An update on the interactions between Alzheimer's disease, autophagy and inflammation

Bostancıklıoğlu, Mehmet

doi:10.1016/j.gene.2019.04.040

Cited by 67 publications

(49 citation statements)

References 167 publications

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“…Having established the involvement of autophagy and p62 in regulation of the inflammatory immune response, we examined whether p62 accumulation mediates SiNP-triggered airway inflammation in vitro [26,27]. After treatment with SiNPs, IL-1 and IL-6 gene expression levels increased dramatically in a dose-dependent manner (Fig.…”

Section: Sinp-associated P62 Triggered Inflammation Through Nf-κb Actmentioning

confidence: 99%

p62/SQSTM1 accumulation due to degradation inhibition and transcriptional activation plays a critical role in silica nanoparticle-induced airway inflammation via NF-κB activation

Yang

Sun

et al. 2020

J Nanobiotechnol

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Background: Most nanoparticles (NPs) reportedly block autophagic flux, thereby upregulating p62/SQSTM1 through degradation inhibition. p62 also acts as a multifunctional scaffold protein with multiple domains, and is involved in various cellular processes. However, the autophagy substrate-independent role of p62 and its regulation at the transcriptional level upon NPs exposure remain unclear. Results: In this work, we exposed BEAS-2b cells and mice to silica nanoparticles (SiNPs), and found that SiNPs increased p62 protein levels in vivo and vitro. Then, we further explored the role and mechanism of SiNPs-stimulated p62 in vitro, and found that p62 degradation was inhibited due to autophagic flux blockade. Mechanistically, SiNPs blocked autophagic flux through impairment of lysosomal capacity rather than defective autophagosome fusion with lysosomes. Moreover, SiNPs stimulated translocation of NF-E2-related factor 2 (Nrf2) to the nucleus from the cytoplasm, which upregulated p62 transcriptional activation through direct binding of Nrf2 to the p62 promoter. Nrf2 siRNA dramatically reduced both the mRNA and protein levels of p62. These two mechanisms led to p62 protein accumulation, thus increasing interleukin (IL)-1 and IL-6 expression. SiNPs activated nuclear factor kappa B (NF-κB), and this effect could be alleviated by p62 knockdown. Conclusion: SiNPs caused accumulation of p62 through both pre-and post-translational mechanisms, resulting in airway inflammation. These findings improve our understanding of SiNP-induced pulmonary damage and the molecular targets available to mitigate it.

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Section: Sinp-associated P62 Triggered Inflammation Through Nf-κb Actmentioning

confidence: 99%

p62/SQSTM1 accumulation due to degradation inhibition and transcriptional activation plays a critical role in silica nanoparticle-induced airway inflammation via NF-κB activation

Yang

Sun

et al. 2020

J Nanobiotechnol

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“…Stresses such as infection, autoimmunity, or traumatic brain injury can trigger neuroinflammation that aggravates brain lesions, resulting in neuron degeneration and synaptic dysfunction [24][25][26]. We found that levels of inflammatory factors varied inversely with the severity of POCD, and that activating autophagy led to lower cytokine levels, while inhibiting autophagy increased the levels.…”

Section: Discussionmentioning

confidence: 75%

Autophagy attenuates postoperative cognitive dysfunction by up-regulating cystatin C in aged rats undergoing splenectomy

Zhou

Cai

et al. 2019

Preprint

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B ackground : This study aimed to explore whether autophagy can attenuate postoperative cognitive dysfunction (POCD) by up-regulating cystatin C (CysC) in aged rats undergoing splenectomy. Methods : Rats were randomized into four groups ( n = 10 per group): normal control (CON), surgery (SUR), surgery + rapamycin (autophagy inducer) at 1.0 mg/kg/d (RAP), and surgery + 3-methyladenine (autophagy inhibitor) at 3.0 mg/kg/d (3-MA). Treatments were carried out for four weeks.Postoperative learning and memory were assessed using the Morris water maze. Hippocampal expression of the autophagy-related proteins ATG5, LC-3B, Beclin1, and p62 as well as Cys C was assayed using Western blotting and real-time polymerase chain reaction. Results: SUR animals showed higher levels of autophagy and higher expression of autophagy proteins and Cys C than CON animals. These levels were even higher in RAP animals, which also showed lower levels of the inflammatory factors IL-1β, IL-6 and TNF-α than the other groups. Learning and memory functions were higher in RAP animals than in the other groups on days 5 and 7. Effects of 3-MA were opposite to those of RAP. Conclusion : Autophagy improves learning and memory in aged rats following splenectomy, which may involve up-regulation of Cys C and attenuation of neuro-inflammation. BackgroundAutophagy, a self-degradation progress involving the lysosome system, helps maintain cell homeostasis, e.g. following exposure to injury, and its dysregulation can contribute to many diseases [1]. During autophagy, autophagy gene-related protein complexes induce the conjugation of microtubule-associated protein 1A/1B-light chain 3 (LC3B-I) to phosphatidylethanolamine to form LC3B-II, which helps form autophagosomes [2,3]. LC3B interacts with sequestosome-1/p62 and sorts cytosolic cargo via a ubiquitin binding domain [4]. Mammalian target of rapamycin and Beclin1 are also key molecules that support different steps of autophagy [5].One way to dysregulate autophagy is dysregulation of cystatin C (Cys C). This member of the cysteine protease inhibitor superfamily 2 is expressed in all eukaryotic cells, and it protects cells from inappropriate proteolysis [6]. Deficiency of Cys C in apoE -/mice disrupts autophagy and induces macrophage apoptosis [7]. Conversely, Cys C-mediated activation of autophagy in neurons prevents

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“…Inflammation is critical for initiating tissue repair, maintaining basal cognitive and homeostatic functions; however, sustained neuroinflammation has injurious effects on neurological function, disrupting cognition, and promoting neurodegeneration [22,23]. Inflammatory cytopathology includes microglial and astrocytic reactions [24]. Microglia, the resident macrophage population of the central nervous system, play a major role in this neuroinflammation [25,26].…”

Section: Neuroinflammationmentioning

confidence: 99%

Magnetic Resonance Texture Analysis in Alzheimer's disease

Cai

Zhong

et al. 2020

Academic Radiology

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Texture analysis is an emerging field that allows mathematical detection of changes in MRI signals that are not visible among image pixels. Alzheimer's disease, a progressive neurodegenerative disease, is the most common cause of dementia. Recently, multiple texture analysis studies in patients with Alzheimer's disease have been performed. This review summarizes the main contributors to Alzheimer's disease-associated cognitive decline, presents a brief overview of texture analysis, followed by review of various MR imaging texture analysis applications in Alzheimer's disease. We also discuss the current challenges for widespread clinical utilization. MR texture analysis could potentially be applied to develop neuroimaging biomarkers for use in Alzheimer's disease clinical trials and diagnosis.

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An update on the interactions between Alzheimer's disease, autophagy and inflammation

Cited by 67 publications

References 167 publications

p62/SQSTM1 accumulation due to degradation inhibition and transcriptional activation plays a critical role in silica nanoparticle-induced airway inflammation via NF-κB activation

p62/SQSTM1 accumulation due to degradation inhibition and transcriptional activation plays a critical role in silica nanoparticle-induced airway inflammation via NF-κB activation

Autophagy attenuates postoperative cognitive dysfunction by up-regulating cystatin C in aged rats undergoing splenectomy

Magnetic Resonance Texture Analysis in Alzheimer's disease

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