RNA and protein-dependent mechanisms in tauopathies: consequences for therapeutic strategies

Gallo, Jean‐Marc; Noble, Wendy; Martin, T. Rodriguez

doi:10.1007/s00018-007-6513-4

Cited by 31 publications

(22 citation statements)

References 141 publications

(176 reference statements)

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“…A mutation that falls into a silencer or enhancer regions either promotes or decreases exon usage, respectively (reviewed in [80]). Mutations in exon 10 alter its normal fraction of inclusion and changes of pre-mRNA encoding 3R and 4R repeat tau isoforms were found associated with FTDP-17 (recently reviewed by [81], [82]). These data clearly suggested that the splicing mutations cause the neuropathology by changing the ratio between the 3R and 4R isoforms.…”

Section: Examples Of Diseases Caused By Alternative Splicingmentioning

confidence: 99%

Alternative splicing and disease

Tazi

Bakkour

Stamm

2009

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

484

365

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Almost all protein-coding genes are spliced and their majority is alternatively spliced. Alternative splicing is a key element in eukaryotic gene expression that increases the coding capacity of the human genome and an increasing number of examples illustrates that the selection of wrong splice sites causes human disease. A fine-tuned balance of factors regulates splice site selection. Here, we discuss well-studied examples that show how a disturbance of this balance can cause human disease. The rapidly emerging knowledge of splicing regulation now allows the development of treatment options.

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Section: Examples Of Diseases Caused By Alternative Splicingmentioning

confidence: 99%

Alternative splicing and disease

Tazi

Bakkour

Stamm

2009

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

484

365

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“…To increase specificities, multiple technologies to target aberrant splicing (Gallo et al, 2007) have been examined for SMN genes. One strategy that is employed to stimulate inclusion or exclusion of exon 7 is to use bifunctional oligoribonucleotides, which are molecules made of an anti-sense sequence that bind to an exonic element and a sequence tethering a trans factor, or link to a peptide domain mimicking a trans splicing factor (Cartegni and Krainer, 2003;Skordis et al, 2003;Villemaire et al, 2003).…”

Section: Sma Animal Modelsmentioning

confidence: 99%

Targeting RNA-Splicing for SMA Treatment

Zhou

Zheng

Shen

2012

Molecules and Cells

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The central dogma of DNA-RNA-protein was established more than 40 years ago. However, important biological processes have been identified since the central dogma was developed. For example, methylation is important in the regulation of transcription. In contrast, proteins, are more complex due to modifications such as phosphorylation, glycosylation, ubiquitination, or cleavage. RNA is the mediator between DNA and protein, but it can also be modulated at several levels. Among the most profound discoveries of RNA regulation is RNA splicing. It has been estimated that 80% of pre-mRNA undergo alternative splicing, which exponentially increases biological information flow in cellular processes. However, an increased number of regulated steps inevitably accompanies an increased number of errors. Abnormal splicing is often found in cells, resulting in protein dysfunction that causes disease. Splicing of the survival motor neuron (SMN) gene has been extensively studied during the last two decades. Accumulating knowledge on SMN splicing has led to speculation and search for spinal muscular atrophy (SMA) treatment by stimulating the inclusion of exon 7 into SMN mRNA. This mini-review summaries the latest progress on SMN splicing research as a potential treatment for SMA disease.

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“…The abnormal hyperphosphorylation and altered conformation of the microtubule-associated protein (MAP) tau precedes its assembly into paired helical filaments and its accumulation in NFTs (Buee et al, 2000; Andorfer et al, 2003; Gallo et al, 2007; Hanger et al, 2009; Iqbal et al, 2009). Tau is a substrate for several protein kinases, such as glycogen synthase kinase-3 (GSK-3) and cyclin-dependent kinase (cdk5), and for phosphatases such as protein phosphatase-2A (PP2A); PP2A activity is down-regulated in the AD brain (Buee et al, 2000; Andorfer et al, 2003; Gallo et al, 2007; Hernandez and Avila, 2008; Hanger et al, 2009; Iqbal et al, 2009; Hernández et al, 2010).…”

Section: Is There a Link Between At2r Activation And Ad?mentioning

confidence: 99%

Angiotensin II, a neuropeptide at the frontier between endocrinology and neuroscience: is there a link between the angiotensin II type 2 receptor and Alzheimer’s disease?

et al. 2011

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Amyloid-β peptide deposition, abnormal hyperphosphorylation of tau, as well as inflammation and vascular damage, are associated with the development of Alzheimer’s disease (AD). Angiotensin II (Ang II) is a peripheral hormone, as well as a neuropeptide, which binds two major receptors, namely the Ang II type 1 receptor (AT1R) and the type 2 receptor (AT2R). Activation of the AT2R counteracts most of the AT1R-mediated actions, promoting vasodilation, decreasing the expression of pro-inflammatory cytokines, both in the brain and in the cardiovascular system. There is evidence that treatment with AT1R blockers (ARBs) attenuates learning and memory deficits. Studies suggest that the therapeutic effects of ARBs may reflect this unopposed activation of the AT2R in addition to the inhibition of the AT1R. Within the context of AD, modulation of AT2R signaling could improve cognitive performance not only through its action on blood flow/brain microcirculation but also through more specific effects on neurons. This review summarizes the current state of knowledge and potential therapeutic relevance of central actions of this enigmatic receptor. In particular, we highlight the possibility that selective AT2R activation by non-peptide and highly selective agonists, acting on neuronal plasticity, could represent new pharmacological tools that may help improve impaired cognitive performance in AD and other neurological cognitive disorders.

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RNA and protein-dependent mechanisms in tauopathies: consequences for therapeutic strategies

Cited by 31 publications

References 141 publications

Alternative splicing and disease

Alternative splicing and disease

Targeting RNA-Splicing for SMA Treatment

Angiotensin II, a neuropeptide at the frontier between endocrinology and neuroscience: is there a link between the angiotensin II type 2 receptor and Alzheimer’s disease?

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