Is Aducanumab for LMICs? Promises and Challenges

Gunawardena, Illangage P. C.; Retinasamy, Thaarvena; Shaikh, Mohd Farooq

doi:10.3390/brainsci11111547

Cited by 5 publications

(5 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent research results have contributed to increasing the chemical diversity of 5-HT 6 R ligands. Apart from the structures of quinoline-2,4-diones (6) [34] and asenapine (7) [35] described in 2008-2009, the last five years have also provided non-indole and non-sulfonic derivatives of triazine (8, 9) [36][37][38][39], hydantoin (10) [40,41], imidazopyridine (11) [42], as well as non-basic 5-HT 6 R ligands (12,13) [43,44], which also showed procognitive activity in animal models (8)(9)(10), promising for potential AD therapies (Figure 1b).…”

Section: Chemical Variety Of 5-ht6r Ligandsmentioning

confidence: 99%

“…Moreover, the approval was mainly based on the ability of aducanumab to remove β-amyloid (Aβ) plague, whereas it has not yet been proved that Aβ clearance is correlated with cognition impairment. Finally, the cost of the treatment and the safety profile were also problematic issues [ 10 ]. In this light, searching for novel small chemical entities acting via non-standard protein targets is highly urgent to deal with this still unmet clinical need.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Multitargeting the Action of 5-HT6 Serotonin Receptor Ligands by Additional Modulation of Kinases in the Search for a New Therapy for Alzheimer’s Disease: Can It Work from a Molecular Point of View?

Czarnota-Łydka

Kucwaj-Brysz

Pyka

et al. 2022

IJMS

View full text Add to dashboard Cite

In view of the unsatisfactory treatment of cognitive disorders, in particular Alzheimer’s disease (AD), the aim of this review was to perform a computer-aided analysis of the state of the art that will help in the search for innovative polypharmacology-based therapeutic approaches to fight against AD. Apart from 20-year unrenewed cholinesterase- or NMDA-based AD therapy, the hope of effectively treating Alzheimer’s disease has been placed on serotonin 5-HT6 receptor (5-HT6R), due to its proven, both for agonists and antagonists, beneficial procognitive effects in animal models; however, research into this treatment has so far not been successfully translated to human patients. Recent lines of evidence strongly emphasize the role of kinases, in particular microtubule affinity-regulating kinase 4 (MARK4), Rho-associated coiled-coil-containing protein kinase I/II (ROCKI/II) and cyclin-dependent kinase 5 (CDK5) in the etiology of AD, pointing to the therapeutic potential of their inhibitors not only against the symptoms, but also the causes of this disease. Thus, finding a drug that acts simultaneously on both 5-HT6R and one of those kinases will provide a potential breakthrough in AD treatment. The pharmacophore- and docking-based comprehensive literature analysis performed herein serves to answer the question of whether the design of these kind of dual agents is possible, and the conclusions turned out to be highly promising.

show abstract

Section: Chemical Variety Of 5-ht6r Ligandsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multitargeting the Action of 5-HT6 Serotonin Receptor Ligands by Additional Modulation of Kinases in the Search for a New Therapy for Alzheimer’s Disease: Can It Work from a Molecular Point of View?

Czarnota-Łydka

Kucwaj-Brysz

Pyka

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…At least 60-70% of cases of dementia are caused by AD. Research suggests that AD appears to affect women more frequently than men [6,7]. However, the reason for this fact is not known.…”

Section: Introductionmentioning

confidence: 99%

Innate and adaptive glial cell responses in Alzheimer’s disease

Singh

2023

Explor Neuroprot Ther

View full text Add to dashboard Cite

Alzheimer’s disease (AD), which affects around twenty-seven million people globally, is an aging-related neurodegenerative condition characterized by the extracellular deposition of misfolded amyloid-β (Aβ) peptides and the intracellular production of neurofibrillary tangles (NFTs) AD results from the death of certain groups of neurons in the brain while appearing to have no impact on neighboring neurons. It is progressive and incurable. Therefore, the pathophysiology of afflicted populations and the development of intervention measures to stop neuronal cell death have been the main areas of attention for delineating therapeutic options. Proinflammatory cytokines are responsible for the stimulation of inflammatory responses and are mostly generated by activated macrophages in the brain. This review discusses how glial cells and innate and adaptive immune responses have a critical role in AD. It also provides information about microglial activation through the cluster of differentiation 40 (CD40) ligation and CD40L. CD40L ligation of microglial CD40 results in a large increase in tumor necrosis factor-α (TNF-α) production. Cultured cortical neuronal injury is caused when microglia are activated by CD40 ligation in the presence of interferon-γ (IFN-γ). This injury is significantly reduced by blocking the CD40 pathway or neutralising TNF-α. The management of AD would require integrating all available information about the innate and adaptive immune response affecting AD-related neuronal death.

show abstract

“…However, the cost of this drug is high, and the European Medicines Agency has not approved it due to controversies regarding its effectiveness in improving clinical outcomes and safety. Therefore, there is still much work to be done to effectively treat AD [4,5].…”

Section: Introductionmentioning

confidence: 99%

Sideritis scardica Extracts Demonstrate Neuroprotective Activity against Aβ25–35 Toxicity

Ververis

Ioannou

Kyriakou

et al. 2023

Plants

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is the most prevalent neurodegenerative condition, primarily affecting seniors. Despite the significant time and money spent over the past few decades, no therapy has been developed yet. In recent years, the research has focused on ameliorating the cytotoxic amyloid beta (Aβ) peptide aggregates and the increased elevated oxidative stress, two interconnected main AD hallmarks. Medicinal plants constitute a large pool for identifying bioactive compounds or mixtures with a therapeutic effect. Sideritis scardica (SS) has been previously characterized as neuroprotective toward AD. We investigated this ability of SS by generating eight distinct solvent fractions, which were chemically characterized and assessed for their antioxidant and neuroprotective potential. The majority of the fractions were rich in phenolics and flavonoids, and all except one showed significant antioxidant activity. Additionally, four SS extracts partly rescued the viability in Aβ25–35-treated SH-SY5Y human neuroblastoma cells, with the initial aqueous extract being the most potent and demonstrating similar activity in retinoic-acid-differentiated cells as well. These extracts were rich in neuroprotective substances, such as apigenin, myricetin-3-galactoside, and ellagic acid. Our findings indicate that specific SS mixtures can benefit the pharmaceutical industry to develop herbal drugs and functional food products that may alleviate AD.

show abstract

Is Aducanumab for LMICs? Promises and Challenges

Cited by 5 publications

References 54 publications

Multitargeting the Action of 5-HT6 Serotonin Receptor Ligands by Additional Modulation of Kinases in the Search for a New Therapy for Alzheimer’s Disease: Can It Work from a Molecular Point of View?

Multitargeting the Action of 5-HT6 Serotonin Receptor Ligands by Additional Modulation of Kinases in the Search for a New Therapy for Alzheimer’s Disease: Can It Work from a Molecular Point of View?

Innate and adaptive glial cell responses in Alzheimer’s disease

Sideritis scardica Extracts Demonstrate Neuroprotective Activity against Aβ25–35 Toxicity

Contact Info

Product

Resources

About