Study of the possible effect of sacubitril/valsartan combination versus valsartan on the cognitive function in Alzheimer’s disease model in rats

Hussein, Abdallah Salah El-Din; Nour, Rahma Kamal El-Din Abou-El; Khorshid, Omayma; Osman, Ashraf

doi:10.1177/03946320231161469

Cited by 4 publications

(4 citation statements)

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“…Experimental study NEP inhibitors trigger AD-like diseases in mice Hüttenrauch et al 44 Experimental study LCZ696 increased Aβ concentration in the CSF but not in the brain Bavishi et al 43 Experimental study LCZ696 accelerates AD progression in animals Vodovar et al 47 Experimental study Long-term effects of NEP inhibitors promote AD and late-onset axonal polyneuropathy Auer-Grumbach et al 41 Experimental study LCZ696 increases AD risk compared with valsartan alone in rats El-din Hussein et al 48 Experimental study LCZ696 accelerates colchicine-induced cognitive impairment in rats Hammadi El-din Hussein et al 50 Preclinical studies LCZ696 has a neuroprotective effect by inhibiting homocysteine-induced BBB injury…”

Section: Study Type Findingsmentioning

confidence: 99%

“…Besides, NEP inhibitors increase the risk of developing late‐onset axonal polyneuropathy 41 . An updated experimental study demonstrated that LCZ696 increases AD risk compared with valsartan alone in rats 48 . Valsartan can decrease the risk of AD development as it selectively blocks AT 1 R as RAS inhibitors have been associated with the reduction of brain damage in different experimental and clinical models of neurodegenerative diseases 49 .…”

Section: Nep Inhibitors In Admentioning

confidence: 99%

“… 41 An updated experimental study demonstrated that LCZ696 increases AD risk compared with valsartan alone in rats. 48 Valsartan can decrease the risk of AD development as it selectively blocks AT 1 R as RAS inhibitors have been associated with the reduction of brain damage in different experimental and clinical models of neurodegenerative diseases. 49 In addition, LCZ696 extravagant colchicine‐induced cognitive impairment in rats by increasing Aβ accumulation, oxidative stress and inflammation compared to valsartan alone.…”

Section: Nep Inhibitors In Admentioning

confidence: 99%

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Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective

Ali,

Al‐Kuraishy,

Al‐Gareeb

et al. 2023

J Cellular Molecular Medi

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Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease with multifaceted neuropathological disorders. AD is characterized by intracellular accumulation of phosphorylated tau proteins and extracellular deposition of amyloid beta (Aβ). Various protease enzymes, including neprilysin (NEP), are concerned with the degradation and clearance of Aβ. Indeed, a defective neuronal clearance pathway due to the dysfunction of degradation enzymes might be a possible mechanism for the accumulation of Aβ and subsequent progression of AD neuropathology. NEP is one of the most imperative metalloproteinase enzymes involved in the clearance of Aβ. This review aimed to highlight the possible role of NEP inhibitors in AD. The combination of sacubitril and valsartan which is called angiotensin receptor blocker and NEP inhibitor (ARNI) may produce beneficial and deleterious effects on AD neuropathology. NEP inhibitors might increase the risk of AD by the inhibition of Aβ clearance, and increase brain bradykinin (BK) and natriuretic peptides (NPs), which augment the pathogenesis of AD. These verdicts come from animal model studies, though they may not be applied to humans. However, clinical studies revealed promising safety findings regarding the use of ARNI. Moreover, NEP inhibition increases various neuroprotective peptides involved in inflammation, glucose homeostasis and nerve conduction. Also, NEP inhibitors may inhibit dipeptidyl peptidase 4 (DPP4) expression, ameliorating insulin and glucagon‐like peptide 1 (GLP‐1) levels. These findings proposed that NEP inhibitors may have a protective effect against AD development by increasing GLP‐1, neuropeptide Y (NPY) and substance P, and deleterious effects by increasing brain BK. Preclinical and clinical studies are recommended in this regard.

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Section: Study Type Findingsmentioning

confidence: 99%

Section: Nep Inhibitors In Admentioning

confidence: 99%

Section: Nep Inhibitors In Admentioning

confidence: 99%

See 1 more Smart Citation

Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective

Ali,

Al‐Kuraishy,

Al‐Gareeb

et al. 2023

J Cellular Molecular Medi

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“…A recent study assessed the effects of sacubitril/valsartan (a relatively new antihypertensive combination) in comparison with valsartan alone on a rat model of AD (aluminum-induced). The results showed that valsartan alone improved AD symptoms and did not increase the risk of developing AD, while the sacubitril/valsartan combination worsened the condition of the treated animals and increased their risk of developing AD [ 107 ].…”

Section: The Effects Of Ang II At1r Antagonists In Ad Pathologymentioning

confidence: 99%

Therapeutic Implications of Renin–Angiotensin System Modulators in Alzheimer’s Dementia

Ababei,

Bild,

Macadan

et al. 2023

Pharmaceutics

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The Renin–Angiotensin System (RAS) has attracted considerable interest beyond its traditional cardiovascular role due to emerging data indicating its potential involvement in neurodegenerative diseases, including Alzheimer’s dementia (AD). This review investigates the therapeutic implications of RAS modulators, specifically focusing on angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and renin inhibitors in AD. ACEIs, commonly used for hypertension, show promise in AD by reducing angiotensin (Ang) II levels. This reduction is significant as Ang II contributes to neuroinflammation, oxidative stress, and β-amyloid (Aβ) accumulation, all implicated in AD pathogenesis. ARBs, known for vasodilation, exhibit neuroprotection by blocking Ang II receptors, improving cerebral blood flow and cognitive decline in AD models. Renin inhibitors offer a novel approach by targeting the initial RAS step, displaying anti-inflammatory and antioxidant effects that mitigate AD degeneration. Preclinical studies demonstrate RAS regulation’s favorable impact on neuroinflammation, neuronal damage, cognitive function, and Aβ metabolism. Clinical trials on RAS modulators in AD are limited, but with promising results, ARBs being more effective that ACEIs in reducing cognitive decline. The varied roles of ACEIs, ARBs, and renin inhibitors in RAS modulation present a promising avenue for AD therapeutic intervention, requiring further research to potentially transform AD treatment strategies.

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