Reticulons as Markers of Neurological Diseases: Focus on Amyotrophic Lateral Sclerosis

Fergani, Anissa; Dupuis, Luc; Jokić, Nataša Ivančić; Larmet, Yves; Tapia, Marc de; Frydman, René; Loeffler, Jean‐Philippe; Aguilar, José-Luis González de

doi:10.1159/000089624

Cited by 15 publications

(12 citation statements)

References 142 publications

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“…In keeping with this hypothesis, altered expression levels of reticulons have been observed in several neurological disorders (Fig. 2) [23,24]. For instance, RTN3 expression is increased in cerebral tissue obtained from Alzheimer disease patients [25].…”

Section: Reticulons In Membrane Traffickingsupporting

confidence: 56%

The reticulons: Guardians of the structure and function of the endoplasmic reticulum

Sano

Bernardoni

Piacentini

2012

Experimental Cell Research

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The endoplasmic reticulum (ER) consists of the nuclear envelope and a peripheral network of tubules and membrane sheets. The tubules are shaped by a specific class of curvature stabilizing proteins, the reticulons and DP1; however it is still unclear how the sheets are assembled. The ER is the cellular compartment responsible for secretory and membrane protein synthesis. The reducing conditions of ER lead to the intra/inter-chain formation of new disulphide bonds into polypeptides during protein folding assessed by enzymatic or spontaneous reactions. Moreover, ER represents the main intracellular calcium storage site and it plays an important role in calcium signaling that impacts many cellular processes. Accordingly, the maintenance of ER function represents an essential condition for the cell, and ER morphology constitutes an important prerogative of it. Furthermore, it is well known that ER undergoes prominent shape transitions during events such as cell division and differentiation. Thus, maintaining the correct ER structure is an essential feature for cellular physiology. Now, it is known that proper ER-associated proteins play a fundamental role in ER tubules formation. Among these ER-shaping proteins are the reticulons (RTN), which are acquiring a relevant position. In fact, beyond the structural role of reticulons, in very recent years new and deeper functional implications of these proteins are emerging in relation to their involvement in several cellular processes.

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Section: Reticulons In Membrane Traffickingsupporting

confidence: 56%

The reticulons: Guardians of the structure and function of the endoplasmic reticulum

Sano

Bernardoni

Piacentini

2012

Experimental Cell Research

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“…While their biological functions remain poorly understood, diverse biochemical and functional studies suggest various potential roles of these proteins, including the shaping of the tubular ER, regulated trafficking of vesicle proteins, neurite growth and exocytosis (GrandPre et al, 2000;Kiseleva et al, 2007;Steiner et al, 2004;Chen et al, 2000;Voeltz et al, 2006;Hu et al, 2007). Altered expression levels of RTNs are found in a variety of disease states, including neurological disorders (Yan et al, 2006;Fergani et al, 2005;Bandtlow et al, 2004). We and others have demonstrated that RTNs interact with BACE1 and negatively modulate BACE1 protease activity (He et al, 2004;He et al, 2006;Murayama et al, 2006;Wojcik et al, 2007;Kume et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Reduced Amyloid Deposition in Mice Overexpressing RTN3 Is Adversely Affected by Preformed Dystrophic Neurites

Shi¹,

Prior²,

He³

et al. 2009

J. Neurosci.

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Reticulon 3 (RTN3) was initially identified as a negative modulator of BACE1, an enzyme that cleaves amyloid precursor protein (APP) to release ␤-amyloid peptide. Interestingly, RTN3 can also form aggregates after accumulation, and increased RTN3 aggregation correlates with the formation of RTN3 immunoreactive dystrophic neurites (RIDNs) in brains of Alzheimer's cases. Transgenic mice expressing RTN3 alone develop RIDNs in their hippocampus but not in their cortex. To determine the in vivo effects of RTN3 and preformed RIDNs on amyloid deposition, we crossed bitransgenic mice expressing APP and presenilin 1 (PS1) mutations with mice overexpressing RTN3. We found that amyloid deposition in cortex, the hippocampal CA3 region, and dentate gyrus was significantly reduced in triple transgenic mice compared with bitransgenic controls. However, reduction of amyloid deposition in the hippocampal CA1 region, where RIDNs predominantly formed before amyloid deposition, was less significant. Hence, preformed RTN3 aggregates in RIDNs clearly offset the negative modulation of BACE1 activity by RTN3. Furthermore, our study indicates that the increased expression of RTN3 could result in an alteration of BACE1 intracellular trafficking by retaining more BACE1 in the endoplasmic reticulum compartment where cleavage of APP by BACE1 is less favored. Our results suggest that inhibition of RTN3 aggregation is likely to be beneficial by reducing both amyloid deposition and the formation RIDNs.

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“…More than 18 murine ALS models have contributed not only to a better understanding of the disease but also to the search of potential therapeutic strategies. Nogo, also known as Neurite outgrowth inhibitor or Reticulon-4, was one of the first potential biomarkers suggested in early asymptomatic transgenic SOD1 G86R mice [36, 37]. Nogo is a member of the myelin-associated proteins, which possess axonal growth inhibitory activity.…”

Section: Potential Als Biomarkers Corresponding To Disease Progresmentioning

confidence: 99%

Amyotrophic Lateral Sclerosis: A Focus on Disease Progression

Calvo

Manzano

Mendonça

et al. 2014

BioMed Research International

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Since amyotrophic lateral sclerosis (ALS) was discovered and described in 1869 as a neurodegenerative disease in which motor neuron death is induced, a wide range of biomarkers have been selected to identify therapeutic targets. ALS shares altered molecular pathways with other neurodegenerative diseases, such as Alzheimer's, Huntington's, and Parkinson's diseases. However, the molecular targets that directly influence its aggressive nature remain unknown. What is the first link in the neurodegenerative chain of ALS that makes this disease so peculiar? In this review, we will discuss the progression of the disease from the viewpoint of the potential biomarkers described to date in human and animal model samples. Finally, we will consider potential therapeutic strategies for ALS treatment and future, innovative perspectives.

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Reticulons as Markers of Neurological Diseases: Focus on Amyotrophic Lateral Sclerosis

Cited by 15 publications

References 142 publications

The reticulons: Guardians of the structure and function of the endoplasmic reticulum

The reticulons: Guardians of the structure and function of the endoplasmic reticulum

Reduced Amyloid Deposition in Mice Overexpressing RTN3 Is Adversely Affected by Preformed Dystrophic Neurites

Amyotrophic Lateral Sclerosis: A Focus on Disease Progression

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