Opportunities for Drug Repurposing of Serotonin Reuptake Inhibitors: Potential Uses in Inflammation, Infection, Cancer, Neuroprotection, and Alzheimer’s Disease Prevention

2021 ◽  
Author(s):  
Madeline J. Nykamp ◽  
Charles F. Zorumski ◽  
Angela M. Reiersen ◽  
Ginger E. Nicol ◽  
John Cirrito ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Serotonin Reuptake ◽  
Depressive Disorders ◽  
Drug Repurposing ◽  
Serotonin Reuptake Inhibitors ◽  
Neuroprotective Activity ◽  
Current Evidence ◽  
Ongoing Research ◽  
Neoplastic Processes

AbstractSerotonin reuptake inhibitors (SRIs) are safe and widely used for a variety of indications including depressive disorders, anxiety, and chronic pain. Besides inhibiting the serotonin transporter, these medications have broad-spectrum properties in many systems. Their roles have been studied in cancer, Alzheimer’s disease, and infectious processes. The COVID-19 pandemic highlighted the importance of drug repurposing of medications already in use. We conducted a narrative review of current evidence and ongoing research on drug repurposing of SRIs, with a focus on immunomodulatory, antiproliferative, and neuroprotective activity. SRIs may have clinical use as repurposed agents for a wide variety of conditions including but not limited to COVID-19, Alzheimer’s disease, and neoplastic processes. Further research, particularly randomized controlled trials, will be necessary to confirm the utility of SRIs for new indications.

Multi-functional neuroprotective activity of neohesperidin dihydrochalcone: a novel scaffold for Alzheimer's disease therapeutics identified via drug repurposing screening

2018 ◽  
Vol 42 (14) ◽  
pp. 11755-11769 ◽  
Author(s):  
Sandipan Chakraborty ◽  
Jyotirmoy Rakshit ◽  
Jaya Bandyopadhyay ◽  
Soumalee Basu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Antioxidant Activity ◽  
Drug Repurposing ◽  
Neuroprotective Activity ◽  
Amyloid Aggregation ◽  
Aggregation Inhibition ◽  
Target Screening ◽  
Novel Scaffold

Multi-target screening identifies neohesperidin dihydrochalcone for Alzheimer's disease therapeutics, which exhibits strong BACE1 and amyloid aggregation inhibition along with antioxidant activity.

Selective Serotonin Reuptake Inhibitors and Trazodone for Treatment of Depression, Psychosis, and Behavioral Symptoms in Patients With Dementia

2000 ◽  
Vol 12 (S1) ◽  
pp. 245-251 ◽  
Author(s):  
David L. Sultzer
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Effects ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Serotonin Reuptake Inhibitors ◽  
Behavioral Symptoms ◽  
Selective Serotonin ◽  
Clinical Aspects ◽  
Treatment Of Depression

Depression, psychosis, agitation, and aggression are fundamental clinical aspects of Alzheimer's disease (AD) and other dementia syndromes. Although behavioral, environmental, and pharmacologic interventions often help ameliorate these symptoms, the efficacy of specific interventions is uncertain, and adverse effects of medications are common.

scholarly journals Nutrition-Based Approaches in Clinical Trials Targeting Cognitive Function: Highlights of the CTAD 2020

2021 ◽  
pp. 1-5
Author(s):  
K.V. Giudici
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Function ◽  
Healthy Aging ◽  
Current Evidence ◽  
Omega 3 ◽  
Duration Of Treatment ◽  
Ongoing Research ◽  
Positive Effects

The Clinical Trials on Alzheimer’s Disease (CTAD) 2020 conference was the stage for researchers from all over the world to present their recent and ongoing research focused on potential Alzheimer’s disease (AD) treatments and prevention of cognitive decline. Among a varied range of topics, nutritional aspects arose as possibilities of treatments towards the promotion of a healthy aging. Among the discussed themes, supplementation of omega-3 polyunsaturated fatty acids and multi-nutrient approaches were presented, suggesting that long-term supplementation (i.e., over 3 years) might be needed for observing positive effects on cognitive performance. Trials testing ketogenic agents and carbohydrate-restricted diet were also presented and showed promising effects on improving cognitive function of mild-cognitive impaired (MCI) and pre-diabetic individuals, respectively, in a short-term way (i.e. after 3 to 6 months). The combination of some of the nutritional approaches with physical activity interventions raises the question on whether they would individually perform in a similar way. Promising therapies involving nutrition appear to be safe and well tolerated by volunteers. Failures on achieving positive findings raise questions on whether they were driven by specific characteristics of the studied populations, insufficient doses or duration of treatment. Notwithstanding, current evidence on the applicability of nutrition-based approaches as AD treatments are encouraging but demand further research on the topic.

Modulation of Inflammation as a Way of Delaying Alzheimer's Disease Progression: The Diet's Role

2018 ◽  
Vol 15 (4) ◽  
pp. 363-380 ◽  
Author(s):  
R. Businaro ◽  
M. Corsi ◽  
R. Asprino ◽  
C. Di Lorenzo ◽  
D. Laskin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Food Sources ◽  
Neuroprotective Activity ◽  
Current Evidence ◽  
Low Grade ◽  
Microglia Polarization ◽  
Inflammatory Phenotype ◽  
As Stress ◽  
Dietary Bioactive Compounds

Background: Most of the recent reports suggest that inflammatory mediators play a central role in the etiopathogenesis of Alzheimer's disease (AD) and that the conditions leading to a chronic low-grade inflammation, such as stress, depression, obesity and metabolic syndrome, increase the odds of developing Mild Cognitive Impairment (MCI) and AD. Microglia cells are the main actors in the AD process: stimuli from the microenvironment may induce microglia cells to switch to a classically activated inflammatory phenotype M1, or, on the contrary to an alternatively activated M2 phenotype characterized by the secretion of different types of cytokines. Many attempts are currently being made in order to delay the progression of AD by reducing inflammatory mechanisms underlying the disease. Several studies support a relationship among neuroinflammation and nutrients, foods or dietary patterns, taking into account the synergistic or antagonistic biochemical interactions among nutrients as well as the different food sources of the same nutrient. Natural antioxidant and anti-inflammatory compounds found in plant foods, such as fruits, particularly berries (such as strawberry, blueberry, blackcurrant, blackberry, blueberry and mulberry) have been shown to exert neuroprotective activity. It is still unclear whether the dietary bioactive compounds enter the Blood Brain Barrier (BBB) playing a direct antiinflammatory or pro-inflammatory effect on microglia and/or other Central Nervous System (CNS) cells. Another hypothesis is that they may trigger a peripheral reaction that induce indirectly a CNS' response. The subsequent synthesis of cytokines may drive microglia polarization by different ways. So, via an indirect route microglia detects and responds to immune-to-brain signaling. Conclusion: This review summarizes current evidence about the potential mechanisms of the interaction among diet, neuroinflammation and AD.

Effect of Selective Serotonin Reuptake Inhibitors in Alzheimer’s Disease with Comorbid Depression

Drugs & Aging ◽  
2012 ◽  
Vol 29 (10) ◽  
pp. 793-806 ◽  
Author(s):  
Amir A. Sepehry ◽  
Philip E. Lee ◽  
Ging Yuek R. Hsiung ◽  
B. Lynn Beattie ◽  
Claudia Jacova
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Serotonin Reuptake Inhibitors ◽  
Selective Serotonin ◽  
Comorbid Depression

scholarly journals REVIEW ON EVALUATING THE ROLE OF NSAIDS FOR THE TREATMENT OF ALZHEIMER'S DISEASE

2021 ◽  
pp. 91-94
Author(s):  
KRISHNENDU P. R. ◽  
ARJUN B. ◽  
VIBINA K. ◽  
NIVEA CLEO T. S. ◽  
DRISYA N. K. ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorders ◽  
Symptomatic Relief ◽  
Drug Repurposing ◽  
Epidemiological Studies ◽  
Neuroprotective Activity ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
The Cost

Recently, several studies have been reported that nonsteroidal anti-inflammatory drugs can fight against neurodegenerative disorders by various mechanisms. Currently, available therapies of neurodegenerative disorders (NDs) provide only symptomatic relief. This is the point at which we need an alternative that acts on the root cause of disease. Parkinson’s disease and Alzheimer’s disease are the two NDs concentrated here. Since the drug profile is already known, drug repurposing is a promising technique in research, thereby reducing the cost and period effectively. Epidemiological studies on various nonsteroidal anti-inflammatory drugs (NSAIDs) showed good results, but when it came to clinical studies the results are found to be poor. Hence, it can be concluded that NSAIDs provide its neuroprotective activity on its long-term use only, as the brain accessibility of this kind of drug is poor due to its lower lipophilicity.

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