Multi-target drugs for Alzheimer's disease

被引:7
作者
Turgutalp, Bengisu [1 ,2 ]
Kizil, Caghan [1 ,2 ,3 ]
机构
[1] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, Irving Med Ctr, 650 West 168th St, New York, NY 10032 USA
[2] Columbia Univ, Irving Med Ctr, Dept Neurol, 710 West 168th St, New York, NY 10032 USA
[3] Columbia Univ, Irving Med Ctr, Gertrude H Sergievsky Ctr, Coll Phys & Surg, 630 West 168th St, New York, NY 10032 USA
关键词
DONEPEZIL; BIOMARKERS; RECEPTORS; COGNITION; BRAIN; MICE; CARE;
D O I
10.1016/j.tips.2024.05.005
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Alzheimer's disease (AD), a leading cause of dementia, increasingly challenges our healthcare systems and society. Traditional therapies aimed at single targets have fallen short owing to the complex, multifactorial nature of AD that necessitates simultaneous targeting of various disease mechanisms for clinical success. Therefore, targeting multiple pathologies at the same time could provide a synergistic therapeutic effect. The identification of new disease targets beyond the classical hallmarks of AD offers a fertile ground for the design of new multitarget drugs (MTDs), and building on existing compounds have the potential to yield in successful disease modifying therapies. This review discusses the evolving landscape of MTDs, focusing on their potential as AD therapeutics. Analysis of past and current trials of compounds with multi-target activity underscores the capacity of MTDs to offer synergistic therapeutic effects, and the flourishing genetic understanding of AD will inform and inspire the development of MTD-based AD therapies.
引用
收藏
页码:628 / 638
页数:11
相关论文
共 85 条
  • [51] Cross species systems biology discovers glial DDR2, STOM, and KANK2 as therapeutic targets in progressive supranuclear palsy
    Min, Yuhao
    Wang, Xue
    Is, Ozkan
    Patel, Tulsi A.
    Gao, Junli
    Reddy, Joseph S.
    Quicksall, Zachary S.
    Nguyen, Thuy
    Lin, Shu
    Tutor-New, Frederick Q.
    Chalk, Jessica L.
    Mitchell, Adriana O.
    Crook, Julia E.
    Nelson, Peter T.
    Van Eldik, Linda J.
    Golde, Todd E.
    Carrasquillo, Minerva M.
    Dickson, Dennis W.
    Zhang, Ke
    Allen, Mariet
    Ertekin-Taner, Niluefer
    [J]. NATURE COMMUNICATIONS, 2023, 14 (01)
  • [52] Morphy R, 2008, PRACTICE OF MEDICINAL CHEMISTRY, 3RD EDITION, P549, DOI 10.1016/B978-0-12-374194-3.00027-5
  • [53] Insights into Alzheimer's disease from single-cell genomic approaches
    Murdock, Mitchell H.
    Tsai, Li-Huei
    [J]. NATURE NEUROSCIENCE, 2023, 26 (02) : 181 - 195
  • [54] Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer's Disease drug candidate
    Nemergut, Michal
    Marques, Sergio M.
    Uhrik, Lukas
    Vanova, Tereza
    Nezvedova, Marketa
    Gadara, Darshak Chandulal
    Jha, Durga
    Tulis, Jan
    Novakova, Veronika
    Planas-Iglesias, Joan
    Kunka, Antonin
    Legrand, Anthony
    Hribkova, Hana
    Pospisilova, Veronika
    Sedmik, Jiri
    Raska, Jan
    Prokop, Zbynek
    Damborsky, Jiri
    Bohaciakova, Dasa
    Spacil, Zdenek
    Hernychova, Lenka
    Bednar, David
    Marek, Martin
    [J]. MOLECULAR NEURODEGENERATION, 2023, 18 (01)
  • [55] Treatment with glucagon-like peptide-1 receptor agonists and incidence of dementia: Data from pooled double-blind randomized controlled trials and nationwide disease and prescription registers
    Norgaard, Caroline Holm
    Friedrich, Sarah
    Hansen, Charlotte Thim
    Gerds, Thomas
    Ballard, Clive
    Moller, Daniel Vega
    Knudsen, Lotte Bjerre
    Kvist, Kajsa
    Zinman, Bernard
    Holm, Ellen
    Torp-Pedersen, Christian
    Morch, Lina Steinrud
    [J]. ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS, 2022, 8 (01)
  • [56] Tauroursodeoxycholic Acid Attenuates Diet-Induced and Age-Related Peripheral Endoplasmic Reticulum Stress and Cerebral Amyloid Pathology in a Mouse Model of Alzheimer's Disease
    Ochiai, T.
    Nagayama, T.
    Matsui, K.
    Amano, K.
    Sano, T.
    Wakabayashi, T.
    Iwatsubo, T.
    [J]. JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE, 2021, 8 (04): : 483 - 494
  • [57] Integrating synthetic accessibility with AI-based generative drug design
    Parrot, Maud
    Tajmouati, Hamza
    da Silva, Vinicius Barros Ribeiro
    Atwood, Brian Ross
    Fourcade, Robin
    Gaston-Mathe, Yann
    Do Huu, Nicolas
    Perron, Quentin
    [J]. JOURNAL OF CHEMINFORMATICS, 2023, 15 (01)
  • [58] Turning Donepezil into a Multi-Target-Directed Ligand through a Merging Strategy
    Perone, Rosaria
    Albertini, Claudia
    Uliassi, Elisa
    Di Pietri, Flaminia
    de Sena Murteira Pinheiro, Pedro
    Petralla, Sabrina
    Rizzardi, Nicola
    Fato, Romana
    Pulkrabkova, Lenka
    Soukup, Ondrej
    Tramarin, Anna
    Bartolini, Manuela
    Bolognesi, Maria Laura
    [J]. CHEMMEDCHEM, 2021, 16 (01) : 187 - 198
  • [59] Fragment-Based Discovery of an Apolipoprotein E4 (apoE4) Stabilizer
    Petros, Andrew M.
    Korepanova, Alla
    Jakob, Clarissa G.
    Qiu, Wei
    Panchal, Sanjay C.
    Wang, Jie
    Dietrich, Justin D.
    Brewer, Jason T.
    Pohlki, Frauke
    Kling, Andreas
    Wilcox, Kyle
    Lakics, Viktor
    Bahnassawy, Lamiaa
    Reinhardt, Peter
    Partha, Sarathy Karunan
    Bodelle, Pierre M.
    Lake, Marc
    Charych, Erik I.
    Stoll, Vincent S.
    Sun, Chaohong
    Mohler, Eric G.
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2019, 62 (08) : 4120 - 4130
  • [60] CHF5074 (CSP-1103) INDUCES MICROGLIA ALTERNATIVE ACTIVATION IN PLAQUE-FREE TG2576 MICE AND PRIMARY GLIAL CULTURES EXPOSED TO BETA-AMYLOID
    Porrini, V.
    Lanzillotta, A.
    Branca, C.
    Benarese, M.
    Parrella, E.
    Lorenzini, L.
    Calza, L.
    Flaibani, R.
    Spano, P. F.
    Imbimbo, B. P.
    Pizzi, M.
    [J]. NEUROSCIENCE, 2015, 302 : 112 - 120