Multi-Target-Directed Ligands and other Therapeutic Strategies in the Search of a Real Solution for Alzheimer’s Disease

Agis-Torres, Angel; Sollhuber, Monica; Fernandez, Maria; Sanchez-Montero, J.M.

doi:10.2174/1570159x113116660047

Cited by 234Alzheimer's disease research and treatmentsCholinesterase and Neurodegenerative DiseasesDementia and Cognitive Impairment Research

Multi-Target-Directed Ligands and other Therapeutic Strategies in the Search of a Real Solution for Alzheimer’s Disease

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Agis-Torres, Angel, Sollhuber, Monica, Fernandez, Maria, Sanchez-Montero, J.M.·2014·Current Neuropharmacology

DOI 10.2174/1570159x113116660047PMC PMC3915347

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Abstract

The lack of an adequate therapy for Alzheimer's Disease (AD) contributes greatly to the continuous growing amount of papers and reviews, reflecting the important efforts made by scientists in this field. It is well known that AD is the most common cause of dementia, and up-to-date there is no prevention therapy and no cure for the disease, which contrasts with the enormous efforts put on the task. On the other hand many aspects of AD are currently debated or even unknown. This review offers a view of the current state of knowledge about AD which includes more relevant findings and processes that take part in the disease; it also shows more relevant past, present and future research on therapeutic drugs taking into account the new paradigm "Multi-Target-Directed Ligands" (MTDLs). In our opinion, this paradigm will lead from now on the research toward the discovery of better therapeutic solutions, not only in the case of AD but also in other complex diseases. This review highlights the strategies followed by now, and focuses other emerging targets that should be taken into account for the future development of new MTDLs. Thus, the path followed in this review goes from the pathology and the processes involved in AD to the strategies to consider in on-going and future researches.

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Neurofibrillary tangles contain aggregates of tau protein in a hyperphosphorylated state.
“NTFs contain, as their first component, aggregates of the protein tau (τ) in a hyperphosphorylated state.”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [20]
In healthy neuronal cells, tau protein assembles and stabilizes microtubules and determines their binding with other cytoskeleton components.
“in healthy neuronal cells, following consecutive and reversible enzymatic processes of phosphorylation and dephosphorylation, it has the task of assembling and stabilizing microtubules and determining their binding with other components of the cytoskeleton [19,20].”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [20]
Alzheimer's disease is a complex and multifactorial disorder.
“a complex and multifactorial disorder, such as AD, must be approached with multitarget-directed ligands (MTDLs) (Agis-Torres et al., 2014).”
From Multi-target neuroprotective effects of herbal medicines for Alzheimer's disease (2022) · cites this paper as Agis-Torres et al., 2014

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“It was also found that a reduction of the acetylcholine synthesizing enzyme (choline acetyltransferase, ChAT) correlates with the grade of dementia [55].”
Background
Preliminary studies of a novel bifunctional metal chelator targeting Alzheimer's amyloidogenesis
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Molecular Hybridization as a Tool for Designing Multitarget Drug Candidates for Complex Diseases
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“The tau protein is a filamentous protein associated with microtubules; in healthy neuronal cells, following consecutive and reversible enzymatic processes of phosphorylation and dephosphorylation, it has the task of assembling and stabilizing microtubules and determining their binding with other components of the cyto…”
Background
Silibinin inhibits acetylcholinesterase activity and amyloid β peptide aggregation: a dual-target drug for the treatment of Alzheimer’s disease
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4,6-Diphenylpyrimidine Derivatives as Dual Inhibitors of Monoamine Oxidase and Acetylcholinesterase for the Treatment of Alzheimer’s Disease
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Combating Neurodegenerative Diseases with the Plant Alkaloid Berberine: Molecular Mechanisms and Therapeutic Potential
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Recent Progress in Repositioning Alzheimer'S Disease Drugs Based on a Multitarget Strategy
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Design, synthesis and biological evaluation of novel coumarin- N -benzyl pyridinium hybrids as multi-target agents for the treatment of Alzheimer's disease
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Synthesis and evaluation of 4-hydroxyl aurone derivatives as multifunctional agents for the treatment of Alzheimer’s disease
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Multi-target-directed ligands and other therapeutic strategies in the search of a real solution for Alzheimer’s disease. Curr. Neuropharmacol. 12, 2–36. doi: 10.2174/1570159X113116660047 Alzheimer’s Association
Agis-torres, A., Söllhuber, M. M., Fern, M., & Sanchez-montero, J. M. (2014)
Multi-Target-Directed Ligands in Alzheimer’s Disease Therapy
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Multi-Target-Directed Ligands in Alzheimer‚Äôs Disease Therapy
Kuca, K. (2018) · BiblioBoard Library Catalog (Open Research Library)
Multi Target Directed Ligand for Alzheimer’s Disease: A Review of Therapeutic Strategies and Advances
Kumar, S., Sharma, V., Happy, & Verma, D. K. K. (2026) · Current Pharmaceutical Research · doi:10.63785/cpr.2026.2.2.292310
Multi-Target-Directed Ligands as an Effective Strategy for the Treatment of Alzheimer’s Disease
Kumar, R., Kumar, V., Kumar, B., Thakur, A., & Dwivedi, A. R. (2021) · Current Medicinal Chemistry · doi:10.2174/0929867328666210512005508 · Cited by 54 · see citing works

Authors: Agis-Torres, A., Sollhuber, M., Fernandez, M., & Sanchez-Montero, J. M.
Affiliations: Universidad Complutense de Madrid (ES)
Venue: Current Neuropharmacology
Publisher: Bentham Science Publishers Ltd.
Published: 2014-01-31
Volume: 12
Issue: 1
Pages: 2-36
ISSN: 1570-159X (ISSN-L)
DOI: 10.2174/1570159x113116660047
PMC: PMC3915347
OpenAlex: W2031507955
Cited by: 202
References: 461
Citations by year: 2026: 10 · 2025: 13 · 2024: 10 · 2023: 12 · 2022: 18 · 2021: 11 · 2020: 18 · 2019: 24 · 2018: 21 · 2017: 25 · 2016: 22 · 2015: 12 · 2014: 6
FWCI: 15.81
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Current Neuropharmacology (publishedVersion)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: Alzheimer's disease, multi-target-directed ligands, Alzheimer's disease therapeutics, disease pathology, therapeutic drug development, complex diseases

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Multi-Target-Directed Ligands and other Therapeutic Strategies in the Search of a Real Solution for Alzheimer’s Disease

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