Interplay between TDP-43 and docosahexaenoic acid-related processes in amyotrophic lateral sclerosis

Cacabelos, Daniel; Ayala, Victòria; Granado-Serrano, Ana Belén; Jové, Mariona; Torres, Pascual; Boada, Jordi; Cabré, Rosanna; Ramírez‐Núñez, Omar; Gonzalo, Hugo; Soler-Cantero, Aranzazu; Serrano, José C. E.; Bellmunt, Marı́a Josep; Bolaño-Romero, María Paz; Motilva, María‐José; Nonaka, Takashi; Hasegawa, Masato; Ferrer, Isidre; Pamplona, Reinald; Portero‐Otín, Manuel

doi:10.1016/j.nbd.2016.01.007

Cited by 31 publications

(19 citation statements)

References 46 publications

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“…Additionally, drebrin is decreased in other neurodegenerative diseases such as amyotrophic lateral sclerosis (Cacabelos et al . ). Moreover, progranulin that is involved in the pathogenesis of frontotemporal dementia is known to interact with drebrin (Xu et al .…”

Section: Drebrin Disappearance As a Pathogenic Characteristic Of Alzhmentioning

confidence: 97%

“…Drebrin decrease is now a hallmark of the AD brain Ma et al 2015), as well as amyloid plaques (senile plaques) and neurofibrillary tangles (Selkoe and Hardy 2016). Additionally, drebrin is decreased in other neurodegenerative diseases such as amyotrophic lateral sclerosis (Cacabelos et al 2016). Moreover, progranulin that is involved in the pathogenesis of frontotemporal dementia is known to interact with drebrin (Xu et al 2015).…”

Section: Drebrin Disappearance As a Pathogenic Characteristic Of Alzhmentioning

confidence: 99%

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The role of drebrin in neurons

Shirao

Hanamura

Koganezawa

et al. 2017

Journal of Neurochemistry

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Drebrin is an actin-binding protein that changes the helical pitch of actin filaments (F-actin), and drebrin-decorated F-actin shows slow treadmilling and decreased rate of depolymerization. Moreover, the characteristic morphology of drebrindecorated F-actin enables it to respond differently to the same signals from other actin cytoskeletons. Drebrin consists of two major isoforms, drebrin E and drebrin A. In the developing brain, drebrin E appears in migrating neurons and accumulates in the growth cones of axons and dendrites. Drebrin E-decorated Factin links lamellipodium F-actin to microtubules in the growth cones. Then drebrin A appears at nascent synapses and drebrin A-decorated F-actin facilitates postsynaptic molecular assembly. In the adult brain, drebrin A-decorated F-actin is concentrated in the central region of dendritic spines. During long-term potentiation initiation, NMDA receptor-mediated Ca 2+ influx induces the transient exodus of drebrin A-decorated F-actin via myosin II ATPase activation. Because of the unique physical characteristics of drebrin A-decorated F-actin, this exodus likely contributes to the facilitation of F-actin polymerization and spine enlargement. Additionally, drebrin reaccumulation in dendritic spines is observed after the exodus. In our drebrin exodus model of structure-based synaptic plasticity, reestablishment of drebrin A-decorated F-actin is necessary to keep the enlarged spine size during long-term potentiation maintenance. In this review, we introduce the genetic and biochemical properties of drebrin and the roles of drebrin in early stage of brain development, synaptic formation and synaptic plasticity. Further, we discuss the pathological relevance of drebrin loss in Alzheimer's disease.

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Section: Drebrin Disappearance As a Pathogenic Characteristic Of Alzhmentioning

confidence: 97%

Section: Drebrin Disappearance As a Pathogenic Characteristic Of Alzhmentioning

confidence: 99%

The role of drebrin in neurons

Shirao

Hanamura

Koganezawa

et al. 2017

Journal of Neurochemistry

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“…In a large-scale genetic screen using the Drosophila model, a major class of modifiers of the VAP mutant phenotype comprised proteins involved in lipid droplet function (Sanhueza et al, 2015). Changes in lipid composition of neurons from ALS patients have been reported, and it has been shown that lipids affect the function of one of the major causative agents of ALS, TDP-53 (Cacabelos et al, 2016;Cutler et al, 2002). TDP-53 has also been shown to disrupt ER-mitochondria MCS mediated by VAP (Stoica et al, 2014).…”

Section: Disruption Of Lipid Trafficking In Human Diseasementioning

confidence: 99%

Lipids and Their Trafficking: An Integral Part of Cellular Organization

2016

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An evolutionarily conserved feature of cellular organelles is the distinct phospholipid composition of their bounding membranes, which is essential to their identity and function. Within eukaryotic cells, two major lipid territories can be discerned, one centered on the endoplasmic reticulum and characterized by membranes with lipid packing defects, the other comprising plasma-membrane-derived organelles and characterized by membrane charge. We discuss how this cellular lipid organization is maintained, how lipid flux is regulated, and how perturbations in cellular lipid homeostasis can lead to disease.

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“…For this reason, they have been involved in the redox homeostasis of membranes [34], and its Previous data have characterized plasmalogens in the nuclear envelope of postmytotic tissues such as myocardium [35]. Peroxisomes contribute to plasmalogen synthesis, and previous data of our group describe alterations in peroxisomal enzymes in ALS tissues [36]. Whether the loss of plasmalogen present in ALS nuclei is potentially derived from this peroxisomal disturbance and whether it contributes to ALS pathophysiology is still unknown.…”

Section: Discussionmentioning

confidence: 98%

Nuclear lipidome is altered in amyotrophic lateral sclerosis: a preliminary study

Ramírez‐Núñez¹,

Jové²,

Torres³

et al. 2019

Preprint

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In this pilot study, we show that nuclei in spinal cord from ALS patients exhibit a differential lipidomic signature. Among the differential lipid species we could annotate 41 potential identities. These comprise membrane-bound lipids such as phosphatidylethanolamines -including plasmalogens-and phosphatidylcholines but also other lipid classes such as glycosphingolipids, diacylglycerols, and triacylglycerides (potentially present as nuclear lipid droplets). These results were orthogonally validated by showing loss of alkyldihydroxyacetonephosphate synthase (AGPS), a key peroxisomal enzyme in plasmalogen synthesis, both in ALS necropsy samples, in human motor neurons derived from iPSC from ALS patients and in hSOD-G93A transgenic mice. Further, diacylglycerol content changes were associated to ALS-linked variations in relatedenzymes, such as phospholipase C ßI (PLCßI), the source of nuclear diacylglycerol, and protein kinase CßII (PKCßII), whose function partially depends on nuclei concentration of diacylglycerol. These results point out for not only a role of nuclear membrane lipids but also to lipids present in the nucleoplasm, suggesting an undisclosed role for this part of the subcellular lipidome in ALS pathophysiology.

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Interplay between TDP-43 and docosahexaenoic acid-related processes in amyotrophic lateral sclerosis

Cited by 31 publications

References 46 publications

The role of drebrin in neurons

The role of drebrin in neurons

Lipids and Their Trafficking: An Integral Part of Cellular Organization

Nuclear lipidome is altered in amyotrophic lateral sclerosis: a preliminary study

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