The activity of blood serum cholinesterases and neprilysin as potential biomarkers of mild-cognitive impairment and Alzheimer’s disease

Журавин, И. А.; Nalivaeva, Natalia N.; Козлова, Д. И.; Kochkina, E. G.; Fedorova, Ya. B.; Гаврилова, С. И.

doi:10.17116/jnevro2015115112110-117

Cited by 26 publications

(12 citation statements)

References 53 publications

(45 reference statements)

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“…A recent meta‐analysis of NEP levels in AD concluded that NEP expression and activity were decreased in the cortex of elderly AD patients adding to the accumulation of evidence that NEP could be a valuable therapeutic target to combat the disease (Zhang et al, ). Furthermore, we have reported reduced NEP activity in the blood plasma of early AD patients (Zhuravin et al, ) in line with earlier studies showing that CSF NEP is reduced in prodromal AD (Maruyama et al, ).…”

Section: The Key Adessupporting

confidence: 91%

Targeting amyloid clearance in Alzheimer's disease as a therapeutic strategy

Nalivaeva

Turner

2019

British J Pharmacology

143

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Targeting the amyloid‐β (Aβ) peptide cascade has been at the heart of therapeutic developments in Alzheimer's disease (AD) research for more than 25 years, yet no successful drugs have reached the marketplace based on this hypothesis. Nevertheless, the genetic and other evidence remains strong, if not overwhelming, that Aβ is central to the disease process. Most attention has focused on the biosynthesis of Aβ from its precursor protein through the successive actions of the β‐ and γ‐secretases leading to the development of inhibitors of these membrane proteases. However, the levels of Aβ are maintained through a balance of its biosynthesis and clearance, which occurs both through further proteolysis by a family of amyloid‐degrading enzymes (ADEs) and by a variety of transport processes. The development of late‐onset AD appears to arise from a failure of these clearance mechanisms rather than by overproduction of the peptide. This review focuses on the nature of these clearance mechanisms, particularly the various proteases known to be involved, and their regulation and potential as therapeutic targets in AD drug development. The majority of the ADEs are zinc metalloproteases [e.g., the neprilysin (NEP) family, insulin‐degrading enzyme, and angiotensin converting enzymes (ACE)]. Strategies for up‐regulating the expression and activity of these enzymes, such as genetic, epigenetic, stem cell technology, and other pharmacological approaches, will be highlighted. Modifiable physiological mechanisms affecting the efficiency of Aβ clearance, including brain perfusion, obesity, diabetes, and sleep, will also be outlined. These new insights provide optimism for future therapeutic developments in AD research. Linked Articles This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc

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Section: The Key Adessupporting

confidence: 91%

Targeting amyloid clearance in Alzheimer's disease as a therapeutic strategy

Nalivaeva

Turner

2019

British J Pharmacology

143

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“…Reduced CSF NEP activity levels have been shown to occur in early AD, suggesting that altered CSF NEP activity levels may also be predictive of the progression of dementia ( Maetzler et al, 2010 ). There are also reports on reduced NEP activity in blood plasma in individuals with mild cognitive impairment and AD patients ( Zhuravin et al, 2015 ), which are in line with studies showing that NEP is reduced in CSF in prodromal AD ( Maruyama et al 2005 ).…”

Section: Role Of Nep In Diseasessupporting

confidence: 80%

Neprilysin expression and functions in development, ageing and disease

Наливаева

Журавин

Turner

2020

Mechanisms of Ageing and Development

118

103

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“…Interestingly, the downregulation of neprilysin in the AD brain appears to begin at an early stage. Neprilysin activity is reduced in the blood serum of patients with MCI [431] and neprilysin levels were reported to decline in the CSF of patients with early AD and amnestic MCI progressing to AD [432]. Neprilysin polymorphisms have been associated with the appearance of CAA and are correlated with its severity [433].…”

Section: Implications For Therapy and Drug Designmentioning

confidence: 99%

Vascular Dysfunction in Alzheimer’s Disease: A Prelude to the Pathological Process or a Consequence of It?

Govindpani

McNamara

Smith

et al. 2019

JCM

178

142

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Alzheimer’s disease (AD) is the most prevalent form of dementia. Despite decades of research following several theoretical and clinical lines, all existing treatments for the disorder are purely symptomatic. AD research has traditionally been focused on neuronal and glial dysfunction. Although there is a wealth of evidence pointing to a significant vascular component in the disease, this angle has been relatively poorly explored. In this review, we consider the various aspects of vascular dysfunction in AD, which has a significant impact on brain metabolism and homeostasis and the clearance of β-amyloid and other toxic metabolites. This may potentially precede the onset of the hallmark pathophysiological and cognitive symptoms of the disease. Pathological changes in vessel haemodynamics, angiogenesis, vascular cell function, vascular coverage, blood-brain barrier permeability and immune cell migration may be related to amyloid toxicity, oxidative stress and apolipoprotein E (APOE) genotype. These vascular deficits may in turn contribute to parenchymal amyloid deposition, neurotoxicity, glial activation and metabolic dysfunction in multiple cell types. A vicious feedback cycle ensues, with progressively worsening neuronal and vascular pathology through the course of the disease. Thus, a better appreciation for the importance of vascular dysfunction in AD may open new avenues for research and therapy.

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The activity of blood serum cholinesterases and neprilysin as potential biomarkers of mild-cognitive impairment and Alzheimer’s disease

Cited by 26 publications

References 53 publications

Targeting amyloid clearance in Alzheimer's disease as a therapeutic strategy

Targeting amyloid clearance in Alzheimer's disease as a therapeutic strategy

Neprilysin expression and functions in development, ageing and disease

Vascular Dysfunction in Alzheimer’s Disease: A Prelude to the Pathological Process or a Consequence of It?

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