While the extensive hunt for therapeutics combating Alzheimer's disease (AD) has fallen short of delivering effective treatments, breakthroughs towards understanding the disease mechanisms and identifying areas for future research have nevertheless been enabled. The majority of clinical trials with β- and γ-secretase modulators have been suspended from additional studies or terminated due to toxicity issues and health concerns. The lack of progress in developing innovative AD therapies has also prompted a resurgence of interest in more traditional symptomatic treatments with cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists, as well as in the research of immune response modulators. Recently, evidence has emerged showing that inhibitors of arginine metabolism and in particular blockers of arginase, an enzyme that catalyzes the breakdown of L-arginine, could present an effective therapeutic candidate for halting the progression of AD and boosting cognition and memory. In this commentary, we present a brief overview of reports on arginase inhibitors in AD mouse models and discuss emerging advantages and areas for careful consideration on the road to clinical translation.

Faculty of Medicine at Charles University 116 36 Prague Czechia

Institute for Biological and Medical Imaging Helmholtz Zentrum Munich German Research Center for Environmental Health 85764 Neuherberg Germany

International Centre for Neurotherapeutics Dublin City University 9 Dublin Ireland

Munich School of Bioengineering Technical University Munich D 80333 Munich Germany

The National Institute of Mental Health Topolová 748 250 67 Klecany Czechia

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