Inflammasome activation in traumatic brain injury and Alzheimer's disease

Johnson, Noye M.; Vaccari, Juan Pablo de Rivero; Bramlett, Helen M.; Keane, Robert W.; Dietrich, W. Dalton

doi:10.1016/j.trsl.2022.08.014

Cited by 41 publications

(21 citation statements)

References 128 publications

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“…A variety of triggers have been associated with AD either as a single event or as multiple events with an accumulation of adverse effects. Some triggering factors that can lead to AD are metals [ 87 ], bacteria [ 88 ], viruses [ 89 ], and physical trauma [ 90 ]. Abnormal nucleolar stress can be a common component in AD onset and progression.…”

Section: Key Players In the Hypothesismentioning

confidence: 99%

Polyamine Dysregulation and Nucleolar Disruption in Alzheimer’s Disease

Brooks

2024

Journal of Alzheimer’s Disease

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A hypothesis of Alzheimer’s disease etiology is proposed describing how cellular stress induces excessive polyamine synthesis and recycling which can disrupt nucleoli. Polyamines are essential in nucleolar functions, such as RNA folding and ribonucleoprotein assembly. Changes in the nucleolar pool of anionic RNA and cationic polyamines acting as counterions can cause significant nucleolar dynamics. Polyamine synthesis reduces S-adenosylmethionine which, at low levels, triggers tau phosphorylation. Also, polyamine recycling reduces acetyl-CoA needed for acetylcholine, which is low in Alzheimer’s disease. Extraordinary nucleolar expansion and/or contraction can disrupt epigenetic control in peri-nucleolar chromatin, such as chromosome 14 with the presenilin-1 gene; chromosome 21 with the amyloid precursor protein gene; chromosome 17 with the tau gene; chromosome 19 with the APOE4 gene; and the inactive X chromosome (Xi; aka “nucleolar satellite”) with normally silent spermine synthase (polyamine synthesis) and spermidine/spermine-N1-acetyltransferase (polyamine recycling) alleles. Chromosomes 17, 19 and the Xi have high concentrations of Alu elements which can be transcribed by RNA polymerase III if positioned nucleosomes are displaced from the Alu elements. A sudden flood of Alu RNA transcripts can competitively bind nucleolin which is usually bound to Alu sequences in structural RNAs that stabilize the nucleolar heterochromatic shell. This Alu competition leads to loss of nucleolar integrity with leaking of nucleolar polyamines that cause aggregation of phosphorylated tau. The hypothesis was developed with key word searches (e.g., PubMed) using relevant terms (e.g., Alzheimer’s, lupus, nucleolin) based on a systems biology approach and exploring autoimmune disease tautology, gaining synergistic insights from other diseases.

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Section: Key Players In the Hypothesismentioning

confidence: 99%

Polyamine Dysregulation and Nucleolar Disruption in Alzheimer’s Disease

Brooks

2024

Journal of Alzheimer’s Disease

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“…Aging leads to profound changes in the immune system, including the activation and dysfunction of microglia in the brain. Specifically, microglia activation undergoes age-related changes in migration and phagocytosis that lead to increased neuroinflammation, white matter damage, and cognitive impairment in older adults and rodents [ 72 , 73 ]. Additionally, aging microglia shift to a proinflammatory state and release TNF-α to upregulate the expression of venous BEC-anchored adhesion molecules (VCAM1 and ICAM1), thereby promoting the transendothelial migration of peripheral T cells [ 74 ].…”

Section: Aging-related Immune System Alterations In Strokementioning

confidence: 99%

Age-Related Alterations in Immune Function and Inflammation: Focus on Ischemic Stroke

2023

Aging dis

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The aging of the global population poses significant scientific challenges. Moreover, the biological process of aging is the most significant risk factor for most chronic illnesses; therefore, understanding the molecular and cellular mechanisms underlying these aging-related challenges is crucial for extending the healthy lifespan of older individuals. Preventing brain aging remains a priority public health goal, and integrative and comprehensive aging analyses have revealed that immunosenescence is a potential cause of age-related brain damage and disease (e.g., stroke). Importantly, the neuroinflammatory and immune systems present two-way contact and thus can affect each other. Emerging evidence supports the numerous effects of immunosenescence- and inflammation-mediated immunity in neurologically injured brains. In this study, we briefly outline how aging alters the pathophysiology and transcriptional amplitude in patients who experienced stroke and then discuss how the immune system and its cellular components and molecular mechanisms are affected by age after stroke. Finally, we highlight emerging interventions with the potential to slow down or reduce aging and prevent stroke onset.

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“…Along with the aforementioned microglia-derived cytokines, neutrophils also induce other molecules to mutually initiate microglia, for instance, lipid carrier protein 2, reactive oxygen species, and MMP9. [13,[115][116][117][118] Activated microglia are beneficial as well as harmful: on 1 hand, it stimulates neutrophils to secrete more pro-inflammatory cytokines, on the other hand, it reduces neuronal damage and the release of microglia neuroprotective factors. [119] However, whether neutrophils affect the M1/M2 polarization of microglia after TBI remains unclear.…”

Section: Microglia Initiation and Neutrophilsmentioning

confidence: 99%

Research progress of neuroinflammation-related cells in traumatic brain injury: A review

Zhao

et al. 2023

Medicine

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Neuroinflammation after traumatic brain injury (TBI) is related to chronic neurodegenerative diseases and is one of the causes of acute secondary injury after TBI. Therefore, it is particularly important to clarify the role of cellular mechanisms in the neuroinflammatory response after TBI. The objective of this article is to understand the involvement of cells during the TBI inflammatory response (for instance, astrocytes, microglia, and oligodendrocytes) and shed light on the recent progress in the stimulation and interaction of granulocytes and lymphocytes, to provide a novel approach for clinical research. We searched articles in PubMed published between 1950 and 2023, using the following keywords: TBI, neuroinflammation, inflammatory cells, neuroprotection, clinical. Articles for inclusion in this paper were finalized based on their novelty, representativeness, and relevance to the main arguments of this review. We found that the neuroinflammatory response after TBI includes the activation of glial cells, the release of inflammatory mediators in the brain, and the recruitment of peripheral immune cells. These inflammatory responses not only induce secondary brain damage, but also have a role in repairing the nervous system to some extent. However, not all of the mechanisms of cell-to-cell interactions have been well studied. After TBI, clinical treatment cannot simply suppress the inflammatory response, and the inflammatory phenotype of patients' needs to be defined according to their specific conditions after injury. Clinical trials of personalized inflammation regulation therapy for specific patients should be carried out in order to improve the prognosis of patients. Abbreviations: AQP4 = aquaporin-4, BBB = blood-brain barrier, CCL21 = chemokine(C-C motif) ligand 21, CNS = central nervous system, CSF = cerebrospinal fluid, CXCL12 = chemokine (C-X-C motif) ligand 12, CXCL1-5 = chemokine(C-X-C motif) ligand 1-5, CXCL8-10 = chemokine(C-X-C motif) ligand 8-10, DAMPs = damage-associated molecular patterns, HMGB1 = high mobility group protein 1, IFN = interferon, IL = interleukin, MMP = matrix metallopeptidase, NF-KB = nuclear factor kappa-B, OPCs = oligodendrocyte progenitor cells, TBI = traumatic brain injury, TNF = tumor necrosis factor.

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Inflammasome activation in traumatic brain injury and Alzheimer's disease

Cited by 41 publications

References 128 publications

Polyamine Dysregulation and Nucleolar Disruption in Alzheimer’s Disease

Polyamine Dysregulation and Nucleolar Disruption in Alzheimer’s Disease

Age-Related Alterations in Immune Function and Inflammation: Focus on Ischemic Stroke

Research progress of neuroinflammation-related cells in traumatic brain injury: A review

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