Current and emerging avenues for Alzheimer's disease drug targets

R. Loera‐Valencia; A. Cedazo‐Minguez; P.A. Kenigsberg; G. Page; A.I. Duarte; P. Giusti; M. Zusso; P. Robert; G. B. Frisoni; Annamaria Cattaneo; M. Zille; J. Boltze; N. Cartier; L. Buee; G. Johansson; B. Winblad

doi:10.1111/joim.12959

journal article Open Access Aug 29, 2019

Current and emerging avenues for Alzheimer's disease drug targets

A. Cedazo‐Minguez P.A. Kenigsberg G. Page A.I. Duarte P. Giusti M. Zusso P. Robert G. B. Frisoni Annamaria Cattaneo M. Zille J. Boltze N. Cartier L. Buee G. Johansson B. Winblad

Journal of Internal Medicine Vol. 286 No. 4 pp. 398-437 · Wiley

View at Publisher Save 10.1111/joim.12959

Abstract

AbstractAlzheimer's disease (AD), the most frequent cause of dementia, is escalating as a global epidemic, and so far, there is neither cure nor treatment to alter its progression. The most important feature of the disease is neuronal death and loss of cognitive functions, caused probably from several pathological processes in the brain. The main neuropathological features of AD are widely described as amyloid beta (Aβ) plaques and neurofibrillary tangles of the aggregated protein tau, which contribute to the disease. Nevertheless, AD brains suffer from a variety of alterations in function, such as energy metabolism, inflammation and synaptic activity. The latest decades have seen an explosion of genes and molecules that can be employed as targets aiming to improve brain physiology, which can result in preventive strategies for AD. Moreover, therapeutics using these targets can help AD brains to sustain function during the development of AD pathology. Here, we review broadly recent information for potential targets that can modify AD through diverse pharmacological and nonpharmacological approaches including gene therapy. We propose that AD could be tackled not only using combination therapies including Aβ and tau, but also considering insulin and cholesterol metabolism, vascular function, synaptic plasticity, epigenetics, neurovascular junction and blood–brain barrier targets that have been studied recently. We also make a case for the role of gut microbiota in AD. Our hope is to promote the continuing research of diverse targets affecting AD and promote diverse targeting as a near‐future strategy.

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References

419

[1]

10.1016/j.jalz.2007.04.381

[2]

10.1016/j.jalz.2010.11.007

[3]

10.1016/s0140-6736(05)67889-0

[4]

10.1016/s1474-4422(16)00062-4

[5]

10.1016/s0140-6736(06)68770-9

[6]

10.1001/jama.1997.03550160069041

[7]

10.1016/j.jalz.2012.11.007

[8]

10.1016/j.jalz.2016.07.150

[9]

10.1186/s13195-016-0188-8

[10]

10.1016/j.jalz.2012.11.006

[11]

10.1016/j.nbt.2008.01.002

[12]

10.1136/bmjopen-2017-019540

[13]

10.1111/joim.12191

[14]

10.1016/s1474-4422(10)70119-8

[15]

10.1126/science.1566067

[16]

10.1111/jnc.13632

[17]

10.1093/brain/awx059

[18]

10.1016/bs.pmbts.2016.12.016

[19]

10.1016/j.cell.2015.12.056

[20]

10.1007/s00401-013-1177-7

[21]

10.1016/j.biopsych.2013.04.011

[22]

10.1111/joim.12759

[23]

10.1212/wnl.0000000000004827

[24]

10.1002/hbm.23948

[25]

10.1016/j.neuroimage.2015.03.035

[26]

10.1016/j.neurobiolaging.2016.03.025

[27]

10.1007/s004010050508

[28]

10.1016/j.neurobiolaging.2005.09.012

[29]

10.1016/j.jalz.2005.11.003

[30]

10.1523/jneurosci.3501-06.2007

[31]

10.1016/s0006-8993(01)03058-x

[32]

10.1016/j.celrep.2015.09.062

[33]

10.1111/j.1471-4159.2006.04040.x

[34]

10.1155/2016/6427537

[35]

10.1186/s13195-016-0195-9

[36]

10.1007/978-3-642-45106-5_1

[37]

10.1038/ncomms12540

[38]

10.1007/s12311-011-0342-6

[39]

10.1017/s1740925x10000244

[40]

10.1016/j.jneuroim.2009.11.002

[41]

10.1055/s-0029-1237423

[42]

10.1016/j.neurobiolaging.2011.02.025

[43]

Neal M "Epigenetic regulation of astrocyte function in neuroinflammation and neurodegeneration" Biochim Biophys Acta (1864)

[44]

10.1007/s12017-013-8266-6

[45]

10.1074/jbc.m608236200

[46]

10.1016/b978-0-12-415795-8.00004-0

[47]

Putteeraj M "MicroRNA dysregulation in Alzheimer's disease" CNS Neurol Disord Drug Targets (2018)

[48]

10.1016/j.nbd.2014.05.034

[49]

10.1016/s1474-4422(15)70016-5

[50]

10.1016/b978-0-444-63432-0.00003-7

Showing 50 of 419 references

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Metrics

122

Citations

419

References

Details

Published: Aug 29, 2019
Vol/Issue: 286(4)
Pages: 398-437
License: View

Authors

R

R. Loera‐Valencia

Division of Neurogeriatrics Centre for Alzheimer Research Department of Neurobiology, Care Sciences and Society Karolinska Institutet Solna Sweden

A

A. Cedazo‐Minguez

Division of Neurogeriatrics Centre for Alzheimer Research Department of Neurobiology, Care Sciences and Society Karolinska Institutet Solna Sweden

P

P.A. Kenigsberg

Fondation Médéric Alzheimer Paris France

G

G. Page

Neurovascular Unit and Cognitive impairments – EA3808 University of Poitiers Poitiers France

A

A.I. Duarte

CNC‐ Center for Neuroscience and Cell Biology University of Coimbra Coimbra Portugal; Institute for Interdisciplinary Research (IIIUC) University of Coimbra Coimbra Portugal

P

P. Giusti

Dipartimento di Scienze del Farmaco Università degli Studi di Padova Padova Italy

M

M. Zusso

Dipartimento di Scienze del Farmaco Università degli Studi di Padova Padova Italy

P

P. Robert

CoBTeK ‐ lab CHU Nice University Côte d'Azur Nice France

G

G. B. Frisoni

Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli Brescia

A

Annamaria Cattaneo

Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli Brescia

M

M. Zille

Institute of Experimental and Clinical Pharmacology and Toxicology Lübeck Germany

J

J. Boltze

School of Life Sciences The University of Warwick Coventry UK

N

N. Cartier

Preclinical research platform INSERM U1169/MIRCen Commissariat à l’énergie atomique Fontenay aux Roses France; Université Paris‐Sud Orsay France

L

L. Buee

Alzheimer & Tauopathies LabEx DISTALZ CHU‐Lille Inserm Univ. Lille Lille France

G

G. Johansson

Division of Neurogeriatrics Centre for Alzheimer Research Department of Neurobiology, Care Sciences and Society Karolinska Institutet Solna Sweden

B

B. Winblad

Division of Neurogeriatrics Centre for Alzheimer Research Department of Neurobiology, Care Sciences and Society Karolinska Institutet Solna Sweden; Theme Aging Karolinska University Hospital Stockholm Sweden

Funding

Vetenskapsrådet

Fundação para a Ciência e a Tecnologia Award: PTDC/SAU‐TOX/117481/2010

Cite This Article

R. Loera‐Valencia, A. Cedazo‐Minguez, P.A. Kenigsberg, et al. (2019). Current and emerging avenues for Alzheimer's disease drug targets. Journal of Internal Medicine, 286(4), 398-437. https://doi.org/10.1111/joim.12959

Current and emerging avenues for Alzheimer's disease drug targets

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