Cdk5 deregulation in the pathogenesis of Alzheimer's disease

被引：216

作者：

Cruz, JC ^{[1
]}

Tsai, LH ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Pathol, Boston, MA 02115 USA

来源：

TRENDS IN MOLECULAR MEDICINE | 2004年 / 10卷 / 09期

关键词：

D O I：

10.1016/j.molmed.2004.07.001

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：

The aberrant metabolism of tau and (beta-amyloid precursor protein (APP) has key roles in the neurodegenerative processes that contribute to the etiology of Alzheimer's disease (AD). These pathological characteristics of AD have recently been linked to the deregulation of cyclin-dependent kinase 5 (cdk5). The finding that the inducible expression of p25, which is the neurotoxic activator of cdk5, triggers progressive neurodegeneration and neurofibrillary tangle formation in mice provides compelling evidence that p25-cdk5 is one of the crucial pathways that can lead to AD pathophysiology. Furthermore, a role for cdk5 in modulating APP processing and (beta-amyloid generation is emerging. Therefore, as one of the molecular links between APP and tau, cdk5 might be a valuable target for therapeutic intervention in AD and other neurodegenerative diseases.

引用

页码：452 / 458

页数：7

共 72 条

[1] Hyperphosphorylated tan and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5 [J].

Ahlijanian, MK ;

Barrezueta, NX ;

Williams, RD ;

Jakowski, A ;

Kowsz, KP ;

McCarthy, S ;

Coskran, T ;

Carlo, A ;

Seymour, PA ;

Burkhardt, JE ;

Nelson, RB ;

McNeish, JD .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (06) :2910-2915

[2] Inhibition of tau phosphorylating protein kinase cdk5 prevents β-amyloid-induced neuronal death [J].

Alvarez, A ;

Toro, R ;

Cáceres, A ;

Maccioni, RB .

FEBS LETTERS, 1999, 459 (03) :421-426

[3] Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of β-amyloid [J].

Ando, K ;

Iijima, K ;

Elliott, JI ;

Kirino, Y ;

Suzuki, T .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (43) :40353-40361

[4] Improved reversal learning and altered fear conditioning in transgenic mice with regionally restricted p25 expression [J].

Angelo, M ;

Plattner, F ;

Irvine, EE ;

Giese, KP .

EUROPEAN JOURNAL OF NEUROSCIENCE, 2003, 18 (02) :423-431

[5] Colocalization and fluorescence resonance energy transfer between cdk5 and AT8 suggests a close association in pre-neurofibrillary tangles and neurofibrillary tangles [J].

Augustinack, JC ;

Sanders, JL ;

Tsai, LH ;

Hyman, BT .

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2002, 61 (06) :557-564

[6] Axonopathy, tau abnormalities, and dyskinesia, but no neurofibrillary tangles in p25-transgenic mice [J].

Bian, F ;

Nath, R ;

Sobocinski, G ;

Booher, RN ;

Lipinski, WJ ;

Callahan, MJ ;

Pack, A ;

Wang, KKW ;

Walker, LC .

JOURNAL OF COMPARATIVE NEUROLOGY, 2002, 446 (03) :257-266

[7] A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene (P301L) [J].

Bird, TD ;

Nochlin, D ;

Poorkaj, P ;

Cherrier, M ;

Kaye, J ;

Payami, H ;

Peskind, E ;

Lampe, TH ;

Nemens, E ;

Boyer, PJ ;

Schellenberg, GD .

BRAIN, 1999, 122 :741-756

[8] Increase of cdk5 is related to neurofibrillary pathology in progressive supranuclear palsy [J].

Borghi, R ;

Giliberto, L ;

Assini, A ;

Delacourte, A ;

Perry, G ;

Smith, MA ;

Strocchi, P ;

Zaccheo, D ;

Tabaton, M .

NEUROLOGY, 2002, 58 (04) :589-592

[9]

Bu BT, 2002, J NEUROSCI, V22, P6515

[10] Metals and neuroscience [J].

Bush, AI .

CURRENT OPINION IN CHEMICAL BIOLOGY, 2000, 4 (02) :184-191

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