoforms, of the tau protein. These isoforms range in size from 352 to 441 amino acids. Their differences include the presence of zero, one, or two 29-amino acid inserts at the N-terminal end and either three or four repeat regions at the C-terminal end. This variability results from alternative splicing of exons 2, 3, and 10.
Tau Protein’s Role in a Healthy Brain
Tau protein is abundant in the central nervous system, particularly within the axons of neurons. Its primary function involves interacting with tubulin to stabilize microtubules and promote their assembly. Microtubules are rigid, hollow fibers that form part of the cell’s internal structural framework, known as the cytoskeleton.
These microtubules act like “railroad tracks” within neurons, facilitating the transport of essential components such as nutrients, vesicles, and other molecules to the axon terminals. Tau helps maintain the structural integrity of these tracks, ensuring efficient transport and communication within brain cells. The proper balance between tau isoforms, specifically those with three versus four microtubule-binding repeats, is important for normal neuronal function. While tau is predominantly found in axons, it also plays a role in dendrites.
MAPT Gene and Neurodegeneration
Aberrations in the MAPT gene or modifications to the tau protein can lead to a group of neurodegenerative diseases collectively known as tauopathies. In these conditions, the tau protein detaches from microtubules and undergoes abnormal changes, such as hyperphosphorylation. This hyperphosphorylation causes tau to misfold and aggregate into insoluble clumps called neurofibrillary tangles (NFTs) inside neurons.
These tangles disrupt the internal transport system of neurons, impairing the movement of vital substances and affecting synaptic function. This disruption leads to neuronal dysfunction and the death of brain cells. While tau tangles are a characteristic feature of Alzheimer’s Disease (AD), mutations in the MAPT gene are a direct cause of certain forms of Frontotemporal Dementia (FTD), Progressive Supranuclear Palsy (PSP), and Corticobasal Degeneration (CBD). Over 50 different pathogenic MAPT mutations have been identified, leading to a variable range of cognitive, behavioral, and motor deficits.
Advancements in MAPT Research
Current research on the MAPT gene and tau protein focuses on developing tools for diagnosis and potential therapeutic strategies. Scientists are working on identifying biomarkers in blood and cerebrospinal fluid, which can detect tau pathology in living individuals. These advancements offer the potential for earlier and more accurate diagnoses of tauopathies, even before symptoms become apparent.
Various therapeutic approaches are under investigation to target tau pathology. These strategies include methods to prevent tau aggregation, clear existing tangles, or reduce the production of abnormal tau. Some research explores stabilizing microtubules to counteract the effects of tau detachment. Novel techniques such as gene-editing to correct MAPT mutations and immunotherapies are also being explored as potential future treatments. These ongoing research efforts hold promise for developing effective treatments to slow or halt the progression of neurodegenerative diseases linked to tau dysfunction.