Alzheimer’s Disease-like Early-phase Brain Pathogenesis: Self-curing Amelioration of Neurodegeneration from Pro-inflammatory ‘Wounding’ to Anti-inflammatory ‘Healing’

Jiang, He; Liao, Tao; Zhong, Guoxin; Zhang, Jida; Chen, Yanping; Wang, Qi; Zeng, Quan

doi:10.2174/1567205014666170417111420

Cited by 15 publications

(6 citation statements)

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“…In the present study, we noticed for the first time that CS induces the early-phase and multi-systemic pathogenesis towards dementia, arthritis, tumor and fatty liver by modulating the corresponding hallmarks, i.e., Aβ upregulation for dementia, RF upregulation for arthritis, CD1 upregulation/p21 downregulation for tumor, and NAFLD-related gene overexpression for fatty liver. In particular, a synchronous decline of TH, Ach and ChAT levels was monitored in CS-fed mice, suggesting a hint initiating progressive cognitive deficits seen in LPS-challenged mice [25]. Moreover, arthritis-like erythematous and edematous paws, tumor-like neoplasia and fatty liver-like lipogenesis were also typically observed in CS-fed mice.…”

Section: Discussionmentioning

confidence: 88%

Chondroitin Sulfate Flourishes Gut Sulfatase-Secreting Bacteria To Damage Mucus Layers, Leak Bacterial Debris, And Trigger Inflammatory Lesions In Mice

Liao

Chen

Tan

et al. 2017

Preprint

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Background: An interaction of the food types with the gut microbiota changes is deeply implicated in human health and disease. To verify whether animal-based diets would lead to gut dysbiosis, systemic inflammation and inflammatory pathogenesis, we fed mice with chondroitin sulfate (CS), a sulfate-containing O-glycan naturally occurring in livestock and poultry products, and monitored the dynamic changes of microbial flores, inflammatory signatures, and pathogenic hallmarks. Results: A metagenomic gut microbiota analysis revealed the overgrowth of sulfatasesecreting bacteria and sulfate-reducing bacteria in the gastrointestinal tracts of mice upon daily CS feeding. Sulfatase-secreting bacteria compromise gut integrity through prompting mucin degradation and mucus lesions, which were evident from the upregulation of secretary leukocyte protease inhibitor (SLPI) and mucin 1/4 (MUC-1/4). A synchronous elevation of lipopolysaccharide (LPS) and tumor necrosis factor α (TNF-α) levels in the serum as well as cerebral, hepatic, cardiac and muscular tissues suggests bacterial endotoxinemia, chronic low-grade inflammation and mitochondrial dysfunction, eventually leading to the onset of global inflammatory pathogenesis towards arthritis, dementia, tumor, and fatty liver. Conclusions: CS triggers the early-phase and multi-systemic pathogenesis like arthritis, dementia, tumor, and fatty liver by enhancing gut opportunistic infection and evoking low-grade inflammation in mice. A plausible reason for the inconsistency of CS in treatment of osteoarthritis (OA) was also discussed.

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Section: Discussionmentioning

confidence: 88%

Chondroitin Sulfate Flourishes Gut Sulfatase-Secreting Bacteria To Damage Mucus Layers, Leak Bacterial Debris, And Trigger Inflammatory Lesions In Mice

Liao

Chen

Tan

et al. 2017

Preprint

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“…As alluded to earlier, altered protein and activity have been reported in both PD and AD. This can occur in several ways such as degeneration of LC noradrenergic neurons, neuroinflammation, and dysregulation of copper levels that are all associated with both neurological diseases (McMillan et al ; Trillo et al ; He et al ; Tang et al ; Peterson and Li ; Ross et al ).…”

Section: Dβh In Neurodegenerative Diseasementioning

confidence: 99%

Dopamine beta‐hydroxylase and its genetic variants in human health and disease

Gonzalez-Lopez

Vrana

2019

Journal of Neurochemistry

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Dopamine beta-hydroxylase (DbH) is an essential neurotransmitter-synthesizing enzyme that catalyzes the formation of norepinephrine (NE) from dopamine and has been extensively studied since its discovery in the 1950s. NE serves as a neurotransmitter in both the central and peripheral nervous systems and is the precursor to epinephrine synthesis in the brain and adrenal medulla. Alterations in noradrenergic signaling have been linked to both central nervous system and peripheral pathologies. DbH protein, which is found in circulation, can, therefore, be evaluated as a marker of norepinephrine function in a plethora of different disorders and diseases. In many of these diseases, DbH protein availability and activity are believed to contribute to disease presentation or select symptomology and are believed to be under strong genetic control. Alteration in the DbH protein by genetic polymorphisms may result in DbH becoming ratelimiting and directly contributing to lower NE and epinephrine levels and disease. With the completion of the human genome project and the advent of next-generation sequencing, new insights have been gained into the existence of naturally occurring DbH sequencing variants (genetic polymorphisms) in disease. Also, biophysical tools coupled with genetic sequences are illuminating structure-function relationships within the enzyme. In this review, we discuss the role of genetic variants in DbH and its role in health and disease.

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“…For instance, it has been demonstrated that blocking the signaling pathway of IL-1β can ameliorate the pathology of CNS in mouse models with AD (122,126). In addition, a new study has verified that administration of TNF-α monoclonal antibody (infliximab) of AD or regulating glucose metabolism can reduce amyloid plaques and phospho-tau (127). Restricting the priming and overactivation of microglia can be a powerful targeting method to treat AD.…”

Section: Therapeutic Interventionsmentioning

confidence: 99%

Microglial priming in Alzheimer’s disease

Zong

Cao

et al. 2018

Ann. Transl. Med.

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Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease of central nervous system (CNS). Nowadays, increasing evidence suggests that immune system plays a significant role in the mechanisms of AD's onset and progression. Microglia, the main participator in the immune system of CNS, is always regarded as a protector of our brain in a healthy state and also has a beneficial role in maintaining the homeostasis of CNS microenvironment. However, chronic and sustained stimulation can push microglia into the state termed priming. Primed microglia can induce the production of amyloid β (Aβ), tau pathology, neuroinflammation and reduce the release of neurotrophic factors, resulting in loss of normal neurons in quantity and function that has immense relationship with AD. The therapeutic strategies mainly aimed at modulating the microenvironment and microglial activity in CNS to delay progression and alleviate pathogenesis of AD. Overall, in this review, we highlight the mechanism of microglial priming, and discuss the profound relationship between microglial priming and AD. Besides, we also pay attention to the therapeutic strategies targeting at microglial priming.

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Alzheimer’s Disease-like Early-phase Brain Pathogenesis: Self-curing Amelioration of Neurodegeneration from Pro-inflammatory ‘Wounding’ to Anti-inflammatory ‘Healing’

Abstract: Conclusively, EA initially aggravates and subsequently ameliorates CC-evoked AD-like earlyphase brain pathogenesis via conversion from pro-inflammatory microglia to anti-inflammatory microglia.

Cited by 15 publications

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Chondroitin Sulfate Flourishes Gut Sulfatase-Secreting Bacteria To Damage Mucus Layers, Leak Bacterial Debris, And Trigger Inflammatory Lesions In Mice

Chondroitin Sulfate Flourishes Gut Sulfatase-Secreting Bacteria To Damage Mucus Layers, Leak Bacterial Debris, And Trigger Inflammatory Lesions In Mice

Dopamine beta‐hydroxylase and its genetic variants in human health and disease

Microglial priming in Alzheimer’s disease

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