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- Graham, WV, et al.
(författare)
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Update on Alzheimer's Disease Therapy and Prevention Strategies
- 2017
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Ingår i: Annual review of medicine. - : Annual Reviews. - 1545-326X .- 0066-4219. ; 68, s. 413-430
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is the primary cause of age-related dementia. Effective strategies to prevent and treat AD remain elusive despite major efforts to understand its basic biology and clinical pathophysiology. Significant investments in therapeutic drug discovery programs over the past two decades have yielded some important insights but no blockbuster drugs to alter the course of disease. Because significant memory loss and cognitive decline are associated with neuron death and loss of gray matter, especially in the frontal cortex and hippocampus, some focus in drug development has shifted to early prevention of cellular pathology. Although clinical trial design is challenging, due in part to a lack of robust biomarkers with predictive value, some optimism has come from the identification and study of inherited forms of early-onset AD and genetic risk factors that provide insights about molecular pathophysiology and potential drug targets. In addition, better understanding of the Aβ amyloid pathway and the tau pathway—leading to amyloid plaques and neurofibrillary tangles, respectively, which are histopathological hallmarks of AD—continues to drive significant drug research and development programs. The main focus of this review is to summarize the most recent basic biology, biochemistry, and pharmacology that serve as a foundation for more than 50 active advanced-phase clinical trials for AD prevention and therapy.
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- Maegdefessel, L, et al.
(författare)
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Pathogenesis of abdominal aortic aneurysms: microRNAs, proteases, genetic associations
- 2014
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Ingår i: Annual review of medicine. - : Annual Reviews. - 1545-326X .- 0066-4219. ; 65, s. 49-62
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Tidskriftsartikel (refereegranskat)abstract
- Abdominal aortic aneurysm (AAA) disease is a common, morbid, and highly lethal pathology. Extraordinary efforts have been launched to determine the molecular and pathophysiological characteristics of AAAs. Although surgery is highly effective in preventing death by rupture for larger AAAs, no guidance or preventive therapy is currently available for the >90% of patients whose aneurysms are below the surgical threshold. Predictive animal models of AAA as well as human pathological samples have revealed a complex circuit of AAA formation and progression. The proteolytic destruction of matrix components of the aorta by different proteases has been extensively studied over many years. Recently, a novel class of small noncoding RNAs, called microRNAs, was identified as “fine-tuners” of the translational output of target genes; they act by promoting mRNA degradation. Their therapeutic potential in limiting AAA development appears very intriguing. Further, current studies assessing genetic and heritable associations for AAA disease have provided great insight into its pathogenesis, potentially enabling us to better clinically manage affected patients.
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