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
  • [1] Clinical Effects of Tramiprosate in APOE4/4 Homozygous Patients with Mild Alzheimer's Disease Suggest Disease Modification Potential
    Abushakra, S.
    Porsteinsson, A.
    Scheltens, P.
    Sadowsky, C.
    Vellas, B.
    Cummings, J.
    Gauthier, S.
    Hey, J. A.
    Power, A.
    Wang, P.
    Shen, L.
    Tolar, M.
    [J]. JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE, 2017, 4 (03): : 149 - 156
  • [2] Structures of the σ2, receptor enable docking for bioactive ligand discovery
    Alon, Assaf
    Lyu, Jiankun
    Braz, Joao M.
    Tummino, Tia A.
    Craik, Veronica
    O'Meara, Matthew J.
    Webb, Chase M.
    Radchenko, Dmytro S.
    Moroz, Yurii S.
    Huang, Xi-Ping
    Liu, Yongfeng
    Roth, Bryan L.
    Irwin, John J.
    Basbaum, Allan, I
    Shoichet, Brian K.
    Kruse, Andrew C.
    [J]. NATURE, 2021, 600 (7890) : 759 - +
  • [3] Arnold S.E.K., 2022, J. Prev. Alzheimers Dis., V9, pLB11
  • [4] New insights into the genetic etiology of Alzheimer's disease and related dementias
    Bellenguez, Celine
    Kucukali, Fahri
    Jansen, Iris E.
    Kleineidam, Luca
    Moreno-Grau, Sonia
    Amin, Najaf
    Naj, Adam C.
    Campos-Martin, Rafael
    Grenier-Boley, Benjamin
    Andrade, Victor
    Holmans, Peter A.
    Boland, Anne
    Damotte, Vincent
    van der Lee, Sven J.
    Costa, Marcos R.
    Kuulasmaa, Teemu
    Yang, Qiong
    De Rojas, Itziar
    Bis, Joshua C.
    Yaqub, Amber
    Prokic, Ivana
    Chapuis, Julien
    Ahmad, Shahzad
    Giedraitis, Vilmantas
    Aarsland, Dag
    Garcia-Gonzalez, Pablo
    Abdelnour, Carla
    Alarcon-Martin, Emilio
    Alcolea, Daniel
    Alegret, Montserrat
    Alvarez, Ignacio
    Alvarez, Victoria
    Armstrong, Nicola J.
    Tsolaki, Anthoula
    Antunez, Carmen
    Appollonio, Ildebrando
    Arcaro, Marina
    Archetti, Silvana
    Arias Pastor, Alfonso
    Arosio, Beatrice
    Athanasiu, Lavinia
    Bailly, Henri
    Banaj, Nerisa
    Baquero, Miquel
    Barral, Sandra
    Beiser, Alexa
    Pastor, Ana Belen
    Below, Jennifer E.
    Benchek, Penelope
    Benussi, Luisa
    [J]. NATURE GENETICS, 2022, 54 (04) : 412 - 436
  • [5] A Perspective on Multi-target Drugs for Alzheimer's Disease
    Benek, Ondrej
    Korabecny, Jan
    Soukup, Ondrej
    [J]. TRENDS IN PHARMACOLOGICAL SCIENCES, 2020, 41 (07) : 434 - 445
  • [6] Rare genetic variation in fibronectin 1 (FN1) protects against APOEε4 in Alzheimer's disease
    Bhattarai, Prabesh
    Gunasekaran, Tamil Iniyan
    Belloy, Michael E.
    Reyes-Dumeyer, Dolly
    Julich, Dorthe
    Tayran, Hueseyin
    Yilmaz, Elanur
    Flaherty, Delaney
    Turgutalp, Bengisu
    Sukumar, Gauthaman
    Alba, Camille
    McGrath, Elisa Martinez
    Hupalo, Daniel N.
    Bacikova, Dagmar
    Le Guen, Yann
    Lantigua, Rafael
    Medrano, Martin
    Rivera, Diones
    Recio, Patricia
    Nuriel, Tal
    Ertekin-Taner, Nilufer
    Teich, Andrew F.
    Dickson, Dennis W.
    Holley, Scott
    Greicius, Michael
    Dalgard, Clifton L.
    Zody, Michael
    Mayeux, Richard
    Kizil, Caghan
    Vardarajan, Badri N.
    [J]. ACTA NEUROPATHOLOGICA, 2024, 147 (01)
  • [7] Zebrafish as an Experimental and Preclinical Model for Alzheimer?s Disease
    Bhattarai, Prabesh
    Turgutalp, Bengisu
    Kizil, Caghan
    [J]. ACS CHEMICAL NEUROSCIENCE, 2022, 13 (20): : 2939 - 2941
  • [8] Safety and efficacy of pioglitazone for the delay of cognitive impairment in people at risk of Alzheimer's disease (TOMMORROW): a prognostic biomarker study and a phase 3, randomised, double-blind, placebo-controlled trial
    Burns, Daniel K.
    Alexander, Robert C.
    Welsh-Bohmer, Kathleen A.
    Culp, Meredith
    Chiang, Carl
    O'Neil, Janet
    Evans, Rebecca M.
    Harrigan, Patrick
    Plassman, Brenda L.
    Burke, James R.
    Wu, Jingtao
    Lutz, Michael W.
    Haneline, Stephen
    Schwarz, Adam J.
    Schneider, Lon S.
    Yaffe, Kristine
    Saunders, Ann M.
    Ratti, Emiliangelo
    [J]. LANCET NEUROLOGY, 2021, 20 (07) : 537 - 547
  • [9] Improving the generalizability of protein-ligand binding predictions with AI-Bind
    Chatterjee, Ayan
    Walters, Robin
    Shafi, Zohair
    Ahmed, Omair Shafi
    Sebek, Michael
    Gysi, Deisy
    Yu, Rose
    Eliassi-Rad, Tina
    Barabasi, Albert-Laszlo
    Menichetti, Giulia
    [J]. NATURE COMMUNICATIONS, 2023, 14 (01)
  • [10] Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo
    Christ, Maximilian G.
    Huesmann, Heike
    Nagel, Heike
    Kern, Andreas
    Behl, Christian
    [J]. CELLS, 2019, 8 (03)