iological roles since they are differentially expressed during development. In the fetal human brain, only the shortest tau isoform is present. In the peripheral nervous system, inclusion of exon 4a in the N-terminal half results in the expression of a higher molecular weight protein termed big tau. The presence of many serine/threonine, proline, and arginine/lysine/histine residues in tau molecule bestows unusual characters with potential to be hyperphosphorylated, very poor secondary structure and basic protein, which linked to its biological function and pathologic changes in the diseases. The main biological functions of tau known are to stimulate 
MT assembly and to stabilize MT structure. Tau binds to MTs through its MT-binding repeats. 4R-tau isoforms are more efficient at promoting MT assembly and have a great MT-binding affinity than do 3R-tau isoforms because the inter-repeat sequence between the first and second MT-binding repeats has more than twice the binding affinity of any other individual MT-binding repeats. Therefore, tau from fetal brain promotes microtubule assembly less efficiently than tau from adult brain. Alternative splicing of tau exon 10 Alternative splicing of pre-mRNA, the differential inclusion or exclusion of portions of a nascent transcript into the final protein-coding mRNA, is widely recognized to be a ubiquitous mechanism for controlling protein expression. More than 60% of mammalian pre-mRNA is alternatively spliced, and this process is widely prevalent in the nervous system. Splicing is catalyzed by the spliceosome, a macromolecular machine consisting of five small nuclear RNA molecules and as much as 150 proteins. Each of the five snRNAs assembles with proteins to form small nuclear ribonucleoprotein particles. A coordinated binding of the five snRNP to pre-mRNA results in the removal of each intron and the ligation of the flanking exons. Alternative splicing is controlled by multiple exonic and intronic cis-elements and trans-acting splicing MedChemExpress Neuromedin N factors. The element in an exon that increases inclusion of the alternatively spliced exon is called exonic splicing enhancer, and that decreases inclusion is called exonic splicing silencer. The element with similar function located in an intron is called intronic splicing enhancer or intronic splicing silencer. Cis-elements in tau exon 10 and intron 10 Most alternative spliced exons contain one weak splice site. However, PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19799681 tau exon 10 has two weak splice sites, a weak 5′ splice and a weak 3′ splice site. The exon is flanked by unusually large intron 9 and intron 10. These features of tau exon 10 lead to much complicated regulation. Several short cis-elements in exon 10 and intron 10, which modulate the use of the weak 5′ and 3′ splice sites, have been identified and extensively characterized. The 5′ end of exon 10 contains three ESEs: a SC35-like enhancer, a polypurine enhancer, and an A/C-rich enhancer . Following the ESEs region, there is an exon splicing silencer. In addition, the 3′ end of exon 10 contains another ESE sequence between the ESS and the 5′ splice site. In intron 10, there are bipartite elements composed of the ISS and the intronic splicing modulator . Deletion assay revealed opposite effects of the ISS and ISM on E10 splicing. Page 3 of 10 Molecular Neurodegeneration 2008, 3:8 http://www.molecularneurodegeneration.com/content/3/1/8 The ISM is not an enhancer by itself, but functions only in the presence of the ISS and counteracts ISS-mediated i