Oligomeric amyloid β preferentially targets neuronal and not glial mitochondrial‐encoded mRNAs

Mastroeni, Diego; Nolz, Jennifer; Khdour, Omar M.; Sekar, Shobana; Delvaux, Elaine; Cuyugan, Lori; Liang, Winnie S.; Hecht, Sidney M.; Coleman, Paul D.

doi:10.1016/j.jalz.2017.12.005

Cited by 16 publications

(8 citation statements)

References 76 publications

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“…However, studies about CoQ effect on neuronal mitochondria are scarce, although a decreased MRC activity and low ATP production due to neuronal CoQ deficiency has been observed [115]. Very recently, a novel CoQ analogue has been demonstrated to protect neuronal mitochondria from mitochondrial dysfunction caused by accumulation of oligomeric amyloid β (OAβ) in a neuronal model of AD [117]. This is in accordance with what we have observed in our work.…”

Section: Discussionsupporting

confidence: 91%

Parkin-mediated mitophagy and autophagy flux disruption in cellular models of MERRF syndrome

Paz

Povea-Cabello

Villalón-García

et al. 2020

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

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Mitochondrial diseases are a group of rare genetic disorders characterized by complete or partial dysfunction of mitochondria, the Highlights  MERRF patient-derived skin fibroblasts and cybrids show disrupted autophagy flux and Parkin-mediated mitophagy. Parkin-mediated mitophagy acts a cell survival mechanism in MERRF cybrids cell model. Coenzyme Q 10 acts as an enhancer of autophagy/mitophagy flux, improving cell pathophysiology. MERRF iNs harbouring the m.8344A>G mutation constitute a suitable cellular model for the screening of potential treatments for MERRF syndrome or other mitochondrial diseases. Highlights (for review)Parkin-mediated mitophagy and autophagy flux disruption in cellular models of MERRF syndrome

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Section: Discussionsupporting

confidence: 91%

Parkin-mediated mitophagy and autophagy flux disruption in cellular models of MERRF syndrome

Paz

Povea-Cabello

Villalón-García

et al. 2020

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

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“…It has also been recently reported that amyloidβ specifically causes mitochondrial damage to neurones [49] and not to microglia or astrocytes [50]. Mitochondria are very mobile in axons and thus ongoing Ca 2+ influx or further phosphorylation of Tau, causing increasing mitochondrial damage, would not be limited to site of damage but would spread throughout the axon as more mitochondria were damaged over time (Fig.…”

Section: Lose the Synapse To Save The Axonmentioning

confidence: 86%

A Unifying Hypothesis for Alzheimer’s Disease: From Plaques to Neurodegeneration

Edwards

2019

Trends in Neurosciences

108

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Evidence suggests that amyloidβ is highly toxic to synapses in a phosphoTau-dependent manner. Here I present an hypothesis that links previous evidence from the first rise of amyloidβ through to Tau tangles and neurodegeneration. In the immediate vicinity of plaques, concentrated soluble amyloidβ occurs in equilibrium with deposited forms. Initially, plaques cover only a small percentage of brain volume. Microglia, by efficiently removing damaged synapses, may prevent spread of damage along the axon, restricting damage to the immediate vicinity of plaques. However, as plaque load increases, as seen in Alzheimer's disease, an individual axon may suffer multiple points of damage, leading to dissociation of Tau, formation of a tangle and loss of the axon. As more axons suffer this fate, the network eventually degenerates. According to this hypothesis, the degree of plaque load that an individual can tolerate would depend on the efficiency of his/her microglia in removing amyloidβ-damaged synapses and the distribution of plaques, relative to axon trajectories, would determine the eventual cognitive symptoms.3 influencing disease progression and 4. the substantial variability in plaque load that individuals can carry before neurodegeneration and cognitive deficits occur.

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“…SH‐SY5Y cells (purchased from the Shanghai Institutes for Biological Sciences, China) were supplied with complete in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum, 2 m m glutamine. [ 55 ] To establish the in vitro model of tauopathy which was hyperphosphorylation of tau, SH‐SY5Y cells were induced by incubation with okadaic acid (OA, Sigma) at a final concentration of 20 n m for 24 h as a previous work, [ 19 ] and neurons were induced by incubation with OA at a final concentration of 10 n m for 4 h, according to the different sensitivity to OA. For cell treatment, OA‐damaged SH‐SY5Y cells or neurons were replaced with CM or HGF, while Con and OA‐damaged groups were replaced with α ‐MEM.…”

Section: Methodsmentioning

confidence: 99%

HGF Mediates Clinical‐Grade Human Umbilical Cord‐Derived Mesenchymal Stem Cells Improved Functional Recovery in a Senescence‐Accelerated Mouse Model of Alzheimer's Disease

Jia

Cao²,

Zhai³

et al. 2020

Advanced Science

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Stem cells have emerged as a potential therapy for a range of neural insults, but their application in Alzheimer's disease (AD) is still limited and the mechanisms underlying the cognitive benefits of stem cells remain to be elucidated. Here, the effects of clinical‐grade human umbilical cord‐derived mesenchymal stem cells (hUC‐MSCs) on the recovery of cognitive ability in SAMP8 mice, a senescence‐accelerated mouse model of AD is explored. A functional assay identifies that the core functional factor hepatocyte growth factor (HGF) secreted from hUC‐MSCs plays critical roles in hUC‐MSC‐modulated recovery of damaged neural cells by down‐regulating hyperphosphorylated tau, reversing spine loss, and promoting synaptic plasticity in an AD cell model. Mechanistically, structural and functional recovery, as well as cognitive enhancements elicited by exposure to hUC‐MSCs, are at least partially mediated by HGF in the AD hippocampus through the activation of the cMet‐AKT‐GSK3β signaling pathway. Taken together, these data strongly implicate HGF in mediating hUC‐MSC‐induced improvements in functional recovery in AD models.

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Oligomeric amyloid β preferentially targets neuronal and not glial mitochondrial‐encoded mRNAs

Abstract: Similarity of expression changes in neurons from Alzheimer's disease brain and neuronal cells treated with OAβ, and the effect of a CoQ analogue on the latter, suggests a pretreatment option to prevent OAβ toxicity, long before the damage is apparent.

Cited by 16 publications

References 76 publications

Parkin-mediated mitophagy and autophagy flux disruption in cellular models of MERRF syndrome

Parkin-mediated mitophagy and autophagy flux disruption in cellular models of MERRF syndrome

A Unifying Hypothesis for Alzheimer’s Disease: From Plaques to Neurodegeneration

HGF Mediates Clinical‐Grade Human Umbilical Cord‐Derived Mesenchymal Stem Cells Improved Functional Recovery in a Senescence‐Accelerated Mouse Model of Alzheimer's Disease

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