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Front. Aging Neurosci. | doi: 10.3389/fnagi.2019.00317

Dreaming of a new world where Alzheimer’s is a treatable disorder

Marcella Catania1, Giorgio Giaccone1,  Mario Salmona2, Fabrizio Tagliavini1 and  Giuseppe Di Fede1*
  • 1Carlo Besta Neurological Institute (IRCCS), Italy
  • 2Istituto Di Ricerche Farmacologiche Mario Negri, Italy

Alzheimer’s disease (AD) is the most common form of dementia. It’s a chronic and untreatable neurodegenerative disease with irreversible progression and has important social and economic implications in terms of direct medical and social care costs. Despite prolonged and expensive efforts employed by the scientific community over the last few decades, no effective treatments are still available for patients, and the development of disease-modifying drugs is now a really urgent need. The recent failure of clinical trials based on the immunotherapeutic approach against amyloid-β protein questioned the validity of the ‘amyloid cascade hypothesis’ as the molecular machinery causing the disease. Indeed, most attempts to design effective treatments for AD have been based until now on molecular targets suggested to be implicated in AD pathogenesis by the amyloid cascade hypothesis. However, mounting evidence from scientific literature supports the view of AD as a multifactorial disease that results from the concomitant action of multiple molecular players. This view, together with the lack of success of the disease-modifying single-target approaches, strongly suggests that AD drug design needs to be shifted towards multi-targeted compounds or drug combinations acting synergistically on the main core features of disease pathogenesis. The discovery of drug candidates targeting multiple factors involved in AD would greatly improve drug development. So, it is reasonable that upcoming strategies for the design of preventive and/or therapeutic agents for AD point to a multi-pronged approach including more than one druggable target to definitely defeat the disease.

Keywords: Alzheimer, amyloid-beta, drug, Multi-target, tau, Dementia, therapy, neurodegenerative, Amyloid cascade hypothesis, amyloid precursor protein, BACE, secretase, Disease-modifying, biometal ions Multi-target strategy against AD

Received: 28 Aug 2019; Accepted: 01 Nov 2019.

Copyright: © 2019 Catania, Giaccone, Salmona, Tagliavini and Di Fede. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Giuseppe Di Fede, Carlo Besta Neurological Institute (IRCCS), Milan, Lombardy, Italy, giuseppe.difede@istituto-besta.it