Nilvadipine antagonizes both Aβ vasoactivity in isolated arteries, and the reduced cerebral blood flow in APPsw transgenic mice

Paris, Daniel; Quadros, Amita; Humphrey, James; Patel, Nikunj; Crescentini, Robert M.; Crawford, Fiona; Mullan, Michael

doi:10.1016/j.brainres.2003.11.061

Cited by 70 publications

(42 citation statements)

References 35 publications

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“…We have shown previously that nilvadipine increases cerebral blood flow in a transgenic mouse model of AD (47). In addition, nilvadipine has been shown to improve spatial memory in a rat model of AD (48), consistent with our findings in transgenic mouse models of AD.…”

Section: Discussionsupporting

confidence: 91%

Selective Antihypertensive Dihydropyridines Lower Aβ Accumulation by Targeting both the Production and the Clearance of Aβ across the Blood-Brain Barrier

Paris

Bachmeier

Patel

et al. 2010

Mol Med

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102

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Section: Discussionsupporting

confidence: 91%

Selective Antihypertensive Dihydropyridines Lower Aβ Accumulation by Targeting both the Production and the Clearance of Aβ across the Blood-Brain Barrier

Paris

Bachmeier

Patel

et al. 2010

Mol Med

Self Cite

102

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“…Administration of nilvadipine reduced the levels of Aβ in the brain, likely by facilitating Aβ clearance, leading to improved learning and memory in mouse models of AD [100,101]. In addition to its effects on Aβ, nilvadipine restored Aβ-triggered reduction in cerebral blood flow in an AD mouse model [102], as well as in patients with early-stage AD [103,104]. Clinical investigations also showed that nilvadipine can prevent cognitive decline of patients with mild cognitive impairment [103,105].…”

Section: Antihypertensive Drugsmentioning

confidence: 99%

Drug Repositioning Approaches for the Discovery of New Therapeutics for Alzheimer's Disease

Kim

2015

Neurotherapeutics

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Summary Alzheimer's disease (AD) is the most common cause of dementia and represents one of the highest unmet needs in medicine today. Drug development efforts for AD have been encumbered by largely unsuccessful clinical trials in the last decade. Drug repositioning, a process of discovering a new therapeutic use for existing drugs or drug candidates, is an attractive and timely drug development strategy especially for AD. Compared with traditional de novo drug development, time and cost are reduced as the safety and pharmacokinetic properties of most repositioning candidates have already been determined. A majority of drug repositioning efforts for AD have been based on positive clinical or epidemiological observations or in vivo efficacy found in mouse models of AD. More systematic, multidisciplinary approaches will further facilitate drug repositioning for AD. Some experimental approaches include unbiased phenotypic screening using the library of available drug collections in physiologically relevant model systems (e.g. stem cell-derived neurons or glial cells), computational prediction and selection approaches that leverage the accumulating data resulting from RNA expression profiles, and genome-wide association studies. This review will summarize several notable strategies and representative examples of drug repositioning for AD.

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“…Among the dihydropyridine CCB tested, we identified nilvadipine for its ability to readily cross the BBB, to lower brain A␤ levels, to improve cognition, and to prevent cerebral blood flow deficits in a transgenic mouse model of AD overexpressing A␤ (18,20). Nilvadipine is a clinically used antihypertensive that we have shown to be well tolerated and to stabilize cognition in AD patients compared with untreated patients (21,22).…”

Section: Alzheimer Disease (Ad)mentioning

confidence: 99%

The Spleen Tyrosine Kinase (Syk) Regulates Alzheimer Amyloid-β Production and Tau Hyperphosphorylation

Paris

Ait‐Ghezala

Bachmeier

et al. 2014

Journal of Biological Chemistry

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Background: Spleen tyrosine kinase (Syk) mediates microglial activation and neurotoxicity elicited by Alzheimer A␤ peptides. Results: Syk regulates A␤ production via NFB-dependent mechanisms and Tau phosphorylation by controlling the activation of glycogen synthase 3␤. Conclusion: Inhibition of Syk can interrupt the neuroinflammation, pathological A␤ accumulation, and Tau hyperphosphorylation in AD. Significance: Syk represents a therapeutic target for the key pathological lesions that define AD.

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Nilvadipine antagonizes both Aβ vasoactivity in isolated arteries, and the reduced cerebral blood flow in APPsw transgenic mice

Cited by 70 publications

References 35 publications

Selective Antihypertensive Dihydropyridines Lower Aβ Accumulation by Targeting both the Production and the Clearance of Aβ across the Blood-Brain Barrier

Selective Antihypertensive Dihydropyridines Lower Aβ Accumulation by Targeting both the Production and the Clearance of Aβ across the Blood-Brain Barrier

Drug Repositioning Approaches for the Discovery of New Therapeutics for Alzheimer's Disease

The Spleen Tyrosine Kinase (Syk) Regulates Alzheimer Amyloid-β Production and Tau Hyperphosphorylation

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