Abstract:
:Late-life depression is associated with significant cognitive impairment. Meta-analyses showed that depression is associated with an increased risk for Alzheimer's disease (AD) and it might be an etiological factor for AD. Since late-life depression is often connected with cognitive impairment and dementia is usually associated with depressive symptoms, a simple diagnostic approach to distinguish between the disorders is challenging. Several overlapping pathophysiological substrates might explain the comorbidity of both syndromes. Firstly, a stress syndrome, i.e., elevated cortisol levels, has been observed in up to 70% of depressed patients and also in AD pathology. Stress conditions can cause hippocampal neuronal damage as well as cognitive impairment. Secondly, the development of a depression and dementia after the onset of vascular diseases, the profile of cerebrovascular risk factors in both disorders and the impairments depending on the location of cerebrovascular lesions, speak in favor of a vascular hypothesis as a common factor for both disorders. Thirdly, neuroinflammatory processes play a key role in the etiology of depression as well as in dementia. Increased activation of microglia, changes in Transforming-Growth-Factor beta1 (TGF-beta1) signaling, production of pro-inflammatory cytokines as well as reduction of anti-inflammatory molecules are examples of common pathways impaired in dementia and depression. Fourthly, the neurotrophin BDNF is highly expressed in the central nervous system, especially in the hippocampus, where it plays a key role in the proliferation, differentiation and the maintenance of neuronal integrity throughout lifespan. It has been associated not only with antidepressant properties but also a reduction of cognitive impairment and therefore could be involved also in AD. Another etiologic factor is amyloid accumulation, as plasma amyloid beta-42 independently predicts both late-onset depression and AD. Higher plasma amyloid beta-42 predicts the development of late onset depression and conversion to possible AD. However, clinical trials with antibodies against beta amyloid recently failed, i.e., Solanezumab, Aducanumab, and Crenezumab. An overproduction of amyloid-beta might simply reflect a form of synaptic plasticity to compensate for neuronal dysfunction in different kind of neurological and psychiatric diseases of multiple etiologies. The tau hypothesis, sex/gender specific differences, epigenetics and the gut microbiota-brain axis imply other potential common pathways connecting late-life depression and dementia. In conclusion, different potential pathophysiological links between dementia and depression highlight several specific synergistic and multifaceted treatment possibilities, depending on the individual risk profile of the patient.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Linnemann C,Lang UEdoi
10.3389/fphar.2020.00279subject
Has Abstractpub_date
2020-03-13 00:00:00pages
279issn
1663-9812journal_volume
11pub_type
杂志文章,评审abstract:Introduction:Infliximab (IFX) was the first anti-tumor necrosis factor (TNFα) antibody to be used in the treatment of severe chronic inflammatory diseases, such as Crohn's disease and rheumatoid arthritis. A number of serious adverse drug reactions are known to be associated with IFX use; they include infections, malig...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00513
更新日期:2020-04-22 00:00:00
abstract::Immune checkpoint inhibitors (ICIs) that target cytotoxic T lymphocyte antigen 4, programmed cell death-1, and PD-ligand 1 have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. ICIs are increasingly being used in early cancer settings and in combination with various other typ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.01350
更新日期:2019-11-29 00:00:00
abstract::Diabetes is affecting the social and economic developments in developing countries like Sri Lanka. Siddha Medicine (Tamil Medicine) is mostly practiced in the Eastern and Northern Provinces of Sri Lanka. Our recent review of Sri Lankan Siddha historical documents identified 171 plant species used to prepare anti-diabe...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01022
更新日期:2018-10-10 00:00:00
abstract:BACKGROUND:Previous studies compared the molecular similarity of marketed drugs and endogenous human metabolites (endogenites), using a series of fingerprint-type encodings, variously ranked and clustered using the Tanimoto (Jaccard) similarity coefficient (TS). Because this gives equal weight to all parts of the encod...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00266
更新日期:2016-08-22 00:00:00
abstract::Sigma-1 receptors (S1R) and sigma-2 receptors (S2R) may modulate nociception without the liabilities of opioids, offering a promising therapeutic target to treat pain. The purpose of this study was to investigate the in vivo analgesic and anti-allodynic activity of two novel sigma receptor antagonists, the S1R-selecti...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00678
更新日期:2019-06-14 00:00:00
abstract::Natural products (NPs) are an important source for new drug discovery over the past decades, which have been demonstrated to be effectively used in cancer prevention, treatment, and adjuvant therapy. Many methods, such as the genomic and metabolomic approaches, immunochemistry, mass spectrometry, and chromatography, h...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.01438
更新日期:2019-11-28 00:00:00
abstract::Objectives: The aim of this study is to conduct an analysis on the regulation and application of managed entry agreements (MEA) for oncology drugs across different European countries. Methods: Literature search and document analysis were performed between September 2015 and June 2016 to collect information on the regu...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00171
更新日期:2017-04-04 00:00:00
abstract::Background: Rheumatoid arthritis is a type of systemic and complex autoimmune other disease characterized by chronic joint inflammation. Spleen tyrosine kinase (Syk) inhibitors are regarded as an effective alternative to existing drugs for the treatment of this disease. However, studies evaluating fostamatinib, a new ...
journal_title:Frontiers in pharmacology
pub_type:
doi:10.3389/fphar.2019.00897
更新日期:2019-08-14 00:00:00
abstract::Intestinal barrier dysfunction is an important clinical problem in various acute and chronic pathological conditions. Ferulic acid (FA) can attenuate the intestinal epithelial barrier dysfunction, however, the underlying mechanism remains unclear. The present study aimed to uncover the protective effect of FA on intes...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00376
更新日期:2020-04-03 00:00:00
abstract:PURPOSE:Colostrum has been proposed to treat severe dryness and problematic eye lesions showing a beneficial effect. The aim of the study was to investigate the effect of 2-fucosyl-lactose, a natural sugar present in the human colostrum, in an experimental dry eye. METHODS:Dry eye was induced in adult male New Zealand...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2015.00280
更新日期:2015-11-18 00:00:00
abstract::The number of colorectal cancer (CRC) cases have increased gradually year by year. In fact, CRC is one of the most widely diagnosed cancer in men and women today. This disease is usually diagnosed at a later stage of the development, and by then, the chance of survival has declined significantly. Even though substanti...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2017.00583
更新日期:2017-08-28 00:00:00
abstract::Background: Modeling and simulation is increasingly used to study pediatric pharmacokinetics, but clinical implementation of age-appropriate doses lags behind. Therefore, we aimed to develop model-informed doses using published pharmacokinetic data and a decision framework to adjust dosing guidelines based on these do...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.592204
更新日期:2020-12-16 00:00:00
abstract::In spite of recent therapeutic advances, multiple myeloma (MM) remains a malignancy with very low curability. This has been partly attributed to the existence of a drug-resistant subpopulation known as cancer stem cells (CSCs). MM-CSCs are equipped with the necessary tools that render them highly resistant to virtuall...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00610
更新日期:2017-09-08 00:00:00
abstract:Introduction:Diabetes is a metabolic disease with a high incidence and serious harm to human health. Islet β-cell function defects can occur in the late stage of type 1 diabetes and type 2 diabetes. Studies have shown that stem cell is a promising new approach in bioengineering regenerative medicine. In the study of st...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01576
更新日期:2020-01-24 00:00:00
abstract::Corticotrophin releasing factor (CRF) and its related peptides differentially bind to CRF receptors to modulate stress-related behaviors. CRF receptors comprise two G-protein coupled receptors (GPCR), type-1 CRF receptors (CRF1), and type-2 CRF receptors (CRF2). CRF2 encompasses three spliced variants in humans, alpha...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01501
更新日期:2020-01-08 00:00:00
abstract::Uterine leiomyomas are the most common benign neoplasms in women of reproductive age. However, non-surgical treatments for uterine myomas have not been fully evaluated. In Korea and China, Gyejibongnyeong-hwan (GBH) is widely used to treat gynecological diseases. Thus, we investigated the effects of GBH in human uteri...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01105
更新日期:2019-09-25 00:00:00
abstract::Many current chemotherapies function by damaging genomic DNA in rapidly dividing cells ultimately leading to cell death. This therapeutic approach differentially targets cancer cells that generally display rapid cell division compared to normal tissue cells. However, although these treatments are initially effective i...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2013.00005
更新日期:2013-01-31 00:00:00
abstract::In human uveal melanoma (UM), tumor enlargement is associated with increases in aqueous humor vascular endothelial growth factor-A (VEGF-A) content that induce neovascularization. 3-Iodothyronamine (3-T1AM), an endogenous thyroid hormone metabolite, activates TRP melastatin 8 (TRPM8), which blunts TRP vanilloid 1 (TRP...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01234
更新日期:2018-11-13 00:00:00
abstract::Rapidly progressive interstitial lung disease is typically associated with clinically amyopathic dermatomyositis and the anti-melanoma differentiation associated gene 5 antibody, a condition with high mortality and resistance to classic immunosuppression. Recent reports have described the efficacy of the Janus kinase ...
journal_title:Frontiers in pharmacology
pub_type:
doi:10.3389/fphar.2020.585761
更新日期:2020-12-15 00:00:00
abstract::Objective: This research aimed to validate the therapeutic effect of losmapimod and explore the underlying mechanism in its treatment of epilepsy. Methods: A rat model of epilepsy was constructed with an injection of pilocarpine. Microarray analysis was performed to screen aberrantly expressed mRNAs and activated sign...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00625
更新日期:2019-06-07 00:00:00
abstract::Fibrosis is a major player in cardiovascular disease, both as a contributor to the development of disease, as well as a post-injury response that drives progression. Despite the identification of many mechanisms responsible for cardiovascular fibrosis, to date no treatments have emerged that have effectively reduced t...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2017.00318
更新日期:2017-05-31 00:00:00
abstract::Background: Sorafenib (Nexavar®) is an FDA-approved systemic therapy for advanced hepatocellular carcinoma (HCC). However, the low efficacy and adverse effects at high doses limit the clinical application of sorafenib and strongly recommend its combination with other agents aiming at ameliorating its drawbacks. OSU-2S...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00463
更新日期:2016-11-30 00:00:00
abstract::Hepatosteatosis (HS), a clinical feature of fatty liver with the excessive intracellular accumulation of triglyceride in hepatocytes, is manifested by perturbation of the maintenance of liver lipid homeostasis. Samjunghwan (SJH) is an herbal formula used mostly in Korean traditional medicine that is effective against ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00596
更新日期:2018-06-19 00:00:00
abstract::Due to our interest in the chemical space of organic dyes to identify potential small-molecule inhibitors (SMIs) for protein-protein interactions (PPIs), we initiated a screen of such compounds to assess their inhibitory activity against the interaction between SARS-CoV-2 spike protein and its cognate receptor ACE2, w...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.600372
更新日期:2021-01-13 00:00:00
abstract::Excessive cerebral inflammation plays a key role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Berberine, an isoquinoline alkaloid isolated from Chinese herb Coptis chinensis, possesses anti-inflammatory, and neuroprotective effects. Here we evaluated the beneficial effects of berberine against SAH-...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.01073
更新日期:2020-07-10 00:00:00
abstract::Drug-induced liver injury (DILI) is a major clinical problem where natural compounds hold promise for its abrogation. Khaya grandifoliola (Meliaceae) is used in Cameroonian traditional medicine for the treatment of liver related diseases and has been studied for its hepatoprotective properties. Till date, reports show...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00653
更新日期:2017-09-19 00:00:00
abstract::In studies comparing regular versus on-demand treatment for patients with mild persistent asthma, on-demand treatment seems to have a similar efficacy on clinical and functional outcomes, but it does not suppress chronic airway inflammation or airway hyper-responsiveness (AHR) associated with asthma. Data on the effic...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2011.00035
更新日期:2011-07-14 00:00:00
abstract::A growing set of observations points to mitochondrial dysfunction, iron accumulation, oxidative damage and chronic inflammation as common pathognomonic signs of a number of neurodegenerative diseases that includes Alzheimer's disease, Huntington disease, amyotrophic lateral sclerosis, Friedrich's ataxia and Parkinson'...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2014.00038
更新日期:2014-03-10 00:00:00
abstract::Skeletal dysplasias represent a large and diverse group of rare conditions affecting collagen and bone. They can be clinically classified based on radiographic and physical features, and many can be further defined at a molecular level (Bonafe et al., 2015). Early diagnosis is critical to proper medical management inc...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2017.00079
更新日期:2017-03-06 00:00:00
abstract::Pasteurella multocida (PM) can invade the upper respiratory tract of the body and cause death and high morbidity. Tildipirosin, a new 16-membered-ring macrolide antimicrobial, has been recommended for the treatment of respiratory diseases. The objective of this research was to improve the dose regimes of tildipirosin ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00765
更新日期:2018-07-26 00:00:00