Short interfering RNA (siRNA): tool or therapeutic?

Cejka, Daniel; Losert, Doris; Wacheck, Volker

doi:10.1042/cs20050162

Cited by 86 publications

(68 citation statements)

References 101 publications

(116 reference statements)

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“…There have been few reports on the use of siRNA in animal models (193) and the development of appropriate vector systems is a prerequisite (194) before siRNA can be regarded as a suitable experimental tool for in vivo studies (195). Use of siRNA in cell culture has been achieved with striking potency at a relatively low concentration (190,196,199).…”

Section: Future Trends: Inflammation Lipidomics and Rna Silencingmentioning

confidence: 99%

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Integration of cytokine biology and lipid metabolism in stroke

Adibhatla

Dempsy²,

Hatcher³

2008

Front Biosci

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Cytokines regulate the innate and adaptive immune responses and are pleiotropic, redundant and multifunctional. Expression of most cytokines, including TNF-α and IL-1α/ß, is very low in normal brain. Metabolism of lipids is of particular interest due to their high concentration in the brain. Inflammatory response after stroke suggests that cytokines (TNF-α, IL-1 α/ß, IL-6), affect the phospholipid metabolism and subsequent production of eicosanoids, ceramide, and ROS that may potentiate brain injury. Phosphatidylcholine and sphingomyelin are source for lipid messengers. Sphingomyelin synthase serves as a bridge between metabolism of glycerolipids and sphingolipids. TNF-α and IL-1 α/ß can induce phospholipases (A 2 , C, and D) and sphingomyelinases, and concomitantly proteolyse phosphatidylcholine and sphingomyelin synthesizing enzymes. Together, these alterations contribute to loss of phosphatidylcholine and sphingomyelin after stroke that can be attenuated by inhibiting TNF-α or IL-1 α/ß signaling. Inflammatory responses are instrumental in the formation and destabilization of atherosclerotic plaques. Secretory PLA 2 IIA is found in human atherosclerotic lesions and is implicated in initiation, progression and maturation of atherosclerosis, a risk factor for stroke. Lipoprotein-PLA 2 , part of apolipoprotein B-100 of LDL, plays a role in vascular inflammation and coronary endothelial dysfunction. Cytokine antagonism attenuated secretory PLA 2 IIA actions, suggesting cytokine-lipid integration studies will lead to new concepts contributing to bench-to-bedside transition for stroke therapy.

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Section: Future Trends: Inflammation Lipidomics and Rna Silencingmentioning

confidence: 99%

“…RNA interference (RNAi) (190)(191)(192) takes advantage of a naturally occurring process to degrade RNA, the intermediary translator between the DNA of genes and the protein molecules they encode. RNAi takes advantage of a naturally occurring process to degrade RNA.…”

Section: Future Trends: Inflammation Lipidomics and Rna Silencingmentioning

confidence: 99%

Integration of cytokine biology and lipid metabolism in stroke

Adibhatla

Dempsy²,

Hatcher³

2008

Front Biosci

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“…RNA interference (RNAi) [98][99][100] takes advantage of a naturally occurring process to degrade RNA. RNAi selectively and temporarily switches off specific genes, providing a powerful tool to analyze protein function and biochemical pathways.…”

Section: Future Trends: Lipidomics and Rna Silencingmentioning

confidence: 99%

Role Of Lipids In Brain Injury And Diseases

2007

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SummaryLipid metabolism is of particular interest due to its high concentration in CNS. The importance of lipids in cell signaling and tissue physiology is demonstrated by many CNS disorders and injuries that involve deregulated metabolism. The long suffering lipid field is gaining reputation and respect as evidenced through the Center of Biomedical Research Excellence in Lipidomics and Pathobiology (COBRE), Lipid MAPS (Metabolites And Pathways Strategy) Consortium sponsored by NIH, European initiatives for decoding the lipids through genomic approaches, and Genomics of Lipidassociated Disorder (GOLD) project initiated by Austrian government. This review attempts to provide an overview of the lipid imbalances associated with neurological disorders (Alzheimer's, Parkinson's; Niemann-Pick; Multiple sclerosis, Huntington, amyotrophic lateral sclerosis, schizophrenia, bipolar disorders and epilepsy) and CNS injury (Stroke, traumatic brain injury; and spinal cord injury) and a few provocative thoughts. Lipidomic analyses along with RNA silencing will provide new insights into the role of lipid intermediates in cell signaling and hopefully open new avenues for prevention or treatment options. KeywordsAlzheimer's disease; Arachidonic acid; CDP-choline; CNS injury; Docosahexaenoic acid; Huntington disease; Lipid peroxidation; Neurodegenerative diseases; Phospholipases; Phospholipids; Stroke Lipids and the Central Nervous System (CNS)Phospholipids are important components of all mammalian cells and have a variety of biological functions: 1) formation of lipid bilayers that provide structural integrity necessary for protein function 2) function as an energy reservoir (for example triglycerides) and 3) serve as precursors for various second messengers such as arachidonic acid (ArAc), docosahexaenoic acid (DHA), ceramide, 1,2-diacylglycerol (DAG), phosphatidic acid, and lyso-phosphatidic acid. Lipids comprise a large number of chemically distinct molecules arising from combinations of fatty acids with various backbone structures. Overall, mammalian cells may contain ~1000-2000 lipid species [1]. Lipids are classified into eight categories (fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids, and polyketides) [2]. Subtypes of these eight lipid classes are given in Table 1 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript metabolism may be of particular importance for the CNS, as this organ has a high concentration of lipids, second only to adipose tissue.Neurodegenerative diseases, mental disorders, stroke and CNS traumas are problems of vast clinical importance. Currently there exists no cure for these CNS injuries and disorders, resulting in a huge impact on quality of life and an economic burden on society (Table 2, based on the US population statistics). The crucial role of lipids in tissue physiology and cell signaling is demonstrated by the many neurological disorders, including bipolar disorders and schizophrenia, and neurodegenerative ...

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“…Although advances are being made (1)(2)(3), currently, only a few approaches potentially feasible in patients have been described (4)(5)(6)(7)(8). Our laboratory has developed an anti-transferrin receptor (TfR) single-chain antibody fragment-directed nanoimmunoliposome (scL), which self-assembles into f100-nm size particles.…”

Section: Introductionmentioning

confidence: 99%