Cerebral sterile inflammation in neurodegenerative diseases

Otani, Kento; Shichita, Takashi

doi:10.1186/s41232-020-00137-4

Cited by 29 publications

(20 citation statements)

References 101 publications

(98 reference statements)

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“…Both the EOfAD-like and fAI-like mutations caused very statistically significant changes in the gene sets KEGG_CYTOKINE_CYTOKINE_RECEPTOR _INTERACTION and KEGG_RIBOSOME. The former gene set reflects that both mutations appear to affect inflammation that is a characteristic of the pathologies of both EOfAD [93] and fAI (reviewed in [94]). Like oxidative phosphorylation, we have also observed effects on ribosomal protein genes sets for every EOfAD-like mutation we have studied [39][40][41]43].…”

Section: Discussionmentioning

confidence: 99%

PRESENILIN 1 Mutations Causing Early-Onset Familial Alzheimer’s Disease or Familial Acne Inversa Differ in Their Effects on Genes Facilitating Energy Metabolism and Signal Transduction

Barthelson

Dong

Newman

et al. 2021

JAD

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Background: The most common cause of early-onset familial Alzheimer’s disease (EOfAD) is mutations in PRESENILIN 1 (PSEN1) allowing production of mRNAs encoding full-length, but mutant, proteins. In contrast, a single known frameshift mutation in PSEN1 causes familial acne inversa (fAI) without EOfAD. The molecular consequences of heterozygosity for these mutation types, and how they cause completely different diseases, remains largely unexplored. Objective: To analyze brain transcriptomes of young adult zebrafish to identify similarities and differences in the effects of heterozygosity for psen1 mutations causing EOfAD or fAI. Methods: RNA sequencing was performed on mRNA isolated from the brains of a single family of 6-month-old zebrafish siblings either wild type or possessing a single, heterozygous EOfAD-like or fAI-like mutation in their endogenous psen1 gene. Results: Both mutations downregulate genes encoding ribosomal subunits, and upregulate genes involved in inflammation. Genes involved in energy metabolism appeared significantly affected only by the EOfAD-like mutation, while genes involved in Notch, Wnt and neurotrophin signaling pathways appeared significantly affected only by the fAI-like mutation. However, investigation of direct transcriptional targets of Notch signaling revealed possible increases in γ-secretase activity due to heterozygosity for either psen1 mutation. Transcriptional adaptation due to the fAI-like frameshift mutation was evident. Conclusion: We observed both similar and contrasting effects on brain transcriptomes of the heterozygous EOfAD-like and fAI-like mutations. The contrasting effects may illuminate how these mutation types cause distinct diseases.

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Section: Discussionmentioning

confidence: 99%

PRESENILIN 1 Mutations Causing Early-Onset Familial Alzheimer’s Disease or Familial Acne Inversa Differ in Their Effects on Genes Facilitating Energy Metabolism and Signal Transduction

Barthelson

Dong

Newman

et al. 2021

JAD

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“…Brain aging is related to immunosenescence and low-grade inflammation (inflammaging), to which activated macrophages and monocytes will contribute and promote neuroinflammation, a key event in chronic age-related neurodegenerative diseases [ 524 , 525 ]. Similarly, systemic inflammation is also a predictor of brain aging [ 526 , 527 ].…”

Section: Apoe In Alzheimer’s Diseasementioning

confidence: 99%

APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

Fernández-Calle

Konings

Frontiñán-Rubio

et al. 2022

Mol Neurodegeneration

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ApoE is the major lipid and cholesterol carrier in the CNS. There are three major human polymorphisms, apoE2, apoE3, and apoE4, and the genetic expression of APOE4 is one of the most influential risk factors for the development of late-onset Alzheimer's disease (AD). Neuroinflammation has become the third hallmark of AD, together with Amyloid-β plaques and neurofibrillary tangles of hyperphosphorylated aggregated tau protein. This review aims to broadly and extensively describe the differential aspects concerning apoE. Starting from the evolution of apoE to how APOE's single-nucleotide polymorphisms affect its structure, function, and involvement during health and disease. This review reflects on how APOE's polymorphisms impact critical aspects of AD pathology, such as the neuroinflammatory response, particularly the effect of APOE on astrocytic and microglial function and microglial dynamics, synaptic function, amyloid-β load, tau pathology, autophagy, and cell–cell communication. We discuss influential factors affecting AD pathology combined with the APOE genotype, such as sex, age, diet, physical exercise, current therapies and clinical trials in the AD field. The impact of the APOE genotype in other neurodegenerative diseases characterized by overt inflammation, e.g., alpha- synucleinopathies and Parkinson's disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis, and multiple sclerosis, is also addressed. Therefore, this review gathers the most relevant findings related to the APOE genotype up to date and its implications on AD and CNS pathologies to provide a deeper understanding of the knowledge in the APOE field.

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“…Recent studies have shown that the disruption of the balance between anti-inflammatory and pro-inflammatory signals in the brain tissue of AD patients leads to chronic neuroinflammation, which is associated with activated microglia and the release of various cytokines ( Sonninen et al, 2020 ; Yang and Zhang, 2020 ). Persistent immune/inflammatory responses in the brain are not only associated with neuronal loss and neurodegeneration but are also closely related to the initial Aβ pathology and its interaction with NFTs ( Otani and Shichita, 2020 ). The pathological changes in Aβ and tau in the brain cause excessive activation of astrocytes and microglia, express a large number of inflammatory substances, and produce an excessively sustained chronic inflammatory response, which leads to neuronal dysfunction, degeneration, and apoptosis ( Calsolaro and Edison, 2016 ; Zhou et al, 2019 ).…”

Section: Pathological Features Of Alzheimer’s Diseasementioning

confidence: 99%

Cellular Reprogramming and Its Potential Application in Alzheimer’s Disease

Zhou

Zhu

et al. 2022

Front. Neurosci.

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Alzheimer’s disease (AD) has become the most common age-related dementia in the world and is currently incurable. Although many efforts have been made, the underlying mechanisms of AD remain unclear. Extracellular amyloid-beta deposition, intracellular tau hyperphosphorylation, neuronal death, glial cell activation, white matter damage, blood–brain barrier disruption, and other mechanisms all take part in this complicated disease, making it difficult to find an effective therapy. In the study of therapeutic methods, how to restore functional neurons and integrate myelin becomes the main point. In recent years, with the improvement and maturity of induced pluripotent stem cell technology and direct cell reprogramming technology, it has become possible to induce non-neuronal cells, such as fibroblasts or glial cells, directly into neuronal cells in vitro and in vivo. Remarkably, the induced neurons are functional and capable of entering the local neural net. These encouraging results provide a potential new approach for AD therapy. In this review, we summarized the characteristics of AD, the reprogramming technique, and the current research on the application of cellular reprogramming in AD. The existing problems regarding cellular reprogramming and its therapeutic potential for AD were also reviewed.

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Cerebral sterile inflammation in neurodegenerative diseases

Cited by 29 publications

References 101 publications

PRESENILIN 1 Mutations Causing Early-Onset Familial Alzheimer’s Disease or Familial Acne Inversa Differ in Their Effects on Genes Facilitating Energy Metabolism and Signal Transduction

PRESENILIN 1 Mutations Causing Early-Onset Familial Alzheimer’s Disease or Familial Acne Inversa Differ in Their Effects on Genes Facilitating Energy Metabolism and Signal Transduction

APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

Cellular Reprogramming and Its Potential Application in Alzheimer’s Disease

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