Pharmacotherapy of Alzheimer’s disease: an overview of systematic reviews

Majidazar, Reza; Rezazadeh-Gavgani, Erfan; Sadigh-Eteghad, Saeed; Naseri, Amirreza

doi:10.1007/s00228-022-03363-6

Cited by 32 publications

(17 citation statements)

References 115 publications

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“…People with AD have increased comorbidities [ 391 ] and increased medication use for both other neuropsychiatric conditions (such as depression, anxiety, psychosis, and opioid-treated pain) and some metabolic, endocrine, and neurological conditions (such as diabetes, hyperthyroidism, epilepsy, and Parkinson’s disease) [ 392 ]. Statins, antihypertensive drugs, antidiabetic agents, cerebrolysin, psychostimulants, and herbal medication seem to be effective in improving cognitive function in AD, but the evidence is limited [ 393 ]. A systematic review of the use of supplements did not show a reduction in the risk for cognitive decline [ 394 ].…”

Section: Alzheimer’s Drugsmentioning

confidence: 99%

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

Fišar

2022

Biomolecules

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Damage or loss of brain cells and impaired neurochemistry, neurogenesis, and synaptic and nonsynaptic plasticity of the brain lead to dementia in neurodegenerative diseases, such as Alzheimer’s disease (AD). Injury to synapses and neurons and accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles are considered the main morphological and neuropathological features of AD. Age, genetic and epigenetic factors, environmental stressors, and lifestyle contribute to the risk of AD onset and progression. These risk factors are associated with structural and functional changes in the brain, leading to cognitive decline. Biomarkers of AD reflect or cause specific changes in brain function, especially changes in pathways associated with neurotransmission, neuroinflammation, bioenergetics, apoptosis, and oxidative and nitrosative stress. Even in the initial stages, AD is associated with Aβ neurotoxicity, mitochondrial dysfunction, and tau neurotoxicity. The integrative amyloid-tau-mitochondrial hypothesis assumes that the primary cause of AD is the neurotoxicity of Aβ oligomers and tau oligomers, mitochondrial dysfunction, and their mutual synergy. For the development of new efficient AD drugs, targeting the elimination of neurotoxicity, mutual potentiation of effects, and unwanted protein interactions of risk factors and biomarkers (mainly Aβ oligomers, tau oligomers, and mitochondrial dysfunction) in the early stage of the disease seems promising.

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Section: Alzheimer’s Drugsmentioning

confidence: 99%

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

Fišar

2022

Biomolecules

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“…Moreover, based on the analysis of kinetic inhibition, pH-dependence, and L-carnitine sensitivity, the amantadine transport system is likely to be different from other putative cation transport systems of the inner BRB, which transport verapamil, clonidine, and propranolol [ 3 , 4 , 5 ]. Adamantane derivatives, such as amantadine and memantine, are known to exert neuroprotective effects by inhibiting N-methyl-D-aspartate (NMDA) receptors [ 6 , 7 , 8 , 9 ] and are used for the treatment of neurodegenerative disorders of the brain [ 10 , 11 , 12 , 13 ]. Previous studies showed that the overactivation of NMDA receptors caused damage to retinal ganglion cells [ 14 , 15 , 16 ] and it is considered a mechanism of retinal neurodegeneration under pathological conditions, such as glaucoma [ 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

The Structural Characteristics of Compounds Interacting with the Amantadine-Sensitive Drug Transport System at the Inner Blood–Retinal Barrier

et al. 2023

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Blood-to-retina transport across the inner blood–retinal barrier (BRB) is a key determinant of retinal drug concentration and pharmacological effect. Recently, we reported on the amantadine-sensitive drug transport system, which is different from well-characterized transporters, at the inner BRB. Since amantadine and its derivatives exhibit neuroprotective effects, it is expected that a detailed understanding of this transport system would lead to the efficient retinal delivery of these potential neuroprotective agents for the treatment of retinal diseases. The objective of this study was to characterize the structural features of compounds for the amantadine-sensitive transport system. Inhibition analysis conducted on a rat inner BRB model cell line indicated that the transport system strongly interacts with lipophilic amines, especially primary amines. In addition, lipophilic primary amines that have polar groups, such as hydroxy and carboxy groups, did not inhibit the amantadine transport system. Furthermore, certain types of primary amines with an adamantane skeleton or linear alkyl chain exhibited a competitive inhibition of amantadine uptake, suggesting that these compounds are potential substrates for the amantadine-sensitive drug transport system at the inner BRB. These results are helpful for producing the appropriate drug design to improve the blood-to-retina delivery of neuroprotective drugs.

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“…From a pathological perspective, AD is defined by the presence of plaques of amyloid-beta (Aβ) peptides (derived from the proteolytic cleavage of the amyloid precursor protein) and neurofibrillary tangles (produced by hyperphosphorylated tau protein forms) [ 3 ]. Currently, there is no disease-modifying therapy capable of reversing AD [ 4 ], but there are treatments that may improve cognitive and behavioral symptoms [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Circulating long non-coding RNAs as novel diagnostic biomarkers for Alzheimer’s disease (AD): A systematic review and meta-analysis

et al. 2023

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Background Long non-coding RNAs (lncRNAs) have been reported to be involved in the pathogenesis of neurodegenerative diseases. It has also been hypothesized that plasma exosomal lncRNAs may be used as Alzheimer’s disease (AD) biomarkers. In this systematic review, we compiled all studies on the subject to evaluate the accuracy of lncRNAs in identifying AD cases through meta-analysis. Methods A PRISMA-compliant systematic search was conducted in PubMed/MEDLINE, EMBASE, and Web of Science databases for English publications till September 2022. We included all observational studies published which investigated the sensitivity and specificity of various lncRNAs in plasma samples of AD diagnosis. Our search strategy included lncRNA and all the related spelling and abbreviation variations combined with the keyword Alzheimer’s disease. Methodological quality was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines and the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-II) tool. The meta-analysis was carried out using the area under the Receiver Operator Characteristic (ROC) curves (AUC) and sensitivity and specificity values to assess the accuracy of the identified lncRNAs in AD diagnosis. To account for the predicted heterogeneity of the study, a random-effects model was used. All the statistical analyses and visualizations were conducted using Stata 17.0 software. Results A total of seven studies (AD patients = 553, healthy controls = 513) were included in the meta-analysis. Three lncRNAs were upregulated (RNA BACE-AS1, RNA NEAT1, RNA GAS5), and one lncRNA (MALAT1) was downregulated in plasma samples of AD patients. RNA 51A and RNA BC200 were reported to have variable expression patterns. A lncRNA (RNA 17A) was not significantly different between AD and control groups. The pooled sensitivity, specificity, and AUC values of lncRNAs in identifying AD were (0.74; 95% CI [0.63, 0.82], I2 = 79.2%), (0.88; 95% CI [0.75, 0.94], I2 = 88.9%), and 0.86; 95% CI [0.82, 0.88], respectively. In addition, the pooled diagnostic odds ratio (DOR) of the five individual lncRNAs in AD diagnosis was 20. Conclusion lncRNAs had high accuracy in identifying AD and must be seen as a promising diagnostic biomarker of the disease.

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Pharmacotherapy of Alzheimer’s disease: an overview of systematic reviews

Cited by 32 publications

References 115 publications

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

The Structural Characteristics of Compounds Interacting with the Amantadine-Sensitive Drug Transport System at the Inner Blood–Retinal Barrier

Circulating long non-coding RNAs as novel diagnostic biomarkers for Alzheimer’s disease (AD): A systematic review and meta-analysis

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