Multitarget strategies in Alzheimer's disease: benefits and challenges on the road to therapeutics

Rational Polypharmacology: Systematically Identifying and Engaging Multiple Drug Targets To Promote Axon Growth

(2015) Hassan Al-Ali et al.   ACS Chemical Biology

3,4-Dihydro-1,3,5-triazin-2(1H)-ones as the First Dual BACE-1/GSK-3β Fragment Hits against Alzheimer’s Disease

(2015) Federica Prati et al.   ACS Chemical Neuroscience

Tools of the Trade: Investigations into Design Strategies of Small Molecules to Target Components in Alzheimer's Disease

(2015) Jeffrey S. Derrick et al.   CHEMBIOCHEM

Perspectives on Inhibiting β-Amyloid Aggregation through Structure-Based Drug Design

(2015) Pankaj Mishra et al.   ChemMedChem

Multitarget Therapeutic Leads for Alzheimer’s Disease: Quinolizidinyl Derivatives of Bi- and Tricyclic Systems as Dual Inhibitors of Cholinesterases and β-Amyloid (Aβ) Aggregation

(2015) Michele Tonelli et al.   ChemMedChem

From Bitopic Inhibitors to Multitarget Drugs for the Future Treatment of Alzheimer’s Disease

(2015) Daniel Perez et al.   CURRENT MEDICINAL CHEMISTRY

Donepezil–ferulic acid hybrids as anti-Alzheimer drugs

(2015) Mohamed Benchekroun et al.   Future Medicinal Chemistry

Dual inhibition of acetylcholinesterase and butyrylcholinesterase enzymes by allicin

(2015) Suresh Kumar   INDIAN JOURNAL OF PHARMACOLOGY

Novel Levetiracetam Derivatives That Are Effective against the Alzheimer-like Phenotype in Mice: Synthesis, in Vitro, ex Vivo, and in Vivo Efficacy Studies

(2015) Irene Sola et al.   JOURNAL OF MEDICINAL CHEMISTRY

Novel Multitarget-Directed Ligands (MTDLs) with Acetylcholinesterase (AChE) Inhibitory and Serotonergic Subtype 4 Receptor (5-HT4R) Agonist Activities As Potential Agents against Alzheimer’s Disease: The Design of Donecopride

(2015) Christophe Rochais et al.   JOURNAL OF MEDICINAL CHEMISTRY

Modulation of monoamine oxidase (MAO) expression in neuropsychiatric disorders: genetic and environmental factors involved in type A MAO expression

(2015) Makoto Naoi et al.   JOURNAL OF NEURAL TRANSMISSION

Role of sigma-1 receptors in neurodegenerative diseases

(2015) Linda Nguyen et al.   JOURNAL OF PHARMACOLOGICAL SCIENCES

Neuroinflammation in Alzheimer's disease

(2015) Michael T Heneka et al.   LANCET NEUROLOGY

The case for rejecting the amyloid cascade hypothesis

(2015) Karl Herrup   NATURE NEUROSCIENCE

Aβ regulation-based multitarget strategy for drug discovery against Alzheimer’s disease

(2015) Xiaodan Guo et al.   REVIEWS IN THE NEUROSCIENCES

Conjugates of γ-Carbolines and Phenothiazine as new selective inhibitors of butyrylcholinesterase and blockers of NMDA receptors for Alzheimer Disease

(2015) Galina F. Makhaeva et al.   Scientific Reports

First Selective Dual Inhibitors of Tau Phosphorylation and Beta-Amyloid Aggregation, Two Major Pathogenic Mechanisms in Alzheimer’s Disease

(2014) Marica Mariano et al.   ACS Chemical Neuroscience

Multitarget Drug Discovery for Alzheimer's Disease: Triazinones as BACE-1 and GSK-3β Inhibitors

(2014) Federica Prati et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Kinetic and structural analysis of the irreversible inhibition of human monoamine oxidases by ASS234, a multi-target compound designed for use in Alzheimer's disease

(2014) Gerard Esteban et al.   BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS

Shogaol–huprine hybrids: Dual antioxidant and anticholinesterase agents with β-amyloid and tau anti-aggregating properties

(2014) F. Javier Pérez-Areales et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Recent Development of Multifunctional Agents as Potential Drug Candidates for the Treatment of Alzheimer’s Disease

(2014) Natalia Guzior et al.   CURRENT MEDICINAL CHEMISTRY

Effects of Novel Monoamine Oxidases and Cholinesterases Targeting Compounds on Brain Neurotransmitters and Behavior in Rat Model of Vascular Dementia

(2014) Anna Stasiak et al.   CURRENT PHARMACEUTICAL DESIGN

Lessons Learnt from Glycogen Synthase Kinase 3 Inhibitors Development for Alzheimer’s Disease

(2014) Ana Martinez et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

Dual Inhibitors of β-Amyloid Aggregation and Acetylcholinesterase as Multi-Target Anti-Alzheimer Drug Candidates

(2014) Elisabet Viayna et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

Multifunctional Tacrine Derivatives in Alzheimer’s Disease

(2014) Anna Minarini et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

Tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrids as a new family of anti-Alzheimer agents targeting β-amyloid, tau, and cholinesterase pathologies

(2014) Ornella Di Pietro et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Development of dual targeting inhibitors against aggregations of amyloid-β and tau protein

(2014) Shinichiro Fuse et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Polypharmacology: the rise of multitarget drugs over combination therapies

(2014) Michela Rosini   Future Medicinal Chemistry

Synthesis and Multitarget Biological Profiling of a Novel Family of Rhein Derivatives As Disease-Modifying Anti-Alzheimer Agents

(2014) Elisabet Viayna et al.   JOURNAL OF MEDICINAL CHEMISTRY

Polypharmacology: Challenges and Opportunities in Drug Discovery

(2014) Andrew Anighoro et al.   JOURNAL OF MEDICINAL CHEMISTRY

Multitarget Drug Design Strategy: Quinone–Tacrine Hybrids Designed To Block Amyloid-β Aggregation and To Exert Anticholinesterase and Antioxidant Effects

(2014) Eugenie Nepovimova et al.   JOURNAL OF MEDICINAL CHEMISTRY

Monoaminergic neurotransmitter alterations in postmortem brain regions of depressed and aggressive patients with Alzheimer's disease

(2014) Yannick Vermeiren et al.   NEUROBIOLOGY OF AGING

Multi-target Design Strategies in the Context of Alzheimer’s Disease: Acetylcholinesterase Inhibition and NMDA Receptor Antagonism as the Driving Forces

(2014) Michela Rosini et al.   NEUROCHEMICAL RESEARCH

Design of donecopride, a dual serotonin subtype 4 receptor agonist/acetylcholinesterase inhibitor with potential interest for Alzheimer's disease treatment

(2014) C. Lecoutey et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Untangling Amyloid-β, Tau, and Metals in Alzheimer’s Disease

(2013) Masha G. Savelieff et al.   ACS Chemical Biology

The Alzheimer's disease mitochondrial cascade hypothesis: Progress and perspectives

(2013) Russell H. Swerdlow et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

The Bivalent Ligand Approach as a Tool for Improving the in vitro Anti-Alzheimer Multitarget Profile of Dimebon

(2013) Michela Rosini et al.   ChemMedChem

Amyloid β, Glutamate, Excitotoxicity in Alzheimer's Disease: Are We on the Right Track?

(2013) Zaira Esposito et al.   CNS Neuroscience & Therapeutics

Multipotent, Permeable Drug ASS234 Inhibits Aβ Aggregation, Possesses Antioxidant Properties and Protects from Aβ-induced Apoptosis In Vitro

(2013) Irene Bolea et al.   Current Alzheimer Research

Editorial (Hot Topic: Complexity against Complexity: Multitarget Drugs)

(2013) Diego Munoz-Torrero   CURRENT MEDICINAL CHEMISTRY

Polypharmacology in a Single Drug: Multitarget Drugs

(2013) M. L. Bolognesi   CURRENT MEDICINAL CHEMISTRY

Oxidative Stress in Alzheimer’s Disease: Are We Connecting the Dots?

(2013) Michela Rosini et al.   JOURNAL OF MEDICINAL CHEMISTRY

Zyxin is a novel target for beta-amyloid peptide: characterization of its role in Alzheimer's pathogenesis

(2013) Cristina Lanni et al.   JOURNAL OF NEUROCHEMISTRY

A new roadmap for drug development for Alzheimer's disease

(2013) Robert E. Becker et al.   NATURE REVIEWS DRUG DISCOVERY

Blockade of Tau Hyperphosphorylation and Aβ1–42 Generation by the Aminotetrahydrofuran Derivative ANAVEX2-73, a Mixed Muscarinic and σ1 Receptor Agonist, in a Nontransgenic Mouse Model of Alzheimer’s Disease

(2013) Valentine Lahmy et al.   NEUROPSYCHOPHARMACOLOGY

Memantine and Cholinesterase Inhibitors: Complementary Mechanisms in the Treatment of Alzheimer’s Disease

(2013) Chris G. Parsons et al.   NEUROTOXICITY RESEARCH

Early administration of RS 67333, a specific 5-HT4 receptor agonist, prevents amyloidogenesis and behavioral deficits in the 5XFAD mouse model of Alzheimer’s disease

(2013) Patrizia Giannoni et al.   Frontiers in Aging Neuroscience

Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitro and in vivo

(2012) Erin E. Congdon et al.   Autophagy

Synergistic effect of acetylcholinesterase inhibition (donepezil) and 5-HT4 receptor activation (RS67333) on object recognition in mice

(2012) Thomas Freret et al.   BEHAVIOURAL BRAIN RESEARCH

Combining Galantamine and Memantine in Multitargeted, New Chemical Entities Potentially Useful in Alzheimer’s Disease

(2012) Elena Simoni et al.   JOURNAL OF MEDICINAL CHEMISTRY

Propargylamine-derived multitarget-directed ligands: fighting Alzheimer’s disease with monoamine oxidase inhibitors

(2012) Irene Bolea et al.   JOURNAL OF NEURAL TRANSMISSION

Synergistic Effects of Galantamine and Memantine in Attenuating Scopolamine-Induced Amnesia in Mice

(2012) Perrine Busquet et al.   JOURNAL OF PHARMACOLOGICAL SCIENCES

Automated design of ligands to polypharmacological profiles

(2012) Jérémy Besnard et al.   NATURE

Conformational Altered p53 as an Early Marker of Oxidative Stress in Alzheimer's Disease

(2012) Laura Buizza et al.   PLoS One

The serotonergic system in ageing and Alzheimer's disease

(2012) José Julio Rodríguez et al.   PROGRESS IN NEUROBIOLOGY

The First Dual ChE/FAAH Inhibitors: New Perspectives for Alzheimer's Disease?

(2012) Angela Rampa et al.   ACS Medicinal Chemistry Letters

The role of fragment-based and computational methods in polypharmacology

(2011) Giovanni Bottegoni et al.   DRUG DISCOVERY TODAY

Quinolizidinyl derivatives of bi- and tricyclic systems as potent inhibitors of acetyl- and butyrylcholinesterase with potential in Alzheimer’s disease

(2011) B. Tasso et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Exploiting the lipoic acid structure in the search for novel multitarget ligands against Alzheimer’s disease

(2011) Michela Rosini et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Synthesis, Biological Evaluation, and Molecular Modeling of Donepezil andN-[(5-(Benzyloxy)-1-methyl-1H-indol-2-yl)methyl]-N-methylprop-2-yn-1-amine Hybrids as New Multipotent Cholinesterase/Monoamine Oxidase Inhibitors for the Treatment of Alzheimer’s Disease

(2011) Irene Bolea et al.   JOURNAL OF MEDICINAL CHEMISTRY

Alzheimer's disease

(2011) Clive Ballard et al.   LANCET

Recent advances in the multitarget-directed ligands approach for the treatment of Alzheimer's disease

(2011) Rafael León et al.   MEDICINAL RESEARCH REVIEWS

The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics

(2011) Eric Karran et al.   NATURE REVIEWS DRUG DISCOVERY

The basal forebrain cholinergic system in aging and dementia. Rescuing cholinergic neurons from neurotoxic amyloid-β42 with memantine

(2010) Csaba Nyakas et al.   BEHAVIOURAL BRAIN RESEARCH

Control of p53 and NF-κB signaling by WIP1 and MIF: Role in cellular senescence and organismal aging

(2010) Antero Salminen et al.   CELLULAR SIGNALLING

β -Amyloid: A Disease Target or a Synaptic Regulator Affecting Age-Related Neurotransmitter Changes?

(2010) E. Mura et al.   CURRENT PHARMACEUTICAL DESIGN

Alzheimer's disease: strategies for disease modification

(2010) Martin Citron   NATURE REVIEWS DRUG DISCOVERY

Amyloid-β and tau — a toxic pas de deux in Alzheimer's disease

(2010) Lars M. Ittner et al.   NATURE REVIEWS NEUROSCIENCE

Rasagiline: A novel anti-Parkinsonian monoamine oxidase-B inhibitor with neuroprotective activity

(2010) Orly Weinreb et al.   PROGRESS IN NEUROBIOLOGY

The Puzzling Rise and Fall of a Dark-Horse Alzheimer's Drug

(2010) G. Miller   SCIENCE

Alzheimer's Disease: From Pathology to Therapeutic Approaches

(2009) Roland Jakob-Roetne et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Assessment of MAO-B Occupancy in the Brain With PET and [11C]-L-Deprenyl-D2: A Dose-Finding Study With a Novel MAO-B Inhibitor, EVT 301

(2009) J Hirvonen et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

Alzheimer's disease: new approaches to drug discovery

(2009) Maria L Bolognesi et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Designing Multiple Ligands – Medicinal Chemistry Strategies and Challenges

(2009) Richard Morphy et al.   CURRENT PHARMACEUTICAL DESIGN

The neuroprotective effect of ladostigil against hydrogen peroxide-mediated cytotoxicity

(2008) Orly Weinreb et al.   CHEMICO-BIOLOGICAL INTERACTIONS

Acetylcholinesterase Inhibitors as Disease-Modifying Therapies for Alzheimers Disease

(2008) D. Munoz-Torrero   CURRENT MEDICINAL CHEMISTRY

The neuroprotective mechanism of action of the multimodal drug ladostigil

(2008) Orly Weinreb   Frontiers in Bioscience-Landmark

Inhibition of Acetylcholinesterase, β-Amyloid Aggregation, and NMDA Receptors in Alzheimer’s Disease: A Promising Direction for the Multi-target-Directed Ligands Gold Rush

(2008) Michela Rosini et al.   JOURNAL OF MEDICINAL CHEMISTRY

Multi-target-Directed Ligands To Combat Neurodegenerative Diseases

(2008) Andrea Cavalli et al.   JOURNAL OF MEDICINAL CHEMISTRY

The Novel Cholinesterase–Monoamine Oxidase Inhibitor and Antioxidant, Ladostigil, Confers Neuroprotection in Neuroblastoma Cells and Aged Rats

(2008) Orit Bar-Am et al.   JOURNAL OF MOLECULAR NEUROSCIENCE

Functional Convergence of Dopaminergic and Cholinergic Input Is Critical for Hippocampus-Dependent Working Memory

(2008) L. A. B. Wisman et al.   JOURNAL OF NEUROSCIENCE

Network pharmacology: the next paradigm in drug discovery

(2008) Andrew L Hopkins   Nature Chemical Biology

A role for the 5-HT1A, 5-HT4 and 5-HT6 receptors in learning and memory

(2008) M KING et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Prucalopride and donepezil act synergistically to reverse scopolamine-induced memory deficit in C57Bl/6j mice

(2007) M CACHARDCHASTEL et al.   BEHAVIOURAL BRAIN RESEARCH