Therapeutic Potential of AMP-Activated Protein Kinase in Alzheimer's Disease

被引：54

作者：

Wang, Xin ^{[1
]}

Zimmermann, Helena R. ^{[1
]}

Ma, Tao ^{[1
,2
,3
]}

机构：

[1] Wake Forest Sch Med, Dept Internal Med Gerontol & Geriatr Med, Winston Salem, NC USA

[2] Wake Forest Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC USA

[3] Wake Forest Sch Med, Dept Neurobiol & Anat, Winston Salem, NC USA

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2019年 / 68卷 / 01期

基金：

美国国家卫生研究院;

关键词：

Alzheimer's disease; AMPK; protein synthesis; signaling transduction; synaptic plasticity; SYNAPTIC PLASTICITY; AMYLOID-BETA; SUBSTRATE-SPECIFICITY; INSULIN-RESISTANCE; ANTIDIABETIC DRUGS; SIGNALING PATHWAY; ENERGY SENSOR; TAU; INHIBITION; BRAIN;

D O I：

10.3233/JAD-181043

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Currently there is no cure or effective disease-modifying therapy for Alzheimer's disease (AD), the most common form of dementia that is becoming a global threat to public health. It is important to develop novel therapeutic strategies targeting AD pathophysiology particularly synaptic failure and cognitive impairments. Recent studies revealed several molecular signaling pathways potentially linked to brain pathology and synaptic failure in AD, including AMP-activated protein kinase (AMPK), a master kinase that plays a central role in the maintenance of cellular energy homeostasis. Particularly, hyperactive AMPK via phosphorylation has been linked to AD-associated synaptic plasticity impairments, indicating suppression of AMPK activity might be beneficial for cognitive deficiency in AD. In this review, we will discuss how targeting dysregulation of AMPK signaling could be a feasible therapeutic approach for AD.

引用

页码：33 / 38

页数：6

共 53 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] Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums [J].

Arnold, Steven E. ;

Arvanitakis, Zoe ;

Macauley-Rambach, Shannon L. ;

Koenig, Aaron M. ;

Wang, Hoau-Yan ;

Ahima, Rexford S. ;

Craft, Suzanne ;

Gandy, Sam ;

Buettner, Christoph ;

Stoeckel, Luke E. ;

Holtzman, David M. ;

Nathan, David M. .

NATURE REVIEWS NEUROLOGY, 2018, 14 (03) :168-181

[3] Antidiabetic drugs restore abnormal transport of amyloid-β across the blood-brain barrier and memory impairment in db/db mice [J].

Chen, Fang ;

Dong, Rong Rong ;

Zhong, Kai Long ;

Ghosh, Arijit ;

Tang, Su Su ;

Long, Yan ;

Hu, Mei ;

Miao, Ming Xing ;

Liao, Jian Min ;

Sun, Hong Bing ;

Kong, Ling Yi ;

Hong, Hao .

NEUROPHARMACOLOGY, 2016, 101 :123-136

[4] Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription [J].

Chen, Yaomin ;

Zhou, Kun ;

Wang, Ruishan ;

Liu, Yun ;

Kwak, Young-Don ;

Ma, Tao ;

Thompson, Robert C. ;

Zhao, Yongbo ;

Smith, Layton ;

Gasparini, Laura ;

Luo, Zhijun ;

Xu, Huaxi ;

Liao, Francesca-Fang .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (10) :3907-3912

[5] Translational Control of Long-Lasting Synaptic Plasticity and Memory [J].

Costa-Mattioli, Mauro ;

Sossin, Wayne S. ;

Klann, Eric ;

Sonenberg, Nahum .

NEURON, 2009, 61 (01) :10-26

[6] INHIBITION OF GLYCOGEN-SYNTHASE KINASE-3 BY INSULIN-MEDIATED BY PROTEIN-KINASE-B [J].

CROSS, DAE ;

ALESSI, DR ;

COHEN, P ;

ANDJELKOVICH, M ;

HEMMINGS, BA .

NATURE, 1995, 378 (6559) :785-789

[7] p70S6 Kinase Phosphorylates AMPK on Serine 491 to Mediate Leptin's Effect on Food Intake [J].

Dagon, Yossi ;

Hur, Elizabeth ;

Zheng, Bin ;

Wellenstein, Kerry ;

Cantley, Lewis C. ;

Kahn, Barbara B. .

CELL METABOLISM, 2012, 16 (01) :104-112

[8] Metabolic-cognitive syndrome: A cross-talk between metabolic syndrome and Alzheimer's disease [J].

Frisardi, Vincenza ;

Solfrizzi, Vincenzo ;

Seripa, Davide ;

Capurso, Cristiano ;

Santamato, Andrea ;

Sancarlo, Daniele ;

Vendemiale, Gianluigi ;

Pilotto, Alberto ;

Panza, Francesco .

AGEING RESEARCH REVIEWS, 2010, 9 (04) :399-417

[9] Peripheral insulin-sensitizer drug metformin ameliorates neuronal insulin resistance and Alzheimer's-like changes [J].

Gupta, Amit ;

Bisht, Bharti ;

Dey, Chinmoy Sankar .

NEUROPHARMACOLOGY, 2011, 60 (06) :910-920

[10] Akt activates the mammalian target of rapamycin by regulating cellular ATP level and AMPK activity [J].

Hahn-Windgassen, A ;

Nogueira, V ;

Chen, CC ;

Skeen, JE ;

Sonenberg, N ;

Hay, N .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (37) :32081-32089

← 1 2 3 4 5 6 →