Tau-441, (2N4R), P301L mutant

Tau is a family of major neuronal microtubule associated proteins that are found in the neurofibrillary tangles (NFT) in Alzheimer's disease. Tau promotes the assembly and maintains the structure of microtubules in neuronal cells1,2,[3]. The Tau proteins are derived from alternative mRNA splice variants that originate from a single gene and result in mature proteins that vary in size from 352 to 441 amino acids (3[6].8 to 4[5].9 kDa). There are six Tau isoforms, that differ from one another in having three or four microtubule binding repeats (R) of 31-32 amino acids each, and two, one or none amino terminal inserts (N) of 29 amino acids each[4]. While the fetal brain contains a single isoform of tau (Tau-352) the adult brain has several isoforms all derived from a single gene by alternative mRNA splicing[5]. Mutations in the Tau gene are known to cosegregate with the disease in frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17)[6]. Four of the FTDP-17 tau mutations, R406W, V337M, G272V, and P301L, result in tau proteins that are more favorable substrates for phosphorylation by brain protein kinases than the wild-type tau.