Research Articles Base: Neurophysiology

The role of tau in neurodegenerative brain disease

“Different types of tau degeneration associated with different brain diseases”   INTRODUCTION             Tau is a protein that maintains the structure and function of the basic cells of the brain and nervous system, the neuron. Normal tau protein helps bind and stabilize microtubules, which are part of the internal, skeleton-like structure of the cell. It has long been thought by scientists that disaster would strike anyone whose tau was disrupted, and it seems that studies in the past few years have proved just that. Many neurological degeneration incidents are said to be related to the disruption of the tau. The degeneration of tau is associated with Alzheimer’s disease and frontotemporal dementia among many other neurological diseases. This paper will attempt to look into the different types of tau degeneration associated with different brain diseases, with a specific look on its role in Alzheimer’s disease.   BODY Alzheimer’s disease is characterized by progressive loss of short term memory followed by general loss of cognitive function and death in middle age. The cause of the neuronal degeneration in Alzheimer’s disease is still unsettled. The cytopathologic hallmarks of the disease are intracellular neurofibrillary tangles, made up in part of hyperphosphorylated forms of the tau protein that normally binds to microtubules, and extracellular senile plaques, which have a core of beta amyloid surrounded by altered nerve fibers and reactive cells (2001). The neurofibrillary tangles consist of filamentous inclusions formed within the cytoplasm of neurons. In addition, neurofibrillary tangles were specifically labeled with antibodies directed against phosphorylated epitopes of tau and a neurofilament subunit ( 1995). In the past, research could not fully explain the relationship between plaques and tangles. Most data suggested that the lesions formed independently of one another. However, the most recent findings suggest that the two principal neuropathological features of Alzheimer’s disease may he interrelated, with amyloid plaques giving rise to neurofibrillary tangles (2003). Researchers have long thought that the composition of the tangles and paired helical filaments might reveal important information about what causes Alzheimer’s and causes the loss of neurons. Recent findings indicate that the loss of neurons and the formation of tangles progress together ( 2001). The twisted threads inside nerve cells that make up neurofibrillary tangles are comprised of a hyperphosphorylated form of a normal protein called tau. An abnormally phosphorylated isoform of the protein tau, associated with microtubules, is therefore the major and critical component of paired helical filaments (1993). Current studies also show that beta amyloid activates caspases, which are enzymes that target proteins during apoptosis, or genetically controlled cell death. A team of researchers observed that one end of the tau protein seemed to block the formation of tangles and hypothesized that caspases might target tan during apoptosis. The action could remove the end fragment and cause tau to more easily form tangles (2003). Normal tau proteins are important to the central nervous system because they help bind and stabilize microtubules, which are a part of the internal support structure of cells. Microtubules might be pictured as railroad tracks in healthy neurons that allow nutrients and molecules to pass from the cell body to the ends of its axon. An axon is a long, thin structure that extends out from the body of a cell to allow connections with other neurons (1996). In Alzheimer’s disease, normal tau is chemically changed, and this altered form can no longer hold together the track-like support structure of microtubules. As a result of this chemical alteration, microtubules collapse. This breakdown in the transport system of neurons may significantly disrupt communication between nerve cells and eventually lead to the death of the neurons ( 2001). There are new studies which show that mutations in the gene that encodes the tau protein underlie some forms of fronto-temporal dementia (FTD) and other forms of neurodegeneration. Though less common than Alzheimer’s disease, FTD is one of the most prevalent forms of dementia, accounting for 5 to 10 percent of cases (1998). FTD with Parkinsonism has been linked to tau gene mutations on chromosome 17. Numerous other neurological diseases have prominent tau pathologies. The presence of tau within the cells may be enough to induce the onset, or progression, of Pick’s disease, progressive supranuclear palsy, Alzheimer’s disease, and other neurodegenerative diseases found to have prominent tau pathology (2001). Tau appears to be the marker of the severity of the disease. The percentage of neurons with neurofibrillary tangles increases with the severity of the disease (2001).   CONCLUSION The tau protein, aggregating into twisted tangles inside neurons, is thought by some researchers to have a causative role in the disease process of Alzheimer’s disease and other neurodegenerative diseases. Recent studies and findings have indicated that indeed tau plays a big role. In Alzheimer’s disease, tau is chemically altered, which causes microtubules to fall apart. The collapse of microtubules disrupts connections over which cell communications are transported. Possibly this breakthrough in tau will lead to better understanding of the protein and how it contributes to the death of nerve cells and somehow help also in the understanding of many neurodegenerative diseases such as Alzheimer’s disease. Tau has been left out in the cold too long and was only lately been pointed out as a culprit in many neurodegenerative diseases. Much more research is required to completely understand this very complex protein and how it is regulated in the brain of persons with neurodegenerative diseases like Alzheimer’s disease as well as in the normal brain.   Credit:ivythesis.typepad.com

The role of tau in neurodegenerative brain disease

“Different types of tau degeneration associated with different brain diseases” INTRODUCTION Tau is a protein that mainta...