Current Therapeutic Targets for Alzheimer's Disease

Chaudhary, Amit; Maurya, Pramod Kumar; Yadav, Birendra Singh; Singh, Swati; Mani, Ashutosh

doi:10.7150/jbm.26783

Cited by 28 publications

(24 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the combination therapy of donepezil with cilostazol showed positive effects on patients with mild or moderate-to-severe Alzheimer’s patients [ 91 , 92 ]. To conclude, there are many biological targets and signalling pathways involved in AD pathology [ 93 , 94 ]. However, the complex interactions between them is unclear.…”

Section: Ad-related Targetsmentioning

confidence: 99%

Perspectives for New and More Efficient Multifunctional Ligands for Alzheimer′s Disease Therapy

Zagórska

Jaromin

2020

Molecules

View full text Add to dashboard Cite

Despite tremendous research efforts at every level, globally, there is still a lack of effective drugs for the treatment of Alzheimer′s disease (AD). The biochemical mechanisms of this devastating neurodegenerative disease are not yet clearly understood. This review analyses the relevance of multiple ligands in drug discovery for AD as a versatile toolbox for a polypharmacological approach to AD. Herein, we highlight major targets associated with AD, ranging from acetylcholine esterase (AChE), beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1), glycogen synthase kinase 3 beta (GSK-3β), N-methyl-d-aspartate (NMDA) receptor, monoamine oxidases (MAOs), metal ions in the brain, 5-hydroxytryptamine (5-HT) receptors, the third subtype of histamine receptor (H3 receptor), to phosphodiesterases (PDEs), along with a summary of their respective relationship to the disease network. In addition, a multitarget strategy for AD is presented, based on reported milestones in this area and the recent progress that has been achieved with multitargeted-directed ligands (MTDLs). Finally, the latest publications referencing the enlarged panel of new biological targets for AD related to the microglia are highlighted. However, the question of how to find meaningful combinations of targets for an MTDLs approach remains unanswered.

show abstract

Section: Ad-related Targetsmentioning

confidence: 99%

Perspectives for New and More Efficient Multifunctional Ligands for Alzheimer′s Disease Therapy

Zagórska

Jaromin

2020

Molecules

View full text Add to dashboard Cite

show abstract

“…When APPs are processed by β and γ-secretase form Aβ40 and Aβ42 peptides, which then undergo aggregation and oligomer formation and eventually cause formation of amyloids plaques [71,72]. About 95% cases of AD are sporadic, and older age, hypertension, diabetes, heart disease, and apolipoprotein E (ApoE) 4 allele polymorphism are considered as some of the key factors involved in the development of the disease [73]. Currently, there are several attractive targets for anti-AD drug design.…”

Section: Drug Design and Discovery Targeting Nddmentioning

confidence: 99%

“…Currently, there are several attractive targets for anti-AD drug design. Some of these targets already have FDA-approved inhibitors such as AChE (donepezil, rivastigmine, and galantamine [73]) and NMDA receptor (memantine [74]). Other targets for the design of effective and potent inhibitors are still under study.…”

Section: Drug Design and Discovery Targeting Nddmentioning

confidence: 99%

“…Other targets for the design of effective and potent inhibitors are still under study. These include βand γ-secretase [75,76]; BChE (neuritic plaques and neurofibrillary tangles [77]); calcitonin gene-regulated peptide (Neurotransmitter) [78]; phosphodiesterase (hydrolysis of cGMP) [73]; mAchR (hyperphosphorylation of Tau protein) [79]; dopamine 2 receptor (Aβ plaques) [80]; GABA-A receptor [81]; serotonin 5-HT6 receptor (improving cognition dysfunction, synaptic plasticity) [82]; among others. Here we review some of the most studied targets and how the design of bioactive compounds was done.…”

Section: Drug Design and Discovery Targeting Nddmentioning

confidence: 99%

See 1 more Smart Citation

Theoretical and Experimental Approaches Aimed at Drug Design Targeting Neurodegenerative Diseases

et al. 2019

View full text Add to dashboard Cite

In recent years, green chemistry has been strengthening, showing how basic and applied sciences advance globally, protecting the environment and human health. A clear example of this evolution is the synergy that now exists between theoretical and computational methods to design new drugs in the most efficient possible way, using the minimum of reagents and obtaining the maximum yield. The development of compounds with potential therapeutic activity against multiple targets associated with neurodegenerative diseases/disorders (NDD) such as Alzheimer’s disease is a hot topic in medical chemistry, where different scientists from various disciplines collaborate to find safe, active, and effective drugs. NDD are a public health problem, affecting mainly the population over 60 years old. To generate significant progress in the pharmacological treatment of NDD, it is necessary to employ different experimental strategies of green chemistry, medical chemistry, and molecular biology, coupled with computational and theoretical approaches such as molecular simulations and chemoinformatics, all framed in the rational drug design targeting NDD. Here, we review how green chemistry and computational approaches have been used to develop new compounds with the potential application against NDD, as well as the challenges and new directions of the drug development multidisciplinary process.

show abstract

“…The Kelch-like ECH-associated protein 1 (Keap1)/Nrf2/ARE pathway is one of the most potent defensive systems against oxidative stress [20]. In addition, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), NADPH oxidase (NOX), lipoxygenase (LOX), c-Jun N-terminal kinase 3 (JNK-3), protein tyrosine phosphatase 1B (PTP1B), phosphodiesterase type 5 (PDE5), NADPH oxidase, sodium-glucose cotransporter (SGLT)1, SGLT2, and DJ-1 have been associated with the expression of antiinflammatory mediators, neuroprotection, and ROS regulation and therefore represent promising AD targets [21][22][23][24][25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Identification of New Targets and the Virtual Screening of Lignans against Alzheimer’s Disease

Maia

Rodrigues

Sousa

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is characterized by the progressive disturbance in cognition and affects approximately 36 million people, worldwide. However, the drugs used to treat this disease are only moderately effective and do not alter the course of the neurodegenerative process. This is because the pathogenesis of AD is mainly associated with oxidative stress, and current drugs only target two enzymes involved in neurotransmission. Therefore, the present study sought to identify potential multitarget compounds for enzymes that are directly or indirectly involved in the oxidative pathway, with minimal side effects, for AD treatment. A set of 159 lignans were submitted to studies of QSAR and molecular docking. A combined analysis was performed, based on ligand and structure, followed by the prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. The results showed that the combined analysis was able to select 139 potentially active and multitarget lignans targeting two or more enzymes, among them are c-Jun N-terminal kinase 3 (JNK-3), protein tyrosine phosphatase 1B (PTP1B), nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), NADPH quinone oxidoreductase 1 (NQO1), phosphodiesterase 5 (PDE5), nuclear factor erythroid 2-related factor 2 (Nrf2), cycloxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). The authors conclude that compounds (06) austrobailignan 6, (11) anolignan c, (19) 7-epi-virolin, (64) 6-[(2R,3R,4R,5R)-3,4-dimethyl-5-(3,4,5-trimethoxyphenyl)oxolan-2-yl]-4-methoxy-1,3-benzodioxole, (116) ococymosin, and (135) mappiodoinin b have probabilities that confer neuroprotection and antioxidant activity and represent potential alternative AD treatment drugs or prototypes for the development of new drugs with anti-AD properties.

show abstract

Current Therapeutic Targets for Alzheimer's Disease

Cited by 28 publications

References 5 publications

Perspectives for New and More Efficient Multifunctional Ligands for Alzheimer′s Disease Therapy

Perspectives for New and More Efficient Multifunctional Ligands for Alzheimer′s Disease Therapy

Theoretical and Experimental Approaches Aimed at Drug Design Targeting Neurodegenerative Diseases

Identification of New Targets and the Virtual Screening of Lignans against Alzheimer’s Disease

Contact Info

Product

Resources

About