Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?

Nature Reviews Neurology, Journal Year: 2020, Volume and Issue: 17(3), P. 157 - 172

Published: Dec. 14, 2020

Language: Английский

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Selective autophagy of intracellular organelles: Recent research advances

Theranostics, Journal Year: 2020, Volume and Issue: 11(1), P. 222 - 256

Published: Oct. 9, 2020

Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the lysosomal system (the vacuole in plants yeast). Autophagy generally induced by stress, such as oxygen-, energy- amino acid-deprivation, irradiation, drugs, etc. In addition to non-selective bulk degradation, autophagy also occurs selective manner, recycling specific mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes lipid droplets (LDs). This capability makes major maintaining cellular homeostasis. The dysfunction of implicated neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure, Considering importance cell biology, we systemically review recent advances our understanding this its regulatory mechanisms. We emphasize 'cargo-ligand-receptor' model for organelles components yeast mammals, with focus on mitophagy ER-phagy, which are finely described types autophagy. Additionally, highlight unanswered questions field, helping readers research blind spots need be broken.

Language: Английский

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Mild Cognitive Impairment in Clinical Practice: A Review Article

American Journal of Alzheimer s Disease & Other Dementias®, Journal Year: 2018, Volume and Issue: 33(8), P. 500 - 507

Published: Aug. 1, 2018

The spectrum of cognitive decline in the elderly ranges from what can be classified as normal with aging to subjective impairment mild (MCI) dementia. This article reviewed up-to-date evidence MCI including diagnostic criteria due Alzheimer’s disease, vascular and Parkinson management preventive intervention MCI. There are various etiologies MCI, a large number studies have been conducted ascertain practical modalities preserving cognition predementia stages. Lifestyle modification, such aerobic exercise, is an approved modality preserve ability decrease rate progression dementia, well being recommended for frailty prevention.

Language: Английский

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The relationship between autophagy and the immune system and its applications for tumor immunotherapy

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: Jan. 24, 2019

Autophagy is a genetically well-controlled cellular process that tightly controlled by set of core genes, including the family autophagy-related genes (ATG). "double-edged sword" in tumors. It can promote or suppress tumor development, which depends on cell and tissue types stages tumor. At present, immunotherapy promising treatment strategy against Recent studies have shown autophagy significantly controls immune responses modulating functions cells production cytokines. Conversely, some cytokines great effect function autophagy. Therapies aiming at to enhance anti-tumor effects become prospective strategy, with enhanced antigen presentation higher sensitivity CTLs. However, induction may also benefit escape from surveillance result intrinsic resistance immunotherapy. Increasing proven optimal use either ATG inducers inhibitors restrain growth progression enhancing overcoming combination several immunotherapeutic strategies, indicating inhibition might show us therapeutic when combined In this article, possible mechanisms regulating system, potential applications will be discussed.

Language: Английский

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Autophagy in the renewal, differentiation and homeostasis of immune cells

Nature reviews. Immunology, Journal Year: 2018, Volume and Issue: 19(3), P. 170 - 183

Published: Dec. 7, 2018

Language: Английский

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Immune dysregulation in amyotrophic lateral sclerosis: mechanisms and emerging therapies

The Lancet Neurology, Journal Year: 2019, Volume and Issue: 18(2), P. 211 - 220

Published: Jan. 18, 2019

Language: Английский

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Epidemiology and treatment of multiple sclerosis in elderly populations

Nature Reviews Neurology, Journal Year: 2019, Volume and Issue: 15(6), P. 329 - 342

Published: April 18, 2019

Language: Английский

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Western diet as a trigger of Alzheimer’s disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 70, P. 101397 - 101397

Published: June 30, 2021

An excess of saturated fatty acids and simple sugars in the diet is a known environmental risk factor Alzheimer's disease (AD) but holistic view interacting processes through which such may contribute to AD pathogenesis missing. We addressed this need extensive analysis published studies investigating effects western (WD) on development humans laboratory animals. reviewed WD-induced systemic alterations comprising metabolic changes, induction obesity adipose tissue inflammation, gut microbiota dysbiosis acceleration low-grade inflammation. Next we provide an overview evidence demonstrating that WD-associated drive impairment blood-brain barrier (BBB) neuroinflammation paralleled by accumulation toxic amyloid. Later these changes are followed dysfunction synaptic transmission, neurodegeneration finally memory cognitive impairment. conclude WD can trigger inflammaging, BBB induced inflammation play central role process. Moreover, concurrence Aβ dyshomeostasis, reciprocal interactions vicious cycle neurodegeneration, contradicts as primary AD. Given 2019 World Health Organization recommended focusing modifiable factors prevention, sequential, complex pathomechanisms initiated WD, lead from peripheral disturbances support future prevention strategies.

Language: Английский

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The Dual Role of Microglia in ALS: Mechanisms and Therapeutic Approaches

Frontiers in Aging Neuroscience, Journal Year: 2017, Volume and Issue: 9

Published: July 24, 2017

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by non-cell autonomous motor neuron loss. While it generally believed that the onset takes place inside neurons, different cell types mediating neuroinflammatory processes are considered deeply involved in progression of disease. On these grounds, many treatments have been tested on ALS animals with aim inhibiting or reducing pro-inflammatory action microglia and astrocytes counteract Unfortunately, anti-inflammatory therapies only modestly successful. The non-univocal role played during stress injuries might explain this failure. Indeed, now well recognized that, ALS, displays phenotypes, from surveillant early stages, to activated states, M1 M2, expression respectively harmful protective genes later phases Consistently, inhibition microglial function seems be valid strategy if stages polarization taken into account, interfering reactivity specifically targeting pathways and/or potentiating trophic ones. In review, we will analyze features timing activation light M1/M2 phenotypes main mice models ALS. Moreover, also revise results obtained aimed unbalance ratio, shifting towards outcome.

Language: Английский

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TLR4 (toll-like receptor 4) activation suppresses autophagy through inhibition of FOXO3 and impairs phagocytic capacity of microglia

Autophagy, Journal Year: 2018, Volume and Issue: 15(5), P. 753 - 770

Published: Dec. 7, 2018

Macroautophagy/autophagy is a lysosome-dependent catabolic process for the turnover of proteins and organelles in eukaryotes. Autophagy plays an important role immunity inflammation, as well metabolism cell survival. Diverse immune inflammatory signals induce autophagy macrophages through pattern recognition receptors, such toll-like receptors (TLRs). However, physiological its signaling mechanisms microglia remain poorly understood. Microglia are phagocytic cells that resident central nervous system share many characteristics with macrophages. Here, we show autophagic flux expression autophagy-related (Atg) genes significantly suppressed upon TLR4 activation by lipopolysaccharide (LPS), contrast to their stimulation LPS Metabolomics analysis levels phosphatidylinositol (PtdIns) 3-phosphorylated form, PtdIns3P, combination bioinformatics prediction, revealed LPS-induced reduction synthesis PtdIns PtdIns3P but not Interestingly, inhibition PI3K, MTOR or MAPK1/3, restored concomitant dephosphorylation nuclear translocation FOXO3. A constitutively active form FOXO3 also induced autophagy, suggesting downstream target PI3K pathway inhibition. treatment impaired capacity microglia, including MAP1LC3B/LC3-associated phagocytosis (LAP) amyloid β (Aβ) clearance. LAP degradation against Aβ. These findings suggest unique mechanism regulation microglial point PI3K-FOXO3 potential therapeutic regulate function brain disorders.Abbreviations: Atg: gene; Aβ: amyloid-β; BafA1: bafilomycin A1; BECN1: beclin 1, related; BMDM: bone marrow-derived macrophage; CA: active; CNS: system; ZFYVE1/DFCP1: zinc finger, FYVE domain containing 1; FOXO: forkhead box O; ELISA:enzyme-linked immunosorbent assay; HBSS: Hanks balanced salt solution; LAP: LC3-associated phagocytosis; MAP1LC3B: microtubule-associated protein 1 light chain 3; LPS: lipopolysaccharide; LY: LY294002; MTOR: mechanistic rapamycin kinase; Pam3CSK4: N-palmitoyl-S-dipalmitoylglyceryl Cys-Ser-(Lys)4; PtdIns: phosphatidylinositol; PtdIns3P: phosphatidylinositol-3-phosphate; PLA: proximity ligation Poly(I:C): polyinosinic-polycytidylic acid; qRT-PCR: quantitative real-time polymerase reaction; RPS6KB1: ribosomal S6 kinase, polypeptide TLR: Toll-like receptor; TNF: tumor necrosis factor; TFEB: transcription factor EB; TSPO: translocator protein.

Language: Английский

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