, Current Opinion in Chemical Biology, Volume 65, December 2021
Drug repurposing aims to find new uses for already existing and approved drugs. We now provide a brief overview of recent developments in drug repurposing using machine learning alongside other computational approaches for comparison. We also highlight several applications for cancer using kinase inhibitors, Alzheimer's disease as well as COVID-19.
, Prostaglandins and Other Lipid Mediators, Volume 156, October 2021
Millions of people are affected by neurodegenerative diseases worldwide. They occur due to the loss of brain functions or peripheral nervous system dysfunction. If untreated, prolonged condition ultimately leads to death. Mostly they are associated with stress, altered cholesterol metabolism, inﬂammation and organelle dysfunction. Endogenous cholesterol and phospholipids in brain undergo auto-oxidation by enzymatic as well as non-enzymatic modes leading to the formation of by-products such as 4-hydroxynonenal and oxysterols.
, Bioorganic and Medicinal Chemistry Letters, Volume 49, 1 October 2021
Despite the better understanding of the mechanisms underlying Alzheimer's Disease (AD) and launched clinical trials, no AD-modifying treatment based on a synthetic drug has been introduced for almost twenty years. The serotonin 5-HT6 and 5-HT7 receptors turned out to be promising biological targets for modulation of central nervous system dysfunctions including cognitive impairment. Within this paper, we evaluate the pharmacological potency of both, 5-HT6R and 5-HT7R, agents in search for novel AD treatment.
, Ageing Research Reviews, Volume 70, September 2021
The novel coronavirus disease 2019 (COVID-19) has pushed the medical system to its breaking point. While the virus does not discriminate, the elderly and those with comorbidities, including hypertension severe obesity, diabetes mellitus, coronary disease, pneumonia and dementia, are at a greater risk for adverse outcomes due to COVID-19. While many people navigate their new normal, the question of what the long-lasting effects of the pandemic may be, lingers.
, Behavioural Brain Research, Volume 414, 24 September 2021
Rho-associated coiled-coil kinase (ROCK), a serine/threonine kinase regulated by the small GTPase RhoA, is involved in regulating cell migration, proliferation, and survival. Numerous studies have shown that the RhoA/ROCK signaling pathway can promote Alzheimer's disease (AD) occurrence. ROCK activation increases β-secretase activity and promotes amyloid-beta (Aβ) production; moreover, Aβ further activates ROCK. This is suggestive of a possible positive feedback role for Aβ and ROCK. Moreover, ROCK activation promotes the formation of neurofibrillary tangles and abnormal synaptic contraction.
, Neurobiology of Disease, Volume 156, August 2021
Sporadic late-onset Alzheimer's disease (AD) is the most frequent cause of dementia associated with aging. Due to the progressive aging of the population, AD is becoming a healthcare burden of unprecedented proportions. Twenty years ago, it was reported that some indole molecules produced by the gut microbiota possess essential biological activities, including neuroprotection and antioxidant properties. Since then, research has cemented additional characteristics of these substances, including anti-inflammatory, immunoregulatory, and amyloid anti-aggregation features.
, Neurochemistry International, Volume 147, July 2021
Alzheimer's disease (AD) is by far the most prevalent neurodegenerative disease of aging and is a major burden for patients, caregivers, and the overall health care system. The complexity of AD pathophysiology and the lack of deep understanding of disease mechanisms impeded the development of AD therapy. Currently approved treatments for AD only modestly improve cognitive function but do not modify disease course. The lack of pharmacological approaches has led to the consideration of alternative strategies to prevent or to slow down the progression of AD.
, Progress in Retinal and Eye Research, Volume 82, May 2021
Alzheimer's Disease (AD) is a devastating neurodegenerative disorder of the brain, clinically characterised by cognitive deficits that gradually worsen over time. There is, at present, no established cure, or disease-modifying treatments for AD. As life expectancy increases globally, the number of individuals suffering from the disease is projected to increase substantially. Cumulative evidence indicates that AD neuropathological process is initiated several years, if not decades, before clinical signs are evident in patients, and diagnosis made.
, EBioMedicine, Volume 67, May 2021
Background: The pathological changes in Alzheimer's Disease (AD) and other neurodegenerative disorders begin decades prior to their clinical expression. However, the clinical diagnosis of neurodegenerative dementias is not straightforward. Lactoferrin is an iron-binding, antimicrobial glycoprotein with a plethora of functions, including acting as an important immune modulator and by having a bacteriocidic effect. Two previous studies indicated that salivary lactoferrin could differentiate between neurodegenerative dementias.
, The Lancet Public Health, Volume 6, March 2021
Background: The population of older adults (ie, those aged ≥55 years) in England is becoming increasingly ethnically diverse. Previous reports indicate that ethnic inequalities in health exist among older adults, but information is limited by the paucity of data from small minority ethnic groups. This study aimed to analyse inequalities in health-related quality of life (HRQoL) and five determinants of health in older adults across all ethnic groups in England.