Neprilysin: an enzyme candidate to slow the progression of Alzheimer's disease.

The American Journal of Pathology
Salim S El-AmouriMark S Kindy

Abstract

It is well established that the extracellular deposition of amyloid beta (Abeta) peptide plays a central role in the development of Alzheimer's disease (AD). Therefore, either preventing the accumulation of Abeta peptide in the brain or accelerating its clearance may slow the rate of AD onset. Neprilysin (NEP) is the dominant Abeta peptide-degrading enzyme in the brain; NEP becomes inactivated and down-regulated during both the early stages of AD and aging. In this study, we investigated the effect of human (h)NEP gene transfer to the brain in a mouse model of AD before the development of amyloid plaques, and assessed how this treatment modality affected the accumulation of Abeta peptide and associated pathogenetic changes (eg, inflammation, oxidative stress, and memory impairment). Overexpression of hNEP for 4 months in young APP/DeltaPS1 double-transgenic mice resulted in reduction in Abeta peptide levels, attenuation of amyloid load, oxidative stress, and inflammation, and improved spatial orientation. Moreover, the overall reduction in amyloidosis and associated pathogenetic changes in the brain resulted in decreased memory impairment by approximately 50%. These data suggest that restoring NEP levels in the brain at the ear...Continue Reading

References

Oct 1, 1989·Journal of Neuroimmunology·S ItagakiD Selkoe
Nov 1, 1985·Archives of Neurology·Z S Khachaturian
Feb 1, 1995·Mutation Research·J RemacleG Rao
Jul 1, 1996·Chemical Research in Toxicology·J S Beckman
Apr 1, 1997·Neurochemistry International·S HuC C Chao
May 15, 1997·The Biochemical Journal·R T DeanM J Davies
Sep 12, 1998·Journal of Virology·H MiyoshiI M Verma
Oct 10, 1998·Journal of Virology·T DullL Naldini
Apr 17, 1999·Cellular Signalling·H Kamata, H Hirata
Jun 13, 2000·Alzheimer Disease and Associated Disorders·H AkiyamaK Ikeda
Jun 20, 2000·Neurobiology of Aging·H AkiyamaT Wyss-Coray
Mar 29, 2001·Physiological Reviews·D J Selkoe
May 26, 2001·Science·N IwataT C Saido
Apr 30, 2002·Free Radical Biology & Medicine·M Flint Beal
Jul 10, 2002·The Journal of Biological Chemistry·M Hasan MohajeriRoger M Nitsch
Sep 5, 2002·Journal of Neuroscience Research·Marina D KirkitadzeDavid B Teplow
Oct 23, 2002·Journal of Neuroscience Research·Nobuhisa IwataTakaomi C Saido
Oct 26, 2002·Science·Dennis J Selkoe
Sep 27, 2003·Biochemical and Biophysical Research Communications·Deng-Shun WangDennis W Dickson
Jan 30, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nobuhisa IwataTakaomi C Saido

❮ Previous
Next ❯

Citations

Sep 21, 2013·Acta Neuropathologica·Patrick L McGeer, Edith G McGeer
Oct 22, 2008·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Kathleen A Maguire-Zeiss, Howard J Federoff
Nov 20, 2008·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Jiqing Xu, Tsuneya Ikezu
Jul 17, 2012·Chemical Reviews·Kasper P Kepp
Nov 1, 2008·The Journal of Biological Chemistry·Hiroaki TaguchiSudhir Paul
Apr 8, 2010·Rejuvenation Research·Sudhir PaulYasuhiro Nishiyama
Jun 8, 2012·Cold Spring Harbor Perspectives in Medicine·Takaomi Saido, Malcolm A Leissring
Dec 6, 2012·Translational Neurodegeneration·Suzhen DongZheng Zhao
Jan 30, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·John B RoseEliezer Masliah
Mar 22, 2014·Journal of Chemical Information and Modeling·Darrick PopeMichael Cascio
Dec 18, 2013·Pharmacology & Therapeutics·Juliana Navarro-YepesRodrigo Franco
Oct 12, 2012·Cell and Tissue Research·Annalisa GrimaldiMagda de Eguileor
Jan 5, 2011·International Journal of Alzheimer's Disease·Nicole T WattNigel M Hooper
Jul 17, 2009·Journal of Neuropathology and Experimental Neurology·James Scott MinersSeth Love
Jul 30, 2011·Journal of Ethnopharmacology·Yuan LiuPengtao Li
Oct 18, 2011·Journal of Neuropathology and Experimental Neurology·James Scott MinersSeth Love
Aug 18, 2012·International Journal of Alzheimer's Disease·N N NalivaevaA J Turner
May 1, 2012·Biomolecules & Therapeutics·Sang-Sun Yoon, Sangmee Ahn Jo
Dec 30, 2014·Journal of Chemical Information and Modeling·Carlos H B da Cruz, G M Seabra
Jan 9, 2015·The International Journal of Neuropsychopharmacology·Huang HuangMing Xiao
Feb 13, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Miguel Chin-ChanBetzabet Quintanilla-Vega
Oct 14, 2014·Frontiers in Aging Neuroscience·J Scott MinersSeth Love
Oct 4, 2014·Frontiers in Aging Neuroscience·Natalia N NalivaevaAnthony J Turner
Jun 30, 2012·Biochemical and Biophysical Research Communications·Yuanli LiFeng Liu
Dec 16, 2016·Nature Reviews. Cardiology·Duncan J Campbell
Jan 11, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Solomon Habtemariam
May 18, 2018·Microbiology and Immunology·Madoka SakaiKeizo Tomonaga
Jan 15, 2009·Journal of Neurochemistry·Peter J CrouchAnthony R White
Apr 29, 2009·The Journal of Comparative Neurology·Howard J Federoff
Aug 2, 2013·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Daniel Saiz-SanchezAlino Martinez-Marcos

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Microglia

Microglia are a type of glial cell found throughout the brain and spinal cord. Microglia have been found to be associated with Alzheimer's disease development and progression. Here are the latest discoveries pertaining to Alzheimer's disease and microglia.

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.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

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.

Astrocytes & Amyloid

Astrocytes are thought to play a role in amyloid production and have been implicated in neurodegenerative diseases such as Alzheimer’s disease. Here is the latest research on the relationship between astrocytes and amyloid.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.