Dysregulation of microRNA-219 promotes neurodegeneration through post-transcriptional regulation of tau

Santa-María, Ismael; Alaniz, Maria Eugenia; Renwick, Neil; Cela, Carolina; Fulga, Tudor A.; Vactor, David Van; Tuschl, Thomas; Clark, Lorraine N.; Shelanski, Michael L.; McCabe, Brian D.; Crary, John F.

doi:10.1172/jci78421

Cited by 178 publications

(122 citation statements)

References 20 publications

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“…Tau in oligodendrocytes is important during neuronglia contact formation which may link Tau dysfunction to developmental disorders [72]. Since Tau protein levels are crucial for toxicity, the identification of micro-RNAs regulating Tau expression will open up new possibilities to interfere with Tau protein levels [73,74 ].…”

Section: Resultsmentioning

confidence: 99%

Tau neurotoxicity and rescue in animal models of human Tauopathies

Krüger

Mandelkow

2016

Current Opinion in Neurobiology

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Section: Resultsmentioning

confidence: 99%

Tau neurotoxicity and rescue in animal models of human Tauopathies

Krüger

Mandelkow

2016

Current Opinion in Neurobiology

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“…Antisense targeting of tau to decrease expression diminishes seizures in mice, indicating that tau may mediate a pathological signaling network in neurons (57). Recently, miR-219 was shown to bind the 3 untranslated region of tau RNA and downregulate its expression (58). In AD, miR-219 is downregulated, possibly indicating a direct role in pathogenesis of the disease and an opportunity for therapeutic intervention.…”

Section: Neurofibrillary Tangles As Drug Targetsmentioning

confidence: 99%

Update on Alzheimer's Disease Therapy and Prevention Strategies

2017

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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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“…The described processes of heme biosynthesis are tightly orchestrated and must be coordinated with iron acquisition and globin gene expression during erythroid differentiation. 78,79 …”

Section: Porphyrin and Heme Biosynthesismentioning

confidence: 99%

Intracellular iron and heme trafficking and metabolism in developing erythroblasts

Kafina

Paw

2017

Metallomics

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Vertebrate red blood cells (RBCs) arise from erythroblasts in the human bone marrow through a process known as erythropoiesis. Iron uptake is a crucial hallmark, essential for heme biosynthesis in the differentiating erythroblasts, which are dedicated to producing hemoglobin. Erythropoiesis is facilitated by a network of intracellular transport proteins, chaperones, and circulating hormones. Intracellular iron is targeted to the mitochondria for incorporation into a porphyrin ring to form heme and cytosolic iron-sulfur proteins, including Iron Regulatory Protein 1 (IRP1). These processes are tightly regulated to prevent both excess and insufficient levels of iron and heme precursors. Crosstalk between the heme and iron-sulfur synthesizing pathways has been demonstrated to serve as a regulatory feedback mechanism. The activity of δ-aminolevulinic acid synthase (ALAS), the first and rate-limiting enzyme of heme biosynthesis, is a fundamental node of this regulation. Recently, the mitochondrial unfoldase, ClpX, has received attention as a novel key player that modulates this step in heme biogenesis, implicating a role in the pathophysiology of anemic diseases. This chapter reviews the canonical pathways in intracellular iron and heme trafficking and recent findings of iron and heme metabolism in vertebrate red cells. A discussion of the molecular approaches to studying iron and heme transport is provided to highlight opportunities for revealing therapeutic targets.

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Dysregulation of microRNA-219 promotes neurodegeneration through post-transcriptional regulation of tau

Cited by 178 publications

References 20 publications

Tau neurotoxicity and rescue in animal models of human Tauopathies

Tau neurotoxicity and rescue in animal models of human Tauopathies

Update on Alzheimer's Disease Therapy and Prevention Strategies

Intracellular iron and heme trafficking and metabolism in developing erythroblasts

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