Powering Amyloid Beta Degrading Enzymes: A Possible Therapy for Alzheimer's Disease

Neurochemical Research
Nkumbu L SikanyikaSanjaya Kuruppu

Abstract

The accumulation of amyloid beta (Aβ) in the brain is believed to play a central role in the development and progression of Alzheimer's disease. Revisions to the amyloid cascade hypothesis now acknowledge the dynamic equilibrium in which Aβ exists and the importance of enzymes involved in the production and breakdown of Aβ in maintaining healthy Aβ levels. However, while a wealth of pharmacological and immunological therapies are being generated to inhibit the Aβ-producing enzymes, β-site APP cleavage enzyme 1 and γ-secretase, the therapeutic potential of stimulating Aβ-degrading enzymes such as neprilysin, endothelin-converting enzyme-1 and insulin-degrading enzyme remains relatively unexplored. Recent evidence indicates that increasing Aβ degradation as opposed to inhibiting synthesis is a more effective strategy to prevent Aβ build-up. Therefore Aβ degrading enzymes have become valuable targets of therapy. In this review, we discuss the pathway of Aβ synthesis and clearance along with the opportunities they present for therapeutic intervention, the benefits of increasing the expression/activity of Aβ-degrading enzymes, and the untapped therapeutic potential of enzyme activation.

References

Apr 10, 1992·Science·J A Hardy, G A Higgins
Mar 29, 2001·Physiological Reviews·D J Selkoe
Apr 20, 2001·European Journal of Medicinal Chemistry·G Dannhardt, W Kiefer
May 5, 2001·The Journal of Biological Chemistry·E A EckmanC B Eckman
May 12, 2001·Science·E S Istvan, J Deisenhofer
Sep 19, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhi-Xing Yao, Vassilios Papadopoulos
Dec 5, 2002·The Journal of Biological Chemistry·Elizabeth A EckmanChristopher B Eckman
Mar 14, 2003·Proceedings of the National Academy of Sciences of the United States of America·Wesley FarrisSuzanne Guenette
Jun 24, 2003·The American Journal of Cardiology·Samy I McFarlaneJames R Sowers
Aug 5, 2003·The Journal of Clinical Investigation·Jason L EriksenTodd E Golde
Sep 15, 2004·Proceedings of the National Academy of Sciences of the United States of America·Iftach Dolev, Daniel M Michaelson
Apr 7, 2006·The Journal of Pharmacy and Pharmacology·Shereen Ayoub, Matthias F Melzig
Oct 27, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ke-Jie YinJin-Moo Lee
Mar 7, 2008·Neuro-degenerative Diseases·Yotam NisemblatDaniel M Michaelson
Apr 18, 2008·World Journal of Gastroenterology : WJG·Xi JinYou-Ming Li
May 7, 2008·Neurology·Steven C VladDavid T Felson
Jun 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·J Steven JacobsenMenelas N Pangalos
Jan 2, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Daniela PuzzoOttavio Arancio
Feb 7, 2009·Journal of Neurochemistry·Michela GuglielmottoMassimo Tabaton
Jul 25, 2009·Molecular Neurodegeneration·Rina YaminCarmela R Abraham
Nov 26, 2009·Molecular Neurodegeneration·Ganesh M Shankar, Dominic M Walsh
Dec 17, 2009·JAMA : the Journal of the American Medical Association·Robert C GreenUNKNOWN Tarenflurbil Phase 3 Study Group
Jan 22, 2010·Current Alzheimer Research·R A Marr, B J Spencer
Mar 17, 2010·Neuromolecular Medicine·Vivian W ChowMarc Gleichmann
Aug 20, 2010·Nature Reviews. Endocrinology·Francjan J van Spronsen
Sep 10, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hans ZempelEva-Maria Mandelkow
Dec 15, 2010·Science·Kwasi G MawuenyegaRandall J Bateman
Jan 5, 2011·Toxicon : Official Journal of the International Society on Toxinology·Brian L Furman
Jan 13, 2011·The American Journal of Pathology·Daniel HafezRobert A Marr
May 27, 2011·Science Translational Medicine·Jasvinder K AtwalRyan J Watts
Aug 13, 2011·Toxicon : Official Journal of the International Society on Toxinology·Antonio C M CamargoSolange M T Serrano
Aug 30, 2011·The Journal of Biological Chemistry·Ellen KilgerJanaky Coomaraswamy

❮ Previous
Next ❯

Citations

Sep 15, 2020·Journal of Alzheimer's Disease : JAD·Tak-Ho ChuPeter K Stys
Mar 22, 2020·International Journal of Molecular Sciences·Tiago GiãoIsabel Cardoso
Jul 23, 2020·Scientific Reports·Dongying YangXinli Lin
May 16, 2020·3 Biotech·Maruti J Dhanavade, Kailas D Sonawane
May 8, 2020·Oxidative Medicine and Cellular Longevity·Xin-Yi LuShi-Jie Zhang
Jul 1, 2020·Expert Opinion on Biological Therapy·Saptashwa DattaHatem Zayed
Oct 15, 2020·Reviews in Endocrine & Metabolic Disorders·Rout George KerrySabuj Sahoo
Feb 19, 2021·Biomedical Materials·Qian WangLizeng Gao
Jul 25, 2021·International Journal of Molecular Sciences·Namdoo Kim, Hyuck Jin Lee
Sep 20, 2021·Drug Discovery Today·Jennifer N Hennigan, Michael D Lynch
Aug 26, 2021·Current Alzheimer Research·Anne Kasus-JacobiHeloise Anne Pereira

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.