Functional insight into LOAD-associated microglial response genes

Jonas, Lauren A.; Jain, Tanya; Li, Yueming

doi:10.1098/rsob.210280

Cited by 7 publications

(2 citation statements)

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“…Mounting evidence from animal models has demonstrated that microglia are closely involved in AD pathological development as a double‐edged sword: microglia migrate to early forming plaques in Tg mice (Meyer‐Luehmann et al, 2008) and have the capability of phagocytosing APP derived peptides (Yamanaka et al, 2012), while Aβ‐stimulated microglia can secrete high levels of cytokines and actively strip synapses, which contributes to the loss of neuronal connection and neurodegeneration (Hong et al, 2016; Wyss‐Coray & Rogers, 2012). Moreover, large‐scale integrative gene network analysis in humans identified microglia and immune‐specific modules as highly relevant to late‐onset AD (Jonas et al, 2022; Zhang et al, 2013). Among the 20+ AD‐associated gene variants pinpointed by Genome‐Wide Association Studies (GWAS), a majority were expressed by microglia (Villegas‐Llerena et al, 2016).…”

Section: The Role Of β‐Ar In Admentioning

confidence: 99%

The β‐adrenergic hypothesis of synaptic and microglial impairment in Alzheimer's disease

2023

Journal of Neurochemistry

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Alzheimer's disease (AD) is a progressive neurodegenerative disease originating partly from amyloid β protein‐induced synaptic failure. As damaging of noradrenergic neurons in the locus coeruleus (LC) occurs at the prodromal stage of AD, activation of adrenergic receptors could serve as the first line of defense against the onset of the disease. Activation of β2‐ARs strengthens long‐term potentiation (LTP) and synaptic activity, thus improving learning and memory. Physical stimulation of animals exposed to an enriched environment (EE) leads to the activation of β2‐ARs and prevents synaptic dysfunction. EE also suppresses neuroinflammation, suggesting that β2‐AR agonists may play a neuroprotective role. The β2‐AR agonists used for respiratory diseases have been shown to have an anti‐inflammatory effect. Epidemiological studies further support the beneficial effects of β2‐AR agonists on several neurodegenerative diseases. Thus, I propose that β2‐AR agonists may provide therapeutic value in combination with novel treatments for AD.

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Section: The Role Of β‐Ar In Admentioning

confidence: 99%

The β‐adrenergic hypothesis of synaptic and microglial impairment in Alzheimer's disease

2023

Journal of Neurochemistry

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“…The hMSC (Human mesenchymal stem cell) therapy considerably reduced LPS-induced microglial activation, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS) mRNA phrase, and also the creation of NO compared to the LPS-only therapy. MSCs might directly or indirectly control the condition of astrocytes or microglia and rely on TFs signifying paths to readjust the equilibrium of inflammatory cytokines, consisting of each pro-inflammatory and anti-inflammatory cytokines 62,64 . Nevertheless, the underlying systems of MSC treatment for AD stay uncertain.…”

Section: How Mesenchymal Stem Cells Play Its Role Inmentioning

confidence: 99%

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2022

IJPSR

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Mesenchymal Stem Cells are multipotent adult stem cells that are found in tissues of the body, including umbilical lines, bone marrow, fat cells, etc. Mesenchymal stem cells incline to self-restore tissues, such as bone, fat cells, connective tissues, and microglia cells, which are obtained from the mesoderm layer and act as macrophages in the central nervous system. So, MSCs can be used to promote functional recovery in many neurological disorders. Neuroinflammation is a pathological feature of neurodegenerative diseases, which is also indicated to mediate neuronal damage and deteriorate the backward accumulation of Aβ in Alzheimer's disease. The mechanism for MSC-based therapy in Alzheimer's disease that MSCs regulate neuroinflammation by microglia activation; this will reduce pathological features such as tau hyperphosphorylation and Aβ deposits and save the spatial learning and memory deficits and their multipotentiality and secretome, based on these findings include cell therapy methods for Parkinson disease mainly focused on the ability of stem cells to differentiate into Dopaminergic neurons producing cells that will replace diseased Dopaminergic neurons. MSC-based therapeutics have been suggested for osteoarthritis. MSCs were mostly found in a thin layer of connective tissue called periosteum, lungs, milk teeth, tendon, synovial stratum, cancellous bone, adipose tissue, tendon, lung, and other tissues. MSCs associated with immune cells and have immunomodulatory effects. Moreover, the RAP1/NFkb signalling pathway controls MSC paracrine activity, which seems to be linked with Female infertility. This review will assist you in understanding many aspects of MSC and its molecular role and therapeutic applications.

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