The Structure and Function of α, β and γ-Secretase as Therapeutic Target Enzymes in the Development of Alzheimer's Disease: A Review

被引:18
作者
Ahmad, Syed S. [1 ]
Khan, Shahzad [2 ]
Kamal, Mohammad A. [3 ,4 ,5 ]
Wasi, Umam [6 ]
机构
[1] Integral Univ, Fac Engn, Dept Bioengn, Lucknow, Uttar Pradesh, India
[2] Wuhan Univ, Sch Med, Wuhan, Hubei, Peoples R China
[3] King Abdulaziz Univ, King Fahd Med Res Ctr, POB 80216, Jeddah 21589, Saudi Arabia
[4] Enzymo, 7 Peterlee Pl, Hebersham, NSW 2770, Australia
[5] Novel Global Community Educ Fdn, Sydney, NSW, Australia
[6] Integral Univ, Fac Sci, Dept Biosci, Lucknow, Uttar Pradesh, India
关键词
Alzheimer's disease; secretase activity; nanotechnology; BBB; APP; treatment; AMYLOID PRECURSOR PROTEIN; MISSENSE MUTATIONS; DIABETES-MELLITUS; MOLECULAR DOCKING; SIGNALING PATHWAY; HYPOTHESIS; NANOPARTICLES; GENE; CLEAVAGE; PEPTIDE;
D O I
10.2174/1871527318666191011145941
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
Alzheimer's disease is a progressive neurodegenerative disorder that affects the central nervous system. There are several factors that cause AD, like, intracellular hyperphosphorylated Tau tangles, collection of extracellular Amyloid-beta 42 and generation of reactive oxygen species due to mitochondria) dysfunction. This review analyses the most active target of AD and both types of AD-like early-onset AD and late-onset AD. BACE1 is a beta-secretase involved in the cleavage of amyloid precursor protein and the pathogenesis of Alzheimer's disease. The presenilin proteins play a critical role in the pathogenesis of Alzheimer malady by intervening the intramembranous cleavage of amyloid precursor protein and the generation of amyloid beta. The two homologous proteins PS1 and PS2 speak to the reactant subunits of particular gamma-secretase edifices that intercede an assortment of cellular processes. Natural products are common molecular platforms in drug development in AD. Many natural products are being tested in various animal model systems for their role as a potential therapeutic target in AD. Presently, there are a few theories clarifying the early mechanisms of AD pathogenesis. Recently, research advancements in the field of nanotechnology, which utilize macromolecular strategies to make drugs in nanoscale measurements, offer nanotechnology-based diagnostic tools and drug carriers which are highly sensitive for effective drug targeting in the treatment of Alzheimer's disease.
引用
收藏
页码:657 / 667
页数:11
相关论文
共 106 条
[1]
Nanotechnology Based Theranostic Approaches in Alzheimer's Disease Management: Current Status and Future Perspective [J].
Ahmad, Javed ;
Akhter, Sohail ;
Rizwanullah, Md. ;
Khan, Mohammad Ahmed ;
Pigeon, Lucie ;
Addo, Richard T. ;
Greig, Nigel H. ;
Midoux, Patrick ;
Pichon, Chantal ;
Kamal, Mohammad Amjad .
CURRENT ALZHEIMER RESEARCH, 2017, 14 (11) :1164-1181
[2]
Screening and Elucidation of Selected Natural Compounds for Anti-Alzheimer's Potential Targeting BACE-1 Enzyme: A Case Computational Study [J].
Ahmad, Syed Sayeed ;
Akhtar, Salman ;
Rizvi, Syed Mohd. Danish ;
Kamal, Mohammad A. ;
Sayeed, Usman ;
Khan, Mohd. Kalim A. ;
Siddiqui, Mohd. Haris ;
Arif, Jamal M. .
CURRENT COMPUTER-AIDED DRUG DESIGN, 2017, 13 (04) :311-318
[3]
Multiple Targets for the Management of Alzheimer's Disease [J].
Ahmad, Syed Sayeed ;
Akhtar, Salman ;
Jamal, Qazi Mohammad Sajid ;
Rizvi, Syed Mohd. Danish ;
Kamal, Mohammad A. ;
Khan, M. Kalim A. ;
Siddiqui, Mohd. Haris .
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS, 2016, 15 (10) :1279-1289
[4]
Diabetes mellitus and Alzheimer's disease: shared pathology and treatment? [J].
Akter, Kawser ;
Lanza, Emily A. ;
Martin, Stephen A. ;
Myronyuk, Natalie ;
Rua, Melanie ;
Raffa, Robert B. .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2011, 71 (03) :365-376
[5]
2018 Alzheimer's disease facts and figures [J].
不详 .
ALZHEIMERS & DEMENTIA, 2018, 14 (03) :367-425
[6]
Ameliorative Effect of Trans-Sinapic Acid and its Protective Role in Cerebral Hypoxia in Aluminium Chloride Induced Dementia of Alzheimer's Type [J].
Bais, Souravh ;
Kumari, Renu ;
Prashar, Yash .
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS, 2018, 17 (02) :144-154
[7]
The blood-brain barrier: an overview - Structure, regulation, and clinical implications [J].
Ballabh, P ;
Braun, A ;
Nedergaard, M .
NEUROBIOLOGY OF DISEASE, 2004, 16 (01) :1-13
[8]
Role of the APP non-amyloidogenic signaling pathway and targeting α-secretase as an alternative drug target for treatment of Alzheimer's disease [J].
Bandyopadhyay, S. ;
Goldstein, L. E. ;
Lahiri, D. K. ;
Rogers, J. T. .
CURRENT MEDICINAL CHEMISTRY, 2007, 14 (27) :2848-2864
[9]
Signs and symptoms preceding the diagnosis of Alzheimer's disease: a systematic scoping review of literature from 1937 to 2016 [J].
Bature, Fidelia ;
Guinn, Barbara-ann ;
Pang, Dong ;
Pappas, Yannis .
BMJ OPEN, 2017, 7 (08)
[10]
Protective Effect of Kaempferol on the Transgenic Drosophila Model of Alzheimer's Disease [J].
Beg, Tanveer ;
Jyoti, Smita ;
Naz, Falaq ;
Rahul ;
Ali, Fahad ;
Ali, Syed Kashif ;
Reyad, Ahmed Mohamed ;
Siddique, Yasir Hasan .
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS, 2018, 17 (06) :421-429