Recent Insights on the Role of PPAR-β/δ in Neuroinflammation and Neurodegeneration, and Its Potential Target for Therapy DOI Creative Commons
Anna K. Strosznajder, Sylwia Wójtowicz,

Mieszko J. Jeżyna

et al.

NeuroMolecular Medicine, Journal Year: 2020, Volume and Issue: 23(1), P. 86 - 98

Published: Nov. 18, 2020

Abstract Peroxisome proliferator-activated receptor (PPAR) β/δ belongs to the family of hormone and lipid-activated nuclear receptors, which are involved in metabolism long-chain fatty acids, cholesterol, sphingolipids. Similar PPAR-α PPAR-γ, PPAR-β/δ also acts as a transcription factor activated by dietary lipids endogenous ligands, such saturated polyunsaturated selected lipid metabolic products, eicosanoids, leukotrienes, lipoxins, hydroxyeicosatetraenoic acids. Together with other PPARs, displays transcriptional activity through interaction retinoid X (RXR). In general, PPARs have been shown regulate cell differentiation, proliferation, development significantly modulate glucose, metabolism, mitochondrial function, biogenesis. appears play special role inflammatory processes due its proangiogenic anti-/pro-carcinogenic properties, this has considered therapeutic target for treating syndrome, dyslipidemia, carcinogenesis, diabetes. Until now, most studies were carried out peripheral organs, despite presence brain cells different regions, neurodegeneration neuroinflammation remains poorly understood. This review is intended describe recent insights on impact novel agonists neurodegenerative disorders, including Alzheimer’s Parkinson’s, Huntington’s diseases, multiple sclerosis, stroke, traumatic injury. An important goal obtain new better understand pharmacological regulations find promising strategies that could mitigate these neurological disorders.

Language: Английский

Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson’s disease DOI Creative Commons
Velma T. E. Aho, Madelyn C. Houser, Pedro A. B. Pereira

et al.

Molecular Neurodegeneration, Journal Year: 2021, Volume and Issue: 16(1)

Published: Feb. 8, 2021

Abstract Background Previous studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson’s disease (PD), but how these factors linked they contribute to processes symptoms remains uncertain. This study sought compare identify associations among PD patients controls elucidate their interrelations links clinical manifestations of PD. Methods Stool plasma samples data were collected from 55 56 controls. Levels stool SCFAs inflammatory permeability markers compared between related one another the microbiota. Results Calprotectin was increased decreased a sex-dependent manner. Inflammatory neither intercorrelated nor strongly associated with SCFA levels. Age at onset positively correlated negatively CXCL8 IL-1β stool. Fecal zonulin fecal NGAL motor non-motor symptoms. Microbiota diversity composition levels SCFAs, factors, Certain relationships differed by sex. Conclusions Intestinal responses reductions occur PD, microbiota onset, not reflected profiles. Some distinct sex-dependent. revealed potential alterations microbiota-host interactions earlier intestinal reduced levels, highlighting candidate molecules pathways which may pathogenesis presentation warrant further investigation.

Language: Английский

Citations

310
Western diet as a trigger of Alzheimer’s disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration DOI Creative Commons
Angelika Więckowska‐Gacek, Anna Mietelska‐Porowska, Małgorzata Wydrych

et al.

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

Citations

237
Gut Bacteria and Neurotransmitters DOI Creative Commons
Leon M. T. Dicks

Microorganisms, Journal Year: 2022, Volume and Issue: 10(9), P. 1838 - 1838

Published: Sept. 14, 2022

Gut bacteria play an important role in the digestion of food, immune activation, and regulation entero-endocrine signaling pathways, but also communicate with central nervous system (CNS) through production specific metabolic compounds, e.g., bile acids, short-chain fatty acids (SCFAs), glutamate (Glu), γ-aminobutyric acid (GABA), dopamine (DA), norepinephrine (NE), serotonin (5-HT) histamine. Afferent vagus nerve (VN) fibers that transport signals from gastro-intestinal tract (GIT) gut microbiota to brain are linked receptors esophagus, liver, pancreas. In response these stimuli, sends back entero-epithelial cells via efferent VN fibers. Fibers not direct contact wall or intestinal microbiota. Instead, reach 100 500 million neurons enteric (ENS) submucosa myenteric plexus wall. The modulation, development, renewal ENS controlled by microbiota, especially those ability produce metabolize hormones. Signals generated hypothalamus pituitary adrenal glands hypothalamic axis (HPA). SCFAs produced adhere free (FFARs) on surface epithelial (IECs) interact enter circulatory system. alter synthesis degradation neurotransmitters. This review focuses effect have neurotransmitters vice versa.

Language: Английский

Citations

213
Microglial phagocytosis of neurons in neurodegeneration, and its regulation DOI
Claire A. Butler, Alma S. Popescu, Emily J. A. Kitchener

et al.

Journal of Neurochemistry, Journal Year: 2021, Volume and Issue: 158(3), P. 621 - 639

Published: Feb. 20, 2021

There is growing evidence that excessive microglial phagocytosis of neurons and synapses contributes to multiple brain pathologies. RNA-seq genome-wide association (GWAS) studies have linked phagocytic genes neurodegenerative diseases, knock-out has been found protect against neurodegeneration in animal models, suggesting neurodegeneration. Here, we review recent live causes models Alzheimer's disease other tauopathies, Parkinson's disease, frontotemporal dementias, sclerosis, retinal degeneration induced by ischaemia, infection or ageing. We also factors regulating neurons, including: nucleotides, frackalkine, phosphatidylserine, calreticulin, UDP, CD47, sialylation, complement, galectin-3, Apolipoprotein E, receptors, Siglec cytokines, epigenetics expression profile. Some these may be potential treatment targets prevent mediated synapses.

Language: Английский

Citations

195
Gut microbiota modulates the inflammatory response and cognitive impairment induced by sleep deprivation DOI
Zhong Wang,

Wen‐Hao Chen,

Su‐Xia Li

et al.

Molecular Psychiatry, Journal Year: 2021, Volume and Issue: 26(11), P. 6277 - 6292

Published: May 7, 2021

Language: Английский

Citations

181
The Role of Lipopolysaccharide-Induced Cell Signalling in Chronic Inflammation DOI Creative Commons
Martin Pagé, Douglas B. Kell, Etheresia Pretorius

et al.

Chronic Stress, Journal Year: 2022, Volume and Issue: 6

Published: Jan. 1, 2022

Lipopolysaccharide (LPS) is the main structural component of outer membrane most Gram-negative bacteria and has diverse immunostimulatory procoagulant effects. Even though LPS well described for its role in pathology sepsis, considerable evidence demonstrates that LPS-induced signalling immune dysregulation are also relevant pathophysiology many diseases, characteristically where endotoxaemia less severe. These diseases typically chronic progressive nature span broad classifications, including neurodegenerative, metabolic, cardiovascular diseases. This Review reappraises mechanisms emphasises crucial contribution to multiple beyond conventional sepsis. perspective asserts new ways approaching by targeting LPS-driven pathways may be therapeutic benefit a wide range inflammatory conditions.

Language: Английский

Citations

172
Inflammatory pathways in Alzheimer’s disease mediated by gut microbiota DOI
Xiaohang Qian,

Xiaoxuan Song,

Xiaoli Liu

et al.

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 68, P. 101317 - 101317

Published: March 10, 2021

Language: Английский

Citations

119
The amyloid cascade hypothesis: an updated critical review DOI
Kasper P. Kepp,

Nikolaos K. Robakis,

Poul Flemming Høilund‐Carlsen

et al.

Brain, Journal Year: 2023, Volume and Issue: 146(10), P. 3969 - 3990

Published: May 15, 2023

Results from recent clinical trials of antibodies that target amyloid-β (Aβ) for Alzheimer's disease have created excitement and been heralded as corroboration the amyloid cascade hypothesis. However, while Aβ may contribute to disease, genetic, clinical, imaging biochemical data suggest a more complex aetiology. Here we review history weaknesses hypothesis in view new evidence obtained anti-amyloid antibodies. These indicate treatments either no or uncertain effect on cognition. Despite importance definition argue point playing minor aetiological role. We also discuss suggesting concerted activity many pathogenic factors propose evolving multi-factor models will better underpin search effective strategies treat disease.

Language: Английский

Citations

111
Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease DOI Creative Commons

Manlian Zhu,

Xia Liu, Yiru Ye

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: June 24, 2022

Parkinson’s disease (PD) is the second most common neurodegenerative characterized by motor dysfunction. Growing evidence has demonstrated that gut dysbiosis involved in occurrence, development and progression of PD. Numerous clinical trials have identified characteristics changed microbiota profiles, preclinical studies PD animal models indicated can influence onset via increasing intestinal permeability, aggravating neuroinflammation, aggregating abnormal levels α-synuclein fibrils, oxidative stress, decreasing neurotransmitter production. The be considered promising diagnostic therapeutic targets for PD, which regulated probiotics, psychobiotics, prebiotics, synbiotics, postbiotics, fecal transplantation, diet modifications, Chinese medicine. This review summarizes recent PD-associated profiles functions, potential roles, mechanisms microbiota-targeted interventions Deciphering underlying roles will help interpret pathogenesis from new perspectives elucidate novel strategies

Language: Английский

Citations

107
Mechanisms and pathology of protein misfolding and aggregation DOI
Nikolaos Louros, Joost Schymkowitz, Frédéric Rousseau

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(12), P. 912 - 933

Published: Sept. 8, 2023

Language: Английский

Citations

105