Molecular Pathogenesis and Interventional Strategies for Alzheimer's Disease: Promises and Pitfalls

被引:23
作者
Bhute, Shashikala [1 ]
Sarmah, Deepaneeta [1 ]
Datta, Aishika [1 ]
Rane, Pallavi [1 ]
Shard, Amit [1 ]
Goswami, Avirag [2 ]
Borah, Anupom [3 ]
Kalia, Kiran [1 ]
Dave, Kunjan R. [4 ]
Bhattacharya, Pallab [1 ]
机构
[1] Natl Inst Pharmaceut Educ & Res NIPER, Dept Pharmacol & Toxicol, Gandhinagar 382355, Gujarat, India
[2] Albert Einstein Med Ctr, Dept Neurol, Philadelphia, PA 19141 USA
[3] Assam Univ, Dept Life Sci & Bioinformat, Silchar 788011, Assam, India
[4] Univ Miami, Dept Neurol, Miller Sch Med, Miami, FL 33136 USA
关键词
proteoglycans; sirtuins; apolipoprotein; immune system; RanBP9; PrPC; SECRETASE-ACTIVATING PROTEIN; HEPARAN-SULFATE PROTEOGLYCANS; DENSITY-LIPOPROTEIN RECEPTOR; TRANSGENIC MOUSE MODEL; CELLULAR PRION PROTEIN; RANDOMIZED-TRIAL; APOLIPOPROTEIN-E; NEURODEGENERATIVE DISEASES; THERAPEUTIC TARGET; AMYLOID PATHOLOGY;
D O I
10.1021/acsptsci.9b00104
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Alzheimer's disease (AD) is a debilitating disorder characterized by age-related dementia, which has no effective treatment to date. beta-Amyloid depositions and hyperphosphorylated tau proteins are the main pathological hallmarks, along with oxidative stress, N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity, and low levels of acetylcholine. Current pharmacotherapy for AD only provides symptomatic relief and limited improvement in cognitive functions. Many molecules have been explored that show promising outcomes in AD therapy and can regulate cellular survival through different pathways. To have a vivid approach to strategize the treatment regimen, AD physiopathology should be better explained considering diverse etiological factors in conjunction with biochemical disturbances. This Review attempts to discuss different disease modification approaches and address the novel therapeutic targets of AD that might pave the way for new drug discovery using the well-defined targets for therapy of the disease.
引用
收藏
页码:472 / 488
页数:17
相关论文
共 189 条
[71]   MicroRNA Let-7f-5p Promotes Bone Marrow Mesenchymal Stem Cells Survival by Targeting Caspase-3 in Alzheimer Disease Model [J].
Han, Linlin ;
Zhou, Yan ;
Zhang, Ruiyi ;
Wu, Kaimin ;
Lu, Yanhui ;
Li, Yanfei ;
Duan, Ranran ;
Yao, Yaobing ;
Zhu, Dengna ;
Jia, Yanjie .
FRONTIERS IN NEUROSCIENCE, 2018, 12
[72]   Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease [J].
He, Gen ;
Luo, Wenjie ;
Li, Peng ;
Remmers, Christine ;
Netzer, William J. ;
Hendrick, Joseph ;
Bettayeb, Karima ;
Flajolet, Marc ;
Gorelick, Fred ;
Wennogle, Lawrence P. ;
Greengard, Paul .
NATURE, 2010, 467 (7311) :95-U129
[73]   Deletion of tumor necrosis factor death receptor inhibits amyloid β generation and prevents learning and memory deficits in Alzheimer's mice [J].
He, Ping ;
Zhong, Zhenyu ;
Lindholm, Kristina ;
Berning, Lilian ;
Lee, Wendy ;
Lemere, Cynthia ;
Staufenbiel, Matthias ;
Li, Rena ;
Shen, Yong .
JOURNAL OF CELL BIOLOGY, 2007, 178 (05) :829-841
[74]   Inflammatory Eicosanoids Increase Amyloid Precursor Protein Expression via Activation of Multiple Neuronal Receptors [J].
Herbst-Robinson, Katie J. ;
Liu, Li ;
James, Michael ;
Yao, Yuemang ;
Xie, Sharon X. ;
Brunden, Kurt R. .
SCIENTIFIC REPORTS, 2015, 5
[75]   Sirtuin deacetylases in neurodegenerative diseases of aging [J].
Herskovits, Adrianna Z. ;
Guarente, Leonard .
CELL RESEARCH, 2013, 23 (06) :746-758
[76]   Reelin, lipoprotein receptors and synaptic plasticity [J].
Herz, Joachim ;
Chen, Ying .
NATURE REVIEWS NEUROSCIENCE, 2006, 7 (11) :850-859
[77]   Microglial dysfunction and defective β-amyloid clearance pathways in aging Alzheimer's disease mice [J].
Hickman, Suzanne E. ;
Allison, Elizabeth K. ;
El Khoury, Joseph .
JOURNAL OF NEUROSCIENCE, 2008, 28 (33) :8354-8360
[78]   Defensive effect of microRNA-200b/c against amyloid-beta peptide-induced toxicity in Alzheimer's disease models [J].
Higaki, Sayuri ;
Muramatsu, Masashi ;
Matsuda, Akio ;
Matsumoto, Kenji ;
Satoh, Jun-ichi ;
Michikawa, Makoto ;
Niida, Shumpei .
PLOS ONE, 2018, 13 (05)
[79]   Mitochondrial abnormalities in Alzheimer's disease [J].
Hirai, K ;
Aliev, G ;
Nunomura, A ;
Fujioka, H ;
Russell, RL ;
Atwood, CS ;
Johnson, AB ;
Kress, Y ;
Vinters, HV ;
Tabaton, M ;
Shimohama, S ;
Cash, AD ;
Siedlak, SL ;
Harris, PLR ;
Jones, PK ;
Petersen, RB ;
Perry, G ;
Smith, MA .
JOURNAL OF NEUROSCIENCE, 2001, 21 (09) :3017-3023
[80]   Herpes simplex virus RNAi and neprilysin gene transfer vectors reduce accumulation of Alzheimer's disease-related amyloid-β peptide in vivo [J].
Hong, C-S ;
Goins, W. F. ;
Goss, J. R. ;
Burton, E. A. ;
Glorioso, J. C. .
GENE THERAPY, 2006, 13 (14) :1068-1079