Can Arginase Inhibitors Be the Answer to Therapeutic Challenges in Alzheimer's Disease?

Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics
Saak Victor Ovsepian, Valerie Bríd O'Leary

Abstract

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.

References

Feb 1, 1984·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M D AbeloffS B Baylin
Nov 10, 1998·The Biochemical Journal·G Wu, S M Morris
Dec 4, 2003·Neurobiology of Aging·Salvatore OddoFrank M LaFerla
Jun 9, 2004·Protein and Peptide Letters·Dominic M Walsh, Dennis J Selkoe
Jan 19, 2007·Proceedings of the National Academy of Sciences of the United States of America·Fumio OhtaLouis J Ignarro
Jan 25, 2007·Nature Reviews. Molecular Cell Biology·Christian Haass, Dennis J Selkoe
May 22, 2007·The Journal of Nutrition·Sidney M Morris
Feb 21, 2009·BMC Medicine·Michael S Rafii, Paul S Aisen
Oct 16, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Robert VassarPhilip C Wong
Jul 27, 2010·Current Opinion in Neurobiology·Ye Zhang, Ben A Barres
Aug 10, 2010·Journal of Alzheimer's Disease : JAD·Franck HansmannelJean-Charles Lambert
Apr 23, 2011·Current Topics in Medicinal Chemistry·Bruno P Imbimbo, Giuseppe A M Giardina
Jul 31, 2013·Neuropharmacology·R AnandAbbas Ali Mahdi
May 24, 2014·Neuron·Tara L Spires-Jones, Bradley T Hyman
Nov 25, 2014·Cell·Bart De Strooper
Apr 17, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Matthew J KanCarol A Colton
May 2, 2015·Trends in Pharmacological Sciences·Ruth B CaldwellR William Caldwell
May 24, 2015·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Saak V OvsepianLaszlo Zaborszky
Nov 3, 2015·Biochemical and Biophysical Research Communications·Stefano PatassiniGarth J S Cooper
Oct 18, 2016·Clinical Nutrition : Official Journal of the European Society of Parenteral and Enteral Nutrition·W Kyle MitchellPhilip J Atherton
Nov 25, 2016·Cell Death & Disease·Esraa ShoshaS Priya Narayanan
Feb 25, 2018·European Journal of Medicinal Chemistry·Devendra KumarSushil Kumar Singh
Mar 2, 2018·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Saak V OvsepianJ Oliver Dolly
May 3, 2018·The New England Journal of Medicine·Michael F EganDavid Michelson

❮ Previous
Next ❯

Citations

Jun 6, 2020·Frontiers in Immunology·Tomasz M GrzywaJakub Golab
May 16, 2021·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Claire André, Yves Claude Guillaume

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
light microscopy

Related Concepts

Related Feeds

Alzheimer's Disease: Animal Models

Alzheimer's disease is a neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.