MAPT

Official Full Name

microtubule associated protein tau

Organism

Homo sapiens

Gene ID

4137

Background

This gene encodes the microtubule-associated protein tau (MAPT) whose transcript undergoes complex, regulated alternative splicing, giving rise to several mRNA species. MAPT transcripts are differentially expressed in the nervous system, depending on stage of neuronal maturation and neuron type. MAPT gene mutations have been associated with several neurodegenerative disorders such as Alzheimer's disease, Pick's disease, frontotemporal dementia, cortico-basal degeneration and progressive supranuclear palsy. [provided by RefSeq, Jul 2008]

Synonyms

TAU; FTD1; MSTD; PPND; DDPAC; MAPTL; MTBT1; MTBT2; tau-40; FTDP-17; PPP1R103; Tau-PHF6

Protein Sequence

MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQEPESGKVVQEGFLREPGPPGLSHQLMSGMPGAPLLPEGPREATRQPSGTGPEDTEGGRHAPELLKHQLLGDLHQEGPPLKGAGGKERPGSKEEVDEDRDVDESSPQDSPPSKASPAQDGRPPQTAAREATSIPGFPAEGAIPLPVDFLSKVSTEIPASEPDGPSVGRAKGQDAPLEFTFHVEITPNVQKEQAHSEEHLGRAAFPGAPGEGPEARGPSLGEDTKEADLPEPSEKQPAAAPRGKPVSRVPQLKARMVSKSKDGTGSDDKKAKTSTRSSAKTLKNRPCLSPKHPTPGSSDPLIQPSSPAVCPEPPSSPKYVSSVTSRTGSSGAKEMKLKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGL

Open

Approved Drug

Clinical Trial Drug

17 +

Discontinued Drug

Cat.No.	Product Name	Price
CSC-DC009218	Panoply™ Human MAPT Knockdown Stable Cell Line	Inquiry
CSC-SC009218	Panoply™ Human MAPT Over-expressing Stable Cell Line	Inquiry
CSC-RT2825	Human MAPT Knockout Cell Line-HCT116	Inquiry

Cat.No.	Product Name	Price
AD09672Z	Human MAPT adenoviral particles	Inquiry
LV00369Z	Human MAPT lentiviral particles	Inquiry
LV00370Z	Human MAPT lentiviral particles	Inquiry
LV00371Z	Human MAPT lentiviral particles	Inquiry

Cat.No.	Product Name	Price
SHH176951	shRNA set against Mouse Mapt(NM_010838.3)	Inquiry
SHH176829	shRNA set against Rat Mapt(NM_017212.2)	Inquiry
SHH176833	shRNA set against Mouse Mapt(NM_001038609.1)	Inquiry
SHH176897	shRNA set against Human MAPT(NM_001123066.3)	Inquiry
SHH232902	shRNA set against Mouse AF067063 (NM_001001449.2)	Inquiry
SHH245446	shRNA set against Mouse BC048507 (NM_001001185.3)	Inquiry
SHH338227	shRNA set against Human MAPT (NM_005910.5)	Inquiry
SHH338231	shRNA set against Mouse MAPT (NM_010838.3)	Inquiry
SHH338235	shRNA set against Rat MAPT (NM_017212.2)	Inquiry
SHW003189	shRNA set against Chicken MAPT (NM_001199193)	Inquiry

Cat.No.	Product Name	Price
RP00622	Recombinant Human MAPT (624-756aa, C-6His)	Inquiry

Cat.No.	Product Name	Price
CDCR378277	Rat Mapt ORF Clone(NM_017212.2)	Inquiry
MiUTR1M-06947	MAPT miRNA 3'UTR clone	Inquiry
MiUTR1M-01279	AF067063 miRNA 3'UTR clone	Inquiry
MiUTR1H-06106	MAPT miRNA 3'UTR clone	Inquiry
CDFR011263	Rat Mapt cDNA Clone(NM_017212.2)	Inquiry
CDFG018229	Mouse Mapt cDNA Clone(NM_001038609.1)	Inquiry
CDCS407729	Human MAPT ORF Clone (BC114948)	Inquiry
MiUTR1R-03691	MAPT miRNA 3'UTR clone	Inquiry
MiUTR4H-TG05364	MAPT miRNA 3'UTR clone	Inquiry
CDCR249722	Mouse Mapt ORF Clone(NM_010838.3)	Inquiry
CDCL211984	Mouse BC048507 ORF Clone(NM_001001185.3)	Inquiry
CDCL210781	Mouse AF067063 ORF Clone(NM_001001449.2)	Inquiry
CDCL130643	Human MAPT ORF clone (NM_001203252.1)	Inquiry
CDCL130641	Mouse MAPT ORF clone (NM_001203251.1)	Inquiry
CDCL130627	Human Mapt ORF clone (NM_001038609.1)	Inquiry
CDCB191325	Rabbit MAPT ORF clone (XM_008271646.1)	Inquiry
CDCB164664	Chicken MAPT ORF Clone (NM_001199193)	Inquiry

Detailed Information

The microtubule-associated protein tau (MAPT) is a major member of the microtubule-associated proteins (MAP) family. It is highly soluble and is encoded by a single gene on the long arm of chromosome 17. It is mainly distributed in the brain's frontal lobe, temporal lobe hippocampus and entorhinal region neuron axons, and its binding ability to axons is stronger than that of cell bodies or dendrites. MAPT acts primarily at the distal end of the axon, maintaining microtubule stability and the necessary flexibility. Tau proteins interact with tubulin to stabilize microtubules while driving Tubulin to assemble within microtubules. Tau proteins control the stability of microtubules through isomerization and phosphorylation.

MAPT and AD

Alzheimer's disease (AD) is the most common cause of dementia and is a type of degenerative disease in the central nervous system, with progressive cognitive impairment and memory impairment. The main pathological features of AD are senile plaques and neurofibrillary tangles. The core component of neurofibrillary tangles is double-helix filaments (PHFs) formed by abnormally modified Tau proteins. In patients with AD, the pathological changes of Tau protein are more strongly associated with amyloid (Aβ) and cognitive impairment, and the number of neurofibrillary tangles is directly related to the timing and extent of AD. Both in vivo and in vitro experiments have found that Tau protein is required for the toxic effects of Aβ. The phosphorylated Tau protein initially appears in the brainstem, especially the blue spot, followed by the midbrain marginal system in combination with the cortex, and finally the neocortex. The Aβ deposit is first in the combined cortex, then in the subcortical structure / deep gray matter / brain stem and cerebellum.

Figure 1. Diagram showing potential neuroprotective strategies to reduce tau aggregates.（Šimić Goran, et al. 2016）

Current treatment studies for Tau proteins include the following: 1) regulation of phosphorylation of Tau by inhibiting protein kinases such as GSK-3β, CDK5 and MARK and activating PP2A phosphatase; 2) in some Tau protein transgenic mice Use some anti-mitotic drugs such as paclitaxel or epothilone to stabilize microtubules; 3) Screening in vitro and at the cellular level, nitrogen aniline rhodamine, phenyl hydrazide, terpenoids, aminopyridines Compounds can inhibit the aggregation of Tau protein.

MAPT Gene Mutation

Tau protein gene MAPT mutations can lead to frontotemporal dementia, demonstrating that even without amyloid abnormalities, Tau protein can cause neuronal loss and clinical dementia. The MAPT gene has been found to have more than 40 different mutation sites, 50% related to FTLD, and clinical manifestations vary. Mutated MATP leads to impaired microtubule assembly, abnormal axonal transport and accelerated pathological Tau fiber aggregation. The age of onset is early (about 50 years old), and Parkinson's syndrome and eye movement disorders suggest MAPT mutations. Of the 51 patients with Parkinson's disease, 21 of the patients with PD had memory impairment, and the MAPT was mutated in the patient. The change was related to the medial memory code of the temporal lobe. These results demonstrate that common mutations in MAPT are not only associated with PD dementia, but also the potential differences in the underlying neural circuits in normal aging.

References:

Šimić Goran, Mirjana, B. L., Selina, W., Charles, H., Ivana, D., & Nataša, J. M., et al. (2016). Tau protein hyperphosphorylation and aggregation in alzheimer’s disease and other tauopathies, and possible neuroprotective strategies:. Biomolecules, 6(1), 6.
Miguel, M. , & Jes?Os, A. . (2014). The role of extracellular tau in the spreading of neurofibrillary pathology. Frontiers in Cellular Neuroscience, 8.
Zhang, C. C. , Zhu, J. X. , Wan, Y. , Tan, L. , Wang, H. F. , & Yu, J. T. , et al. (2017). Meta-analysis of the association between variants in mapt and neurodegenerative diseases. Oncotarget,8(27), 44994-45007.

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