Comprehensive review of mechanisms of pathogenesis involved in Alzheimer’s disease and potential therapeutic strategies

Sharma, Piyoosh; Srivastava, Pavan; Seth, Ankit; Tripathi, Prem Prakash; Banerjee, Anupam G.; Shrivastava, Sushant K.

doi:10.1016/j.pneurobio.2018.12.006

Cited by 262 publications

(219 citation statements)

References 551 publications

Supporting

Mentioning

206

Contrasting

Unclassified

Order By: Relevance

“…When the predicted results were further evaluated, BChE-one of the key targets related to the "response to xenobiotic stimulus" pathway-was picked for further validation. As a promising druggable target for AD, BChE activity is significantly elevated in later stages of AD [59][60][61]. Our study indicates that BChE may be a shared target for both AD and hypertension (Table 1).…”

Section: Discussionmentioning

confidence: 62%

A Network-Based Approach to Explore the Mechanisms of Uncaria Alkaloids in Treating Hypertension and Alleviating Alzheimer’s Disease

Zhang

et al. 2020

IJMS

View full text Add to dashboard Cite

Uncaria alkaloids are the major bioactive chemicals found in the Uncaria genus, which have a long history of clinical application in treating cardiovascular and mental diseases in traditional Chinese medicine (TCM). However, there are gaps in understanding the multiple targets, pathways, and biological activities of Uncaria alkaloids. By constructing the interactions among drug-targets-diseases, network pharmacology provides a systemic methodology and a novel perspective to present the intricate connections among drugs, potential targets, and related pathways. It is a valuable tool for studying TCM drugs with multiple indications, and how these multi-indication drugs are affected by complex interactions in the biological system. To better understand the mechanisms and targets of Uncaria alkaloids, we built an integrated analytical platform based on network pharmacology, including target prediction, protein–protein interaction (PPI) network, topology analysis, gene enrichment analysis, and molecular docking. Using this platform, we revealed the underlying mechanisms of Uncaria alkaloids’ anti-hypertensive effects and explored the possible application of Uncaria alkaloids in preventing Alzheimer’s disease. These results were further evaluated and refined using biological experiments. Our study provides a novel strategy for understanding the holistic pharmacology of TCM, as well as for exploring the multi-indication properties of TCM beyond its traditional applications.

show abstract

Section: Discussionmentioning

confidence: 62%

A Network-Based Approach to Explore the Mechanisms of Uncaria Alkaloids in Treating Hypertension and Alleviating Alzheimer’s Disease

Zhang

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Classic single-target chemical probes include: Acetylcholinesterase (AChase) (i.e. galantamine from galantus sp), NMDA receptors (memantine), oxidative stress (polyphenols: reseveratrol, catequins, antocianidins, etc), modulators of neuronal Acetylcholine receptors (nAChR, quinolizidinc alkaloids), or molecules that can interfere with the main event involved in the pathogenesis of disease, the amyloid b-peptide (bA) (Sala Frigerio and De Strooper, 2016;Cummings et al, 2017;Sharma et al, 2018). Moreover, during the last 15 years, no new drugs have been approved by the FDA for AD (Casey et al, 2010;Mullard, 2012;Becker et al, 2014;Cummings et al, 2017).…”

Section: Main Mechanisms Involved In Alzheimer's Disease: Target To Dmentioning

confidence: 99%

Exploring the Multi–Target Neuroprotective Chemical Space of Benzofuran Scaffolds: A New Strategy in Drug Development for Alzheimer’s Disease

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Firstly, there are several biologically plausible mechanisms by which the study drugs could have led to or contributed to neuropathological processes common t o b o t h P a r k i n s o n ' s d i s e a s e a n d a n d t o o t h e r neurodegenerative diseases (Figure 1). The inhibition of VEGF is known to lead to a reduction in synaptic function and plasticity, leading to impaired neuron signalling (Sharma et al, 2019). Furthermore, inhibition of VEGF can lead to a reduction in Bcl-2 gene expression and increase in the protein caspase-3, with both these two effects leading to increased cell death (Sanchez et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Intravitreal Anti-VEGF Drugs and Signals of Dementia and Parkinson-Like Events: Analysis of the VigiBase Database of Spontaneous Reports

et al. 2020

View full text Add to dashboard Cite

Introduction: Since vascular endothelial growth factor (VEGF) regulates several aspects of the central nervous system, particularly in dopaminergic neurons, VEGF inhibitors may be linked to Parkinson-like events and dementia, or variants of these diseases. Two recent case reports have found a potential link between intravitreal anti-VEGF use and Parkinson's disease (PD) and dementia. Aim: To evaluate disproportionality in a large spontaneous reporting database concerning intravitreal anti-VEGF drugs and PD or dementia, and related conditions. Methods: Using VigiBase, individual case safety reports (ICSRs) attributed to intravitreal ranibizumab, aflibercept, pegaptanib, and bevacizumab were identified from 2010 to 2016. Within Standardised Narrow Medical Dictionary for Regulatory Activities (MedDRA ®) Queries (SMQs) for "Parkinson-like events" and "Dementia," suspected events were identified using preferred terms (PTs). The Proportional Reporting Ratio (PRR) was estimated with the lower 95% confidence intervals (CIs) for all drug-event pairs with ≥3 suspected events. The vigiGrade completeness score was reported for the ICSRs. The analyses were repeated, including only persons aged 65 and over. Results: Out of 18.9 million ICSRs, 7,945 (0.004%) concerned intravitreal anti-VEGF drugs. Of these, 27 (0.34%) were identified concerning the SMQs "Dementia" (N = 17, 62.96%) and "Parkinson-like events" (N = 10, 37.94%) in persons of all ages. Among persons age 65 and over, 4,758 (59.88% of relevant ICSRs) ICSRs were identified for anti-VEGF drugs. When restricting disproportionality analysis to persons aged 65 and over, no disproportionality was seen for any of the drug-event pairs at the level of SMQ. However, on analysing disproportionality by PT, a potential signal emerged for intravitreal ranibizumab and Parkinson's disease [N = 6 ICSRs; PRR: 3.05 (95% CI: 1.36-6.81)]. In general, the vigiGrade completeness score was low for all the ICSRs of interest, as no ICSR had a score >0.8.

show abstract

Comprehensive review of mechanisms of pathogenesis involved in Alzheimer’s disease and potential therapeutic strategies

Cited by 262 publications

References 551 publications

A Network-Based Approach to Explore the Mechanisms of Uncaria Alkaloids in Treating Hypertension and Alleviating Alzheimer’s Disease

A Network-Based Approach to Explore the Mechanisms of Uncaria Alkaloids in Treating Hypertension and Alleviating Alzheimer’s Disease

Exploring the Multi–Target Neuroprotective Chemical Space of Benzofuran Scaffolds: A New Strategy in Drug Development for Alzheimer’s Disease

Intravitreal Anti-VEGF Drugs and Signals of Dementia and Parkinson-Like Events: Analysis of the VigiBase Database of Spontaneous Reports

Contact Info

Product

Resources

About