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Disease Models and Mechanisms 03/2013; 6(2):424-433 (DMM009761) suppl fig 1

March 2013

March 2013

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Istituto Italiano di Tecnologia

Università degli Studi di Genova

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Fig. S1. A schematic view of the SORL1 locus. Protein sequences were analyzed in silico showing alternative protein variants (see Aceview annotations at www.ncbi.nlm.nih.gov/IEB/Research/Acembly).

Figures - uploaded by Tullio Florio

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Content uploaded by Tullio Florio

Content may be subject to copyright.

Fig. S1. A schematic view of the SORL1 locus. Protein sequences were analyzed in silico showing alternative pro-

tein variants (see Aceview annotations at www.ncbi.nlm.nih.gov/IEB/Research/Acembly).

Gene SORL1 5’ 3’ encoded on plus strand of chromosome 11 from 120828122 to 121009681

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Schematic view of SORL1 protein variants

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ResearchGate has not been able to resolve any references for this publication.

An intronic ncRNA-dependent regulation of SORL1 expression affecting A formation is upregulated in post-mortem Alzheimer's disease brain samples

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March 2013

Eleonora Ciarlo · Sara Massone · Ilaria Penna · Mario Nizzari · Aldo Pagano

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Karim A Alkadhi

There has been a recent upsurge of scientific reports about the benefits of regular physical exercise for general health and particularly for mental health. Healthy diet and physical activity have emerged as promising low-cost measures for protection against a variety of diseases including Alzheimer's and other forms of dementias. Additionally, regular exercise is known to stop declining memory ... [Show full abstract] and improve recall in a variety of conditions including aging and chronic stress. This has been shown both in humans and in animal models of these disorders. For example, experiments from this laboratory clearly showed that regular exercise prevented memory impairment in an animal model of Alzheimer's disease (see Figure 1). Fig. 1. Memory test showing impaired memory recall in Alzheimer's (AD) model indicated by higher number of errors made by the model (marked by *). Note the exercised AD model exhibits normal memory. As an indicator of memory, we also induced and recorded brain electrical activity directly from brains of anesthetized animals to make sure that what we saw in memory test is reflected in brain activity in two areas of the brain known to be responsible for memory formation (see Figure 2). We also wanted to compare the effect of both Alzheimer's disease and exercise on the two areas of the brain. One area is called "Cornu Amonis" and the other "dentate gyrus". The latter area has the unique ability to generate new nerve cells. We compared the effect of Alzheimer's dementia and exercise on brain activity as well as on levels of enzymes and protein molecules essential for memory formation.

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September 2012

Article

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An intronic ncRNA-dependent regulation of SORL1 expression affecting A formation is upregulated in p...

March 2013 · Disease Models and Mechanisms

Recent studies indicated sortilin-related receptor 1 (SORL1) to be a risk-gene for late-onset Alzheimer's Disease (AD), although its role in the aetiology and/or progression of this disorder is not fully understood. Here, we report the finding of a novel non-coding (nc) RNA (hereafter referred to as 51A) that maps in antisense (AS) configuration in intron 1 of SORL1 gene. 51A expression drives a ... [Show full abstract] splicing shift of SORL1 from the synthesis of the canonical long protein variant 1 to an alternatively spliced protein form. This process, resulting in a decreased synthesis of SORL1 variant 1, is associated with an impaired processing of APP, leading to increase of Aβ formation. Interestingly, we found that 51A is expressed in human brains, being frequently up-regulated in cerebral cortices from Alzheimer's disease patients. Altogether these findings document a novel ncRNA-dependent regulatory pathway that might have relevant implications in neurodegeneration.

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NDM29, a RNA polymerase III-dependent non coding RNA, promotes amyloidogenic processing of APP and a...

May 2012 · Biochimica et Biophysica Acta

Neuroblastoma Differentiation Marker 29 (NDM29) is a RNA polymerase (pol) III-transcribed non-coding (nc) RNA whose synthesis drives neuroblastoma (NB) cell differentiation to a nonmalignant neuron-like phenotype. Since in this process a complex pattern of molecular changes is associated to plasma membrane protein repertoire we hypothesized that the expression of NDM29 might influence also key ... [Show full abstract] players of neurodegenerative pathways. In this work we show that the NDM29-dependent cell maturation induces amyloid precursor protein (APP) synthesis, leading to the increase of amyloid β peptide (Aβ) secretion and the concomitant increment of Aβ x-42/Aβ x-40 ratio. We also demonstrate that the expression of NDM29 RNA, and the consequent increase of Aβ formation, can be promoted by inflammatory stimuli (and repressed by anti-inflammatory drugs). Moreover, NDM29 expression was detected in normal human brains although an abnormal increased synthesis of this ncRNA is induced in patients affected by neurodegenerative diseases. Therefore, the complex of events triggered by NDM29 expression induces a condition that favors the formation of Aβ peptides in the extracellular space, as it may occur in Alzheimer's Disease (AD). In addition, these data unexpectedly show that a pol III-dependent small RNA can act as key regulator of brain physiology and/or pathology suggesting that a better knowledge of this portion of the human transcriptome might provide hints for neurodegeneration studies.

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The most frequently used technique to study the expression profile of genes involved in common neurological disorders is quantitative real-time RT-PCR, which allows the indirect detection of very low amounts of selected mRNAs in tissue samples. Expression analysis by RT-qPCR requires an appropriate normalization to the expression level of genes characterized by a stable, constitutive ... [Show full abstract] transcription. However, the identification of a gene transcribed at a very stable level is difficult if not impossible, since significant fluctuations of the level of mRNA synthesis often accompanies changes of cell behavior. The aim of this study is to identify the most stable genes in postmortem human brain samples of patients affected by Alzheimer's disease (AD) suitable as reference genes. The experiments analyzed 12 commonly used reference genes in brain samples from eight individuals with AD and seven controls. After a careful analysis of the results calculated by geNorm and NormFinder algorithms, we found that CYC1 and EIF4A2 are the best reference genes. We remark on the importance of the determination of the best reference genes for each sample to be analyzed and suggest a practical combination of reference genes to be used in the analysis of human postmortem samples.