The natural β-carboline alkaloids display similarities with neurotransmitters that can be favorably exploited to design bioactive and bioavailable drugs for Alzheimer's disease (AD) therapy. Several AD targets are currently and intensively being investigated, divided in different hypotheses: mainly the cholinergic, the amyloid β (Aβ), and the Tau hypotheses. To date, only symptomatic treatments are available involving acetylcholinesterase and NMDA inhibitors. On the basis of plethoric single-target structure−activity relationship studies, the β-carboline scaffold was identified as a powerful tool for fostering activity and molecular interactions with a wide range of AD-related targets. This knowledge can undoubtedly be used to design multitarget-directed ligands, a highly relevant strategy preferred in the context of multifactorial pathology with intricate etiology such as AD. In this review, we first individually discuss the AD targets of the β-carbolines, and then we focus on the multitarget strategies dedicated to the deliberate design of new efficient scaffolds.
IntroductionMetabolic syndrome and other cardiovascular risk factors are highly prevalent in people with mental severe illness (Sun & Jang, 2020).Metabolic disorders in people with schizophrenia increase their risk of developing cardiovascular disease, consequently reducing their life expectancy by approximately 10 to 25 years (Heald et al., 2017)In part these cardio-metabolic risk factors are attributable to unhealthy lifestyle, including poor diet and sedentary behaviour.Lifestyle interventions (diet, increased physical activity) are the first-line treatments to decrease that risk.ObjectivesOur objective is to carry out a prospective study on the application of a program of healthy habits in outpatients unitMethodsPatients with mental severe illness were recruited at a mental health center in the Hospital Clinic of Valencia. Inclusion criteria: age from 18 to 65 years and diagnosis of severe/persistent mental illness Exclusion criteria: acute illness, were not understanding Spanish, not be able to read and understand questionnaries. We included following data: sociodemographic data and aspects of the health behaviors, anthropometric measurements and analytical with hemogram and biochemistry pre and post-intervention. All subjects gave informed consent for participation in the study.ResultsWe included 12 patients, but only 9 completed the full program. Average baseline data suggests that participants were at increased health risk when entering the program.At the end of the program, differences were observed: a reduction in glucose profile, a reduction of an average of 3.33 kg from the initial weight and a reduction of 10 points in blood pressure.ConclusionsThis real world pilot trial evaluate of a health promotion intervention targeting physical activity and healthy eating in mental health care using a specific programme.Disclosure of InterestNone Declared
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