scholarly journals Triggering Innate Immune Receptors as New Therapies in Alzheimer’s Disease and Multiple Sclerosis

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2164
Author(s):  
Pierre-Alexandre Piec ◽  
Vincent Pons ◽  
Serge Rivest
Keyword(s):  
Multiple Sclerosis ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Innate Immunity ◽  
Immune Cells ◽  
Therapeutic Potential ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Disease Course ◽  
Beneficial Effects

Multiple sclerosis and Alzheimer’s disease are two complex neurodegenerative diseases involving the immune system. So far, available treatments provide at best mild improvements to patients’ conditions. For decades now, a new set of molecules have been used to modulate and regulate the innate immunity in these pathologies. Most studies have been carried out in rodents and some of them have reported tremendous beneficial effects on the disease course. The modulation of innate immune cells is of great interest since it provides new hope for patients. In this review, we will briefly overview the therapeutic potential of some molecules and receptors in multiple sclerosis and Alzheimer’s disease and how they could be used to exploit new therapeutic avenues.

scholarly journals Immunohistochemical Study of ASC Expression and Distribution in the Hippocampus of an Aged Murine Model of Alzheimer’s Disease

2021 ◽  
Vol 22 (16) ◽  
pp. 8697
Author(s):  
Diana Reimers ◽  
Manuela Vallejo-Muñoz ◽  
María José Casarejos ◽  
Adriano Jimenez-Escrig ◽  
Rafael Gonzalo-Gobernado ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Cells ◽  
Immunohistochemical Study ◽  
Transgenic Mouse Model ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Danger Signals ◽  
Model Of Alzheimer’S Disease ◽  
Pro Inflammatory Cytokines

Neuroinflammation is involved in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD), and is notably dependent on age. One important inflammatory pathway exerted by innate immune cells of the nervous system in response to danger signals is mediated by inflammasomes (IF) and leads to the generation of potent pro-inflammatory cytokines. The protein “apoptosis-associated speck-like protein containing a caspase recruitment domain” (ASC) modulates IF activation but has also other functions which are crucial in AD. We intended to characterize immunohistochemically ASC and pattern recognition receptors (PRR) of IF in the hippocampus (HP) of the transgenic mouse model Tg2576 (APP), in which amyloid-beta (Aβ) pathology is directly dependent on age. We show in old-aged APP a significant amount of ASC in microglia and astrocytes associated withAβ plaques, in the absence of PRR described by others in glial cells. In addition, APP developed foci with clusters of extracellular ASC granules not spatiallyrelated to Aβ plaques, which density correlated with the advanced age of mice and AD development. Clusters were associated withspecific astrocytes characterized by their enlarged ring-shaped process terminals, ASC content, and frequent perivascular location. Their possible implication in ASC clearance and propagation of inflammation is discussed.

scholarly journals Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau

2018 ◽  
Vol 215 (9) ◽  
pp. 2235-2245 ◽  
Author(s):  
Silvia S. Kang ◽  
Mark T.W. Ebbert ◽  
Kelsey E. Baker ◽  
Casey Cook ◽  
Xuewei Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disease ◽  
Immune Cells ◽  
Cell Sorting ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Potential Mechanism ◽  
The Brain

Alzheimer’s disease (AD) is an age-associated neurodegenerative disease characterized by amyloidosis, tauopathy, and activation of microglia, the brain resident innate immune cells. We show that a RiboTag translational profiling approach can bypass biases due to cellular enrichment/cell sorting. Using this approach in models of amyloidosis, tauopathy, and aging, we revealed a common set of alterations and identified a central APOE-driven network that converged on CCL3 and CCL4 across all conditions. Notably, aged females demonstrated a significant exacerbation of many of these shared transcripts in this APOE network, revealing a potential mechanism for increased AD susceptibility in females. This study has broad implications for microglial transcriptomic approaches and provides new insights into microglial pathways associated with different pathological aspects of aging and AD.

scholarly journals The cell biology of inflammation: From common traits to remarkable immunological adaptations

2020 ◽  
Vol 219 (7) ◽  
Author(s):  
Helen Weavers ◽  
Paul Martin
Keyword(s):  
Innate Immunity ◽  
Cell Division ◽  
Membrane Trafficking ◽  
Immune Cells ◽  
Cell Biology ◽  
Foreign Bodies ◽  
Cell Types ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Starting Point

Tissue damage triggers a rapid and robust inflammatory response in order to clear and repair a wound. Remarkably, many of the cell biology features that underlie the ability of leukocytes to home in to sites of injury and to fight infection—most of which are topics of intensive current research—were originally observed in various weird and wonderful translucent organisms over a century ago by Elie Metchnikoff, the “father of innate immunity,” who is credited with discovering phagocytes in 1882. In this review, we use Metchnikoff’s seminal lectures as a starting point to discuss the tremendous variety of cell biology features that underpin the function of these multitasking immune cells. Some of these are shared by other cell types (including aspects of motility, membrane trafficking, cell division, and death), but others are more unique features of innate immune cells, enabling them to fulfill their specialized functions, such as encapsulation of invading pathogens, cell–cell fusion in response to foreign bodies, and their self-sacrifice as occurs during NETosis.

scholarly journals Stress Hyperglycemia, Insulin Treatment, and Innate Immune Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Fangming Xiu ◽  
Mile Stanojcic ◽  
Li Diao ◽  
Marc G. Jeschke
Keyword(s):  
Insulin Resistance ◽  
Innate Immunity ◽  
Immune System ◽  
Critical Illness ◽  
Immune Cells ◽  
Innate Immune System ◽  
Insulin Treatment ◽  
Innate Immune ◽  
Morbidity And Mortality ◽  
Innate Immune Cells

Hyperglycemia (HG) and insulin resistance are the hallmarks of a profoundly altered metabolism in critical illness resulting from the release of cortisol, catecholamines, and cytokines, as well as glucagon and growth hormone. Recent studies have proposed a fundamental role of the immune system towards the development of insulin resistance in traumatic patients. A comprehensive review of published literatures on the effects of hyperglycemia and insulin on innate immunity in critical illness was conducted. This review explored the interaction between the innate immune system and trauma-induced hypermetabolism, while providing greater insight into unraveling the relationship between innate immune cells and hyperglycemia. Critical illness substantially disturbs glucose metabolism resulting in a state of hyperglycemia. Alterations in glucose and insulin regulation affect the immune function of cellular components comprising the innate immunity system. Innate immune system dysfunction via hyperglycemia is associated with a higher morbidity and mortality in critical illness. Along with others, we hypothesize that reduction in morbidity and mortality observed in patients receiving insulin treatment is partially due to its effect on the attenuation of the immune response. However, there still remains substantial controversy regarding moderate versus intensive insulin treatment. Future studies need to determine the integrated effects of HG and insulin on the regulation of innate immunity in order to provide more effective insulin treatment regimen for these patients.

scholarly journals Alemtuzumab treatment alters circulating innate immune cells in multiple sclerosis

2016 ◽  
Vol 3 (6) ◽  
pp. e289 ◽  
Author(s):  
Catharina C. Gross ◽  
Diana Ahmetspahic ◽  
Tobias Ruck ◽  
Andreas Schulte-Mecklenbeck ◽  
Kathrin Schwarte ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells

Alzheimer’s Disease Genetics: A Dampened Microglial Response?

2021 ◽  
pp. 107385842110245
Author(s):  
Zena K. Chatila ◽  
Elizabeth M. Bradshaw
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Innate Immune ◽  
Regulatory Mechanisms ◽  
Innate Immune Cells ◽  
Genetic Studies ◽  
Age Related ◽  
Microglial Phenotype ◽  
The Central Nervous System ◽  
Microglial Response

Alzheimer’s disease (AD) is a debilitating age-related neurodegenerative condition. Unbiased genetic studies have implicated a central role for microglia, the resident innate immune cells of the central nervous system, in AD pathogenesis. On-going efforts are clarifying the biology underlying these associations and the microglial pathways that are dysfunctional in AD. Several genetic risk factors converge to decrease the function of activating microglial receptors and increase the function of inhibitory receptors, resulting in a seemingly dampened microglial phenotype in AD. Moreover, many of these microglial proteins that are genetically associated with AD appear to interact and share pathways or regulatory mechanisms, presenting several points of convergence that may be strategic targets for therapeutic intervention. Here, we review some of these studies and their implications for microglial participation in AD pathogenesis.

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