Verapamil and Alzheimer’s Disease: Past, Present, and Future

Popović, Natalija; Morales-Delgado, Nicanor; Mena, David Vidal; Alonso, Antonia; Martínez, María Pascual; Bleda, María Caballero; Popovic, Marko

doi:10.3389/fphar.2020.00562

Cited by 23 publications

(8 citation statements)

References 146 publications

(151 reference statements)

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“…Other DHPs, such as nitrendipine and nilvadipine, have shown positive effects in delaying dementia onset [ 22 ] and slowing cognitive decline in people with mild cognitive impairment [ 49 ]. Verapamil, a phenylalkylamine class calcium channel blocker, has wide ranging cellular effects and improves cognition in rodent models, but its effects in AD are unclear (reviewed in [ 50 ]).…”

Section: Discussionmentioning

confidence: 99%

Oral nimodipine treatment has no effect on amyloid pathology or neuritic dystrophy in the 5XFAD mouse model of amyloidosis

et al. 2022

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Dysregulation of calcium homeostasis has been hypothesized to play a role in Alzheimer’s disease (AD) pathogenesis. Increased calcium levels can impair axonal transport, disrupt synaptic transmission, and ultimately lead to cell death. Given the potential role of calcium dyshomeostasis in AD, there is interest in testing the ability of already approved drugs targeting various calcium channels to affect amyloid pathology and other aspects of disease. The objective of this study was to test the effects of FDA-approved L-type calcium channel antagonist nimodipine on amyloid accumulation and dystrophic neurite formation in 5XFAD mice, a mouse model of amyloid pathology. 5XFAD transgenic mice and non-transgenic littermates were treated with vehicle or nimodipine-containing chow from two to eight months of age, then brains were harvested and amyloid pathology assessed by immunoblot and immunofluorescence microscopy analyses. Nimodipine was well tolerated and crossed the blood brain barrier, as expected, but there was no effect on Aβ accumulation or on the relative amount of neuritic dystrophy, as assessed by either immunoblot, dot blot or immunofluorescence imaging of Aβ42 and dystrophic neurite marker LAMP1. While we conclude that nimodipine treatment is not likely to improve amyloid pathology or decrease neuritic dystrophy in AD, it is worth noting that nimodipine did not worsen the phenotype suggesting its use is safe in AD patients.

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Section: Discussionmentioning

confidence: 99%

Oral nimodipine treatment has no effect on amyloid pathology or neuritic dystrophy in the 5XFAD mouse model of amyloidosis

et al. 2022

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“…According to the literature, a study introduced verapamil as a medication for male and female samples dealing with Alzheimer's disease [24]. According to a review study, verapamil, previously used for cardiovascular disease, is currently considered a treatment for neurological disorders [25]. In addition to Alzheimer's disease, verapamil is reported as a treatment in Huntington and Parkinson's diseases [26,27].…”

Section: Discussionmentioning

confidence: 99%

Drug Repurposing for Alzheimer’s Disease Based on Protein-Protein Interaction Network

Zakeri

Pashazadeh

MotieGhader

2021

BioMed Research International

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Alzheimer’s disease (AD) is known as a critical neurodegenerative disorder. It worsens as symptoms concerning dementia grow severe over the years. Due to the globalization of Alzheimer’s disease, its prevention and treatment are vital. This study proposes a method to extract substantial gene complexes and then introduces potential drugs in Alzheimer’s disease. To this end, a protein-protein interaction (PPI) network was utilized to extract five meaningful gene complexes functionally interconnected. An enrichment analysis to introduce the most important biological processes and pathways was accomplished on the obtained genes. The next step is extracting the drugs related to AD and introducing some new drugs which may be helpful for this disease. Finally, a complete network including all the genes associated with each gene complex group and genes’ target drug was illustrated. For validating the proposed potential drugs, Connectivity Map (CMAP) analysis was accomplished to determine target genes that are up- or downregulated by proposed drugs. Medical studies and publications were analyzed thoroughly to introduce AD-related drugs. This analysis proves the accuracy of the proposed method in this study. Then, new drugs were introduced that can be experimentally examined as future work. Raloxifene and gentian violet are two new drugs, which have not been introduced as AD-related drugs in previous scientific and medical studies, recommended by the method of this study. Besides the primary goal, five bipartite networks representing the genes of each group and their target miRNAs were constructed to introduce target miRNAs.

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“…According to the literature, a study introduced VERAPAMIL as medication for both male and female samples dealing with Alzheimer's disease(16). According to a review study, VERAPAMIL, previously used for cardiovascular disease, is currently considered as a treatment in neurological disorders (17). In addition to Alzheimer's disease, VERAPAMIL is reported as a treatment in Huntington and Parkinson's disease( 18), (19).…”

Section: Discussionmentioning

confidence: 99%

Drug Repurposing for Alzheimer’s Disease based on Protein-Protein Interaction Network

Zakeri

Pashazadeh

MotieGhader

2021

Preprint

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Background: Alzheimer's disease (AD) is known as a critical neurodegenerative disorder. It worsens as symptoms concerning dementia grow severe over the years. Due to the globalization of Alzheimer’s disease, its prevention and treatment is vital. This study proposes a method to extract substantial gene complexes and accomplish an enrichment analysis to introduce the most significant biological procedures. The next step is extracting the drugs related to AD and introduce some new drugs which may be useful for this disease. Results: To this end, protein-protein interactions (PPI) network was utilized to extract five meaningful gene complexes functionally interconnected. The next step was to construct a five bipartite network representing the genes of each group and their target miRNAs. Finally, a complete network including all the genes related to each gene complex group and genes’ target drug was illustrated. medical studies and publications were analyzed thoroughly to introduce AD-related drugs. Conclusions: This analysis proves the accuracy of the proposed method in this study. Then, new drugs were introduced that can be experimentally examined as future work. RALOXIFENE, GENTIAN VIOLET are two new drugs, which have not been introduced as AD-related drugs in previous scientific and medical studies, recommended by the method of this study. These two drugs.

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Verapamil and Alzheimer’s Disease: Past, Present, and Future

Cited by 23 publications

References 146 publications

Oral nimodipine treatment has no effect on amyloid pathology or neuritic dystrophy in the 5XFAD mouse model of amyloidosis

Oral nimodipine treatment has no effect on amyloid pathology or neuritic dystrophy in the 5XFAD mouse model of amyloidosis

Drug Repurposing for Alzheimer’s Disease Based on Protein-Protein Interaction Network

Drug Repurposing for Alzheimer’s Disease based on Protein-Protein Interaction Network

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