Tau Phosphorylation and Aggregation as a Therapeutic Target in Tauopathies

被引:17
作者
Badiola, Nahuai [1 ]
Suarez-Calvet, Marc [1 ]
Lleo, Alberto [1 ]
机构
[1] Univ Autonoma Barcelona, Serv Neurol, Hosp St Pau, E-08193 Barcelona, Spain
关键词
Tau; tauopathies; Alzheimer; frontotemporal dementia; kinase inhibitors; dementia; immunization; MICROTUBULE-ASSOCIATED PROTEIN; PROGRESSIVE SUPRANUCLEAR PALSY; GLYCOGEN-SYNTHASE KINASE-3; PAIRED HELICAL FILAMENTS; CYCLIN-DEPENDENT KINASE-5; NEUROFIBRILLARY TANGLE FORMATION; MULTIPLE SYSTEM TAUOPATHY; RESONANCE ENERGY-TRANSFER; ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA;
D O I
10.2174/187152710793237403
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Tauopathies are neurodegenerative diseases characterized by insoluble hyperphosphorylated deposits of the microtubule-associated protein tau in the central nervous system. In these disorders, tau is believed to cause neurodegeneration and neuronal loss due to the loss of function of the normal protein, and/or the gain of toxic properties by generating multimeric species. The obstacles found in amyloid-based therapies in Alzheimer's disease, the most common tauopathy, have stimulated the search for alternative targets, including tau. In this article, we review the strategies aimed at reducing tau phosphorylation and aggregation as a target for drug intervention in tauopathies.
引用
收藏
页码:727 / 740
页数:14
相关论文
共 226 条
[91]   Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17 [J].
Hutton, M ;
Lendon, CL ;
Rizzu, P ;
Baker, M ;
Froelich, S ;
Houlden, H ;
Pickering-Brown, S ;
Chakraverty, S ;
Isaacs, A ;
Grover, A ;
Hackett, J ;
Adamson, J ;
Lincoln, S ;
Dickson, D ;
Davies, P ;
Petersen, RC ;
Stevens, M ;
de Graaff, E ;
Wauters, E ;
van Baren, J ;
Hillebrand, M ;
Joosse, M ;
Kwon, JM ;
Nowotny, P ;
Che, LK ;
Norton, J ;
Morris, JC ;
Reed, LA ;
Trojanowski, J ;
Basun, H ;
Lannfelt, L ;
Neystat, M ;
Fahn, S ;
Dark, F ;
Tannenberg, T ;
Dodd, PR ;
Hayward, N ;
Kwok, JBJ ;
Schofield, PR ;
Andreadis, A ;
Snowden, J ;
Craufurd, D ;
Neary, D ;
Owen, F ;
Oostra, BA ;
Hardy, J ;
Goate, A ;
van Swieten, J ;
Mann, D ;
Lynch, T .
NATURE, 1998, 393 (6686) :702-705
[92]   Transcriptional and conformational changes of the tau molecule in Alzheimer's disease [J].
Hyman, BT ;
Augustinack, JC ;
Ingelsson, M .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2005, 1739 (2-3) :150-157
[93]  
Imahori K, 1997, J BIOCHEM, V121, P179
[94]   Increased risk for frontotemporal dementia through interaction between tau polymorphisms and apolipoprotein E ε4 [J].
Ingelson, M ;
Fabre, SF ;
Lilius, L ;
Andersen, C ;
Viitanen, M ;
Almkvist, O ;
Wahlund, LO ;
Lannfelt, L .
NEUROREPORT, 2001, 12 (05) :905-909
[95]   Early Aβ accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain [J].
Ingelsson, M ;
Fukumoto, H ;
Newell, KL ;
Growdon, JH ;
Hedley-Whyte, ET ;
Frosch, MP ;
Albert, MS ;
Hyman, BT ;
Irizarry, MC .
NEUROLOGY, 2004, 62 (06) :925-931
[96]   Mechanisms of tau-induced neurodegeneration [J].
Iqbal, Khalid ;
Liu, Fei ;
Gong, Cheng-Xin ;
Alonso, Alejandra del C. ;
Grundke-Iqbal, Inge .
ACTA NEUROPATHOLOGICA, 2009, 118 (01) :53-69
[97]   Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform [J].
Ishihara, T ;
Hong, M ;
Zhang, B ;
Nakagawa, Y ;
Lee, MK ;
Trojanowski, JQ ;
Lee, VMY .
NEURON, 1999, 24 (03) :751-762
[98]   DIMINISHED GLUCOSE-TRANSPORT IN ALZHEIMERS-DISEASE - DYNAMIC PET STUDIES [J].
JAGUST, WJ ;
SEAB, JP ;
HUESMAN, RH ;
VALK, PE ;
MATHIS, CA ;
REED, BR ;
COXSON, PG ;
BUDINGER, TF .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1991, 11 (02) :323-330
[99]   TAU Haplotype and the Saitohin Q7R Gene Polymorphism Do Not Influence CSF Tau in Alzheimer's Disease and Are Not Associated with Frontotemporal Dementia or Parkinson's Disease [J].
Johansson, Annica ;
Zetterberg, Henrik ;
Hakansson, Anna ;
Nissbrandt, Hans ;
Blennow, Kaj .
NEURODEGENERATIVE DISEASES, 2005, 2 (01) :28-35
[100]   Clinicopathologic analysis of frontotemporal and corticobasal degenerations and PSP [J].
Josephs, KA ;
Petersen, RC ;
Knopman, DS ;
Boeve, BF ;
Whitwell, JL ;
Duffy, JR ;
Parisi, JE ;
Dickson, DW .
NEUROLOGY, 2006, 66 (01) :41-48