Kyoungjoo Cho

By Kyoung Joo Cho and Gyung Whan Kim

Over the past 20 years, RNA interference (RNAi) technology has provided a new regulatory paradigm in biology. This technique can efficiently suppress target genes of interest in mammalian cells. Small non-coding RNAs play important roles in gene regulation, including both in post-transcriptional and in translational regulation. For in vivo experiments, continuous development has resulted in successful new ways of designing, identifying, and delivering small interfering RNAs (siRNAs). Proof-of-principle studies in vivo have clearly demonstrated that both viral and non-viral delivery methods can provide selective and potent target gene suppression without any clear toxic effects. There are also the persistent problems with off-target effects (OTEs), competition with cellular RNAi components, and effective delivery in vivo. Although recent researches and trials from a large number of animal model studies have confirmed that most OTEs are not dangerous, other important issues need to be addressed before RNAi-based drugs are ready for clinical use. Currently, RNAi may be harnessed as a new therapeutic modality for brain diseases. Finally, there are already several RNAi-based human clinical trials in progress. It is hoped that this technology will have also effective applications in human central nervous system (CNS)-related disease.

Part of the book: RNA Interference

By Kyoung Joo Cho and Gyung Whan Kim

As the aging of society, metabolic disorders have become a major concern and a major cause for cardio- and neurovascular diseases such as atherosclerosis, stroke, and even cognitive decline. This chapter shows the progressive plaque formation mechanisms and regression under autophagic flow in both experimental and clinical side. Atherosclerotic plaque formation is not irrevocable. Clinical and experimental reports accept that atherosclerosis can regress after statin treatment. This chapter focuses on autophagic roles in atherosclerotic plaque formation, progression, and regression. Another focus is on the relationship between atherosclerosis and an increased risk of cognitive decline and further conversion from mild cognitive impairment (MCI) to dementia. There has been broad and strong support on the relationship between atherosclerotic severity and cognitive function. Ultrasound findings such as intima-media thickness (IMT) and plaque numbers could potentially be useful in identifying individuals with a higher risk of progression from cognitive decline according to morphological criteria. This also suggests the possibility as a predictive indicator of MCI and dementia by considering the presence of atherosclerotic changes. Focusing on therapeutics, this chapter provides mechanisms for regressing atherosclerotic plaques. Autophagy suggests therapeutic possibilities for atherosclerosis and it consequently paves the way for preventing cognitive impairment.

Part of the book: Atherosclerosis

By Kyoungjoo Cho

Brain function is supported by the cerebrovascular system, and changes in vascular phenotype and function through aging process make the brain more susceptible to neurodegenerative diseases, particularly cognitive decline. Correspondingly, the incidence of dementia and the prevalence of neurodegenerative diseases have also increased. In aging, the vessels have been exposed to the inflammatory state by harmful factors referred to as the senescence-associated secretory phenotype (SASP). Aging is a complex process that is associated with accumulated cellular stresses and an increased stress response. The aging in the brain includes structural and functional changes, which cause brain pathologies in the elderly. Particularly, damaged neurovascular event can be a consequent trigger in the pathology of vascular cognitive impairment. This chapter introduces the current knowledge on cognitive decline according to cerebrovascular aging relevant to endothelial senescence and the changes in the SASPs.

Part of the book: New Insight into Cerebrovascular Diseases