RNAi Therapeutic Potentials and Prospects in CNS Disease

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

Cerebrovascular Atherosclerosis: Cognitive Dysfunction Progress and Autophagic Regression

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

Microscopic study of orbital textures

Many interesting spin and orbital transport phenomena originate from orbital textures, referring to $\vec{k}$-dependent orbital states. Most of previous works are based on symmetry analysis to model the orbital texture and analyze its consequences. However the microscopic origins of orbital texture and its strength are largely unexplored. In this work, we derive the orbital texture Hamiltonians from microscopic tight-binding models for various situations. To form an orbital texture, $\vec{k}$-dependent hybridization of orbital states are necessary. We reveal two microscopic mechanisms for the hybridization: (i) lattice structure effect and (ii) mediation by other orbital states. By considering the orbital hybridization, we not only reproduce the orbital Hamiltonian obtained by the symmetry analysis but also reveal previously unreported orbital textures like orbital Dresselhaus texture and anisotropic orbital texture. The orbital Hamiltonians obtained here would be useful for analyzing the orbital physics and designing the materials suitable for spin-orbitronic applications. We show that our theory also provides useful microscopic insight into physical phenomena such as the orbital Rashba effect and the orbital Hall effect. Our formalism is so generalizable that one can apply it to obtain effective orbital Hamiltonians for arbitrary orbitals in the presence of periodic lattice structures.Comment: 15 pages, 12 figure