Nuclear Tau and Its Potential Role in Alzheimer's Disease

被引:113
作者
Maina, Mahmoud Bukar [1 ,2 ]
Al-Hilaly, Youssra K. [1 ,3 ]
Serpell, Louise C. [1 ]
机构
[1] Univ Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England
[2] Gombe State Univ, Coll Med Sci, Dept Human Anat, Gombe 760, Nigeria
[3] Al Mustansiriyah Univ, Coll Sci, Dept Chem, Baghdad, Iraq
基金
英国医学研究理事会;
关键词
neurofibrillary tangles; Alzheimer's disease; tau; nucleolus; paired helical filament; nucleus; HUMAN NEUROBLASTOMA-CELLS; CENTRAL-NERVOUS-SYSTEM; NUCLEOLAR ORGANIZER REGIONS; PAIRED HELICAL FILAMENTS; HAMSTER OVARY CELLS; SINGLE-STRANDED-DNA; PROTEIN-TAU; IN-VITRO; NEUROFIBRILLARY DEGENERATION; NEURODEGENERATIVE DISEASES;
D O I
10.3390/biom6010009
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Tau protein, found in both neuronal and non-neuronal cells, forms aggregates in neurons that constitutes one of the hallmarks of Alzheimer's disease (AD). For nearly four decades, research efforts have focused more on tau's role in physiology and pathology in the context of the microtubules, even though, for over three decades, tau has been localised in the nucleus and the nucleolus. Its nuclear and nucleolar localisation had stimulated many questions regarding its role in these compartments. Data from cell culture, mouse brain, and the human brain suggests that nuclear tau could be essential for genome defense against cellular distress. However, its nature of translocation to the nucleus, its nuclear conformation and interaction with the DNA and other nuclear proteins highly suggest it could play multiple roles in the nucleus. To find efficient tau-based therapies, there is a need to understand more about the functional relevance of the varied cellular distribution of tau, identify whether specific tau transcripts or isoforms could predict tau's localisation and function and how they are altered in diseases like AD. Here, we explore the cellular distribution of tau, its nuclear localisation and function and its possible involvement in neurodegeneration.
引用
收藏
页码:2 / 20
页数:20
相关论文
共 130 条
[1]   Hyperphosphorylation induces self-assembly of τ into tangles of paired helical filaments/straight filaments [J].
Alonso, AD ;
Zaidi, T ;
Novak, M ;
Grundke-Iqbal, I ;
Iqbal, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (12) :6923-6928
[2]   Herpes simplex virus type 1 induces nuclear accumulation of hyperphosphorylated tau in neuronal cells [J].
Alvarez, Gema ;
Aldudo, Jesus ;
Alonso, Maria ;
Santana, Soraya ;
Valdivieso, Fernando .
JOURNAL OF NEUROSCIENCE RESEARCH, 2012, 90 (05) :1020-1029
[3]  
Alzheimer A, 1995, Clin Anat, V8, P429
[4]   STRUCTURE AND NOVEL EXONS OF THE HUMAN-TAU GENE [J].
ANDREADIS, A ;
BROWN, WM ;
KOSIK, KS .
BIOCHEMISTRY, 1992, 31 (43) :10626-10633
[5]   Tau gene alternative splicing: expression patterns, regulation and modulation of function in normal brain and neurodegenerative diseases [J].
Andreadis, A .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2005, 1739 (2-3) :91-103
[6]   Tau dephosphorylation at tau-1 site correlates with its association to cell membrane [J].
Arrasate, M ;
Pérez, M ;
Avila, J .
NEUROCHEMICAL RESEARCH, 2000, 25 (01) :43-50
[7]   Nuclear Translocation Uncovers the Amyloid Peptide Aβ42 as a Regulator of Gene Transcription [J].
Barucker, Christian ;
Harmeier, Anja ;
Weiske, Joerg ;
Fauler, Beatrix ;
Albring, Kai Frederik ;
Prokop, Stefan ;
Hildebrand, Peter ;
Lurz, Rudi ;
Heppner, Frank L. ;
Huber, Otmar ;
Multhaup, Gerhard .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289 (29) :20182-20191
[8]   CIS-ACTING SIGNALS AND TRANS-ACTING PROTEINS ARE INVOLVED IN TAU MESSENGER-RNA TARGETING INTO NEURITES OF DIFFERENTIATING NEURONAL CELLS [J].
BEHAR, L ;
MARX, R ;
SADOT, E ;
BARG, J ;
GINZBURG, I .
INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 1995, 13 (02) :113-127
[9]   Tau filaments from human brain and from in vitro assembly of recombinant protein show cross-β structure [J].
Berriman, J ;
Serpell, LC ;
Oberg, KA ;
Fink, AL ;
Goedert, M ;
Crowther, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (15) :9034-9038
[10]   Minor groove-binding architectural proteins: Structure, function, and DNA recognition [J].
Bewley, CA ;
Gronenborn, AM ;
Clore, GM .
ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE, 1998, 27 :105-131