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Structure and pathology of tau protein in Alzheimer disease.

Kolarova M, García-Sierra F, Bartos A, Ricny J, Ripova D - Int J Alzheimers Dis (2012)

Bottom Line: In connection with the global trend of prolonging human life and the increasing number of elderly in the population, the AD becomes one of the most serious health and socioeconomic problems of the present.The molecular mechanisms governing tau aggregation are mainly represented by several posttranslational modifications that alter its structure and conformational state.Evidences about the clinicopathological significance of phosphorylated and truncated tau have been documented during the progression of AD as well as their capacity to exert cytotoxicity when expressed in cell and animal models.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Biochemistry and Brain Pathophysiology and AD Center, Prague Psychiatric Center, Ústavní 91, 181 03 Prague 8, Czech Republic.

ABSTRACT
Alzheimer's disease (AD) is the most common type of dementia. In connection with the global trend of prolonging human life and the increasing number of elderly in the population, the AD becomes one of the most serious health and socioeconomic problems of the present. Tau protein promotes assembly and stabilizes microtubules, which contributes to the proper function of neuron. Alterations in the amount or the structure of tau protein can affect its role as a stabilizer of microtubules as well as some of the processes in which it is implicated. The molecular mechanisms governing tau aggregation are mainly represented by several posttranslational modifications that alter its structure and conformational state. Hence, abnormal phosphorylation and truncation of tau protein have gained attention as key mechanisms that become tau protein in a pathological entity. Evidences about the clinicopathological significance of phosphorylated and truncated tau have been documented during the progression of AD as well as their capacity to exert cytotoxicity when expressed in cell and animal models. This paper describes the normal structure and function of tau protein and its major alterations during its pathological aggregation in AD.

No MeSH data available.


Related in: MedlinePlus

Amino acid sequence of the longest tau isoform (441 amino acids). N1 and N2: the polypeptide sequences encoded by exons 2 and 3; P1 and P2: proline-rich regions; R1–R4: microtubule-binding domains encoded by exons 9–12; 275VQIINK280 and 306VQIVYK311: sequences with β-structure (modified by [13]).
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fig1: Amino acid sequence of the longest tau isoform (441 amino acids). N1 and N2: the polypeptide sequences encoded by exons 2 and 3; P1 and P2: proline-rich regions; R1–R4: microtubule-binding domains encoded by exons 9–12; 275VQIINK280 and 306VQIVYK311: sequences with β-structure (modified by [13]).

Mentions: Tau protein belongs to a group of proteins referred to as Microtubule-Associated Proteins (MAPs), that in common are heat resistant and limited affected by acid treatment without loss their function [8]. This property observed in tau is due to a very low content of secondary structure. In fact, a number of biophysical studies revealed that tau is a prototypical “natively unfolded” protein [9–11]. Since disordered proteins tend to be highly flexible and have variable conformations, they have not been amenable for structure analysis by crystallography so far. Thus nuclear magnetic resonance spectroscopy is the only plausible method that allows a description of their conformations and dynamics with high resolution [12]. Now it is possible to obtain the complete backbone assignment of 441-residue tau (the longest tau isoform found in the human central nervous system; Figure 1). This makes it possible to probe the structure and dynamics of the full-length soluble protein and determine the residues involved in the interaction between tau and microtubules at single residue resolution [13].


Structure and pathology of tau protein in Alzheimer disease.

Kolarova M, García-Sierra F, Bartos A, Ricny J, Ripova D - Int J Alzheimers Dis (2012)

Amino acid sequence of the longest tau isoform (441 amino acids). N1 and N2: the polypeptide sequences encoded by exons 2 and 3; P1 and P2: proline-rich regions; R1–R4: microtubule-binding domains encoded by exons 9–12; 275VQIINK280 and 306VQIVYK311: sequences with β-structure (modified by [13]).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368361&req=5

fig1: Amino acid sequence of the longest tau isoform (441 amino acids). N1 and N2: the polypeptide sequences encoded by exons 2 and 3; P1 and P2: proline-rich regions; R1–R4: microtubule-binding domains encoded by exons 9–12; 275VQIINK280 and 306VQIVYK311: sequences with β-structure (modified by [13]).
Mentions: Tau protein belongs to a group of proteins referred to as Microtubule-Associated Proteins (MAPs), that in common are heat resistant and limited affected by acid treatment without loss their function [8]. This property observed in tau is due to a very low content of secondary structure. In fact, a number of biophysical studies revealed that tau is a prototypical “natively unfolded” protein [9–11]. Since disordered proteins tend to be highly flexible and have variable conformations, they have not been amenable for structure analysis by crystallography so far. Thus nuclear magnetic resonance spectroscopy is the only plausible method that allows a description of their conformations and dynamics with high resolution [12]. Now it is possible to obtain the complete backbone assignment of 441-residue tau (the longest tau isoform found in the human central nervous system; Figure 1). This makes it possible to probe the structure and dynamics of the full-length soluble protein and determine the residues involved in the interaction between tau and microtubules at single residue resolution [13].

Bottom Line: In connection with the global trend of prolonging human life and the increasing number of elderly in the population, the AD becomes one of the most serious health and socioeconomic problems of the present.The molecular mechanisms governing tau aggregation are mainly represented by several posttranslational modifications that alter its structure and conformational state.Evidences about the clinicopathological significance of phosphorylated and truncated tau have been documented during the progression of AD as well as their capacity to exert cytotoxicity when expressed in cell and animal models.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Biochemistry and Brain Pathophysiology and AD Center, Prague Psychiatric Center, Ústavní 91, 181 03 Prague 8, Czech Republic.

ABSTRACT
Alzheimer's disease (AD) is the most common type of dementia. In connection with the global trend of prolonging human life and the increasing number of elderly in the population, the AD becomes one of the most serious health and socioeconomic problems of the present. Tau protein promotes assembly and stabilizes microtubules, which contributes to the proper function of neuron. Alterations in the amount or the structure of tau protein can affect its role as a stabilizer of microtubules as well as some of the processes in which it is implicated. The molecular mechanisms governing tau aggregation are mainly represented by several posttranslational modifications that alter its structure and conformational state. Hence, abnormal phosphorylation and truncation of tau protein have gained attention as key mechanisms that become tau protein in a pathological entity. Evidences about the clinicopathological significance of phosphorylated and truncated tau have been documented during the progression of AD as well as their capacity to exert cytotoxicity when expressed in cell and animal models. This paper describes the normal structure and function of tau protein and its major alterations during its pathological aggregation in AD.

No MeSH data available.


Related in: MedlinePlus