Overlapped Metabolic and Therapeutic Links between Alzheimer and Diabetes

被引:71
作者
Ahmad, Waqar [1 ]
机构
[1] Univ Queensland, Sch Biol Sci, Paul R Ebert Lab, Brisbane, Qld 4072, Australia
关键词
Alzheimer's disease; Diabetes; Pathophysiology; Impaired metabolism; Therapies; C; elegans; GLYCATION END-PRODUCTS; AMYLOID-BETA-PEPTIDE; MILD COGNITIVE IMPAIRMENT; INSULIN-RECEPTOR SUBSTRATE-1; CEREBRAL GLUCOSE-METABOLISM; GLYCOGEN-SYNTHASE KINASE-3; INDUCED OXIDATIVE STRESS; GROWTH-FACTOR EXPRESSION; CENTRAL-NERVOUS-SYSTEM; MOUSE MODEL;
D O I
10.1007/s12035-012-8352-z
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Alzheimer's disease (AD) and diabetes are among the most common diseases associated with ageing. The pathology of AD is strongly associated with accumulated misfolding proteins that results in neuronal dysfunction within the brain. Diabetes, on the contrary, is characterised by altered insulin signaling that results in reduced glucose uptake, metabolic suppression of energy consuming cells and conversion of glucose to fat in the liver. Despite distinguishing features, these diseases share common elements and may in fact be viewed as fundamentally similar disorders that differ in magnitude of specific traits, primarily affected tissues and time of onset. In this review, we outline the fundamental basis of each of the two diseases and highlight similarities in their pathophysiology. Further ahead we will discuss these features in relation to the development of drugs to treat these two diseases, particularly AD, for which the development of therapeutic chemicals has proven to be particularly difficult. We conclude with comments on efforts to develop a simple organism, Caenorhabditis elegans, as a genetic model to be used to study the systems biology of diabetes and AD.
引用
收藏
页码:399 / 424
页数:26
相关论文
共 334 条
[11]   Dissecting the role of the 3-phosphoinositide-dependent protein kinase-1 (PDK1) signalling pathways [J].
Bayascas, Jose R. .
CELL CYCLE, 2008, 7 (19) :2978-2982
[12]   Activation of the amyloid cascade in apolipoprotein E4 transgenic mice induces lysosomal activation and neurodegeneration resulting in marked cognitive deficits [J].
Belinson, Haim ;
Lev, Dimitri ;
Masliah, Eliezer ;
Michaelson, Daniel M. .
JOURNAL OF NEUROSCIENCE, 2008, 28 (18) :4690-4701
[13]   PIOGLITAZONE IMPROVED COGNITION IN A PILOT STUDY ON PATIENTS WITH ALZHEIMER'S DISEASE AND MILD COGNITIVE IMPAIRMENT WITH DIABETES MELLITUS [J].
Bellelli, Giuseppe ;
Morghen, Sara ;
Torpilliesi, Tiziana ;
Trabucchi, Marco .
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, 2009, 57 (01) :178-179
[14]   Elk-1 a transcription factor with multiple facets in the brain [J].
Besnard, Antoine ;
Galan-Rodriguez, Beatriz ;
Vanhoutte, Peter ;
Caboche, Jocelyne .
FRONTIERS IN NEUROSCIENCE, 2011, 5
[15]   ACAT inhibition and amyloid beta reduction [J].
Bhattacharyya, Raja ;
Kovacs, Dora M. .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2010, 1801 (08) :960-965
[16]   Ageing and diabetes: implications for brain function [J].
Biessels, GJ ;
van der Heide, LP ;
Kamal, A ;
Bleys, RLAW ;
Gispen, WH .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2002, 441 (1-2) :1-14
[17]   Crossing the barrier:: oxysterols as cholesterol transporters and metabolic modulators in the brain [J].
Bjorkhem, I. .
JOURNAL OF INTERNAL MEDICINE, 2006, 260 (06) :493-508
[18]   Oxidative stress in Alzheimer disease: A possibility for prevention [J].
Bonda, David J. ;
Wang, Xinglong ;
Perry, George ;
Nunomura, Akihiko ;
Tabaton, Massimo ;
Zhu, Xiongwei ;
Smith, Mark A. .
NEUROPHARMACOLOGY, 2010, 59 (4-5) :290-294
[19]   Insulin Resistance, Hyperglycemia, and Atherosclerosis [J].
Bornfeldt, Karin E. ;
Tabas, Ira .
CELL METABOLISM, 2011, 14 (05) :575-585
[20]   Possible implications of insulin resistance and glucose metabolism in Alzheimer's disease pathogenesis [J].
Bosco, Domenico ;
Fava, Antonietta ;
Plastino, Massimiliano ;
Montalcini, Tiziana ;
Pujia, Arturo .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2011, 15 (09) :1807-1821