ICAM-1 protects neurons against Amyloid-β and improves cognitive behaviors in 5xFAD mice by inhibiting NF-κB

Guha, Subhalakshmi; Paidi, Ramesh Kumar; Goswami, Soumita; Saha, Papita; Biswas, Subhas C.

doi:10.1016/j.bbi.2021.11.021

Cited by 16 publications

(11 citation statements)

References 102 publications

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“…TMEM16F (also known as ANO6) mediated microglia polarization is involved in progression of AD and its inhibition shows neuroprotective effects in AD models 115 . ICAM-1 improves cognitive behaviors in 5xFAD mice by inhibiting NF-κB signaling 116 while PLSCR4 is a transcriptome biomarker hub gene in 5xFAD mice 117 . Overall, these AD/G9a-corregulated proteins were involved in mental/CNS/neurodevelopmental disorders, memory impairment, mental deterioration, and thrombosis/coagulation, among other diseases ( Figs.…”

Section: Resultsmentioning

confidence: 99%

Novel brain-penetrant inhibitor of G9a methylase blocks Alzheimer’s disease proteopathology for precision medication

Xie,

Sheehy,

Xiong

et al. 2023

Preprint

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Current amyloid beta-targeting approaches for Alzheimer disease (AD) therapeutics only slow cognitive decline for small numbers of patients. This limited efficacy exists because AD is a multifactorial disease whose pathological mechanism(s) and diagnostic biomarkers are largely unknown. Here we report a new mechanism of AD pathogenesis in which the histone methyltransferase G9a noncanonically regulates translation of a hippocampal proteome that defines the proteopathic nature of AD. Accordingly, we developed a novel brain-penetrant inhibitor of G9a, MS1262, across the blood-brain barrier to block this G9a-regulated, proteopathologic mechanism. Intermittent MS1262 treatment of multiple AD mouse models consistently restored both cognitive and noncognitive functions to healthy levels. Comparison of proteomic/phosphoproteomic analyses of MS1262-treated AD mice with human AD patient data identified multiple pathological brain pathways that elaborate amyloid beta and neurofibrillary tangles as well as blood coagulation, from which biomarkers of early stage of AD including SMOC1 were found to be affected by MS1262 treatment. Notably, these results indicated that MS1262 treatment may reduce or avoid the risk of blood clot burst for brain bleeding or a stroke. This mouse-to-human conservation of G9a-translated AD proteopathology suggests that the global, multifaceted effects of MS1262 in mice could extend to relieve all symptoms of AD patients with minimum side effect. In addition, our mechanistically derived biomarkers can be used for stage-specific AD diagnosis and companion diagnosis of individualized drug effects

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Section: Resultsmentioning

confidence: 99%

Novel brain-penetrant inhibitor of G9a methylase blocks Alzheimer’s disease proteopathology for precision medication

Xie,

Sheehy,

Xiong

et al. 2023

Preprint

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show abstract

“…Experimental evidence confirmed that biomarkers of endothelial dysfunction, such as intercellular adhesion molecule 1 (ICAM-1), are increased in AD; endothelial cells, astrocytes and microglia show enhanced levels of ICAM-1 in pathological states, and this plays a role in neuritic plaques on neurite growth and neurodegeneration [ 145 , 146 , 147 ]. Moreover, chemokines like CXCL2 work via the chemokine receptor (CXCR2) in neuronal cells, where they are involved in the pathophysiology of AD [ 148 ].…”

Section: Beneficial Effects Of Spirulina In Neurodegenerative Diseasesmentioning

confidence: 99%

Beneficial Effects of Spirulina Consumption on Brain Health

et al. 2022

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Spirulina is a microscopic, filamentous cyanobacterium that grows in alkaline water bodies. It is extensively utilized as a nutraceutical food supplement all over the world due to its high levels of functional compounds, such as phycocyanins, phenols and polysaccharides, with anti-inflammatory, antioxidant, immunomodulating properties both in vivo and in vitro. Several scientific publications have suggested its positive effects in various pathologies such as cardiovascular diseases, hypercholesterolemia, hyperglycemia, obesity, hypertension, tumors and inflammatory diseases. Lately, different studies have demonstrated the neuroprotective role of Spirulina on the development of the neural system, senility and a number of pathological conditions, including neurological and neurodegenerative diseases. This review focuses on the role of Spirulina in the brain, highlighting how it exerts its beneficial anti-inflammatory and antioxidant effects, acting on glial cell activation, and in the prevention and/or progression of neurodegenerative diseases, in particular Parkinson’s disease, Alzheimer’s disease and Multiple Sclerosis; due to these properties, Spirulina could be considered a potential natural drug.

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“…Intriguingly, each HRCK as signal target may initiate diverse biological process regulation of implicated endogenous cell types in neural microenvironment. For instance, Fractalkine (namely chemokine (C-X3-C motif) ligand 1, CX3CL1) was identified as a signal inducing microglia-mediated synapse elimination to regulate synaptic connectivity [ 44 ] and mitigating inflammation [ 45 ]; Intercellular adhesion molecule-1 (ICAM-1) was reported could protect neurons against Amyloid-β and improve cognitive behaviors in mice by inhibiting NF-κB [ 46 ]; Monocyte chemoattractant protein-1 alpha (MCP-1α, namely chemokine (C–C motif) ligand 2, CCL2) has been identified involved in the autophagy and apoptosis signaling pathway axis after spinal cord injury [ 47 ]; Notch1 signaling pathway has been reported could promote angiogenesis of cerebral microvasculature to protect ischemia reperfusion injury [ 48 ]; Soluble tumor necrosis factor-alpha (TNF-α) selectively inhibition was reported could change the neuroinflammatory response after moderate spinal cord injury in mice [ 49 ]; Interleukin-1 alpha (IL-1α) preconditioned mesenchymal stem cells exhibited promotive neuroprotection properties for ischemic stroke mice [ 50 ]; while IL-1β was reported as inhibitory target in inflammsome axis-mediated neutrophil infiltration could protect neurons in neurodegenerative disease [ 51 ]; PDGF-AA has been reported could improve the function recovery of spinal cord injury via subcutaneous administration [ 52 ]; and VEGF-A has been reviewed as the leading promoter of angiogenesis in health and disease, thus became the therapeutic targeting [ 53 ]. Therefore, the possible modulation effect of HRCK on neuronal and non-neuronal cells in neural injury position was especially concerned in our multiple cluster analyses.…”

Section: Discussionmentioning

confidence: 99%

Promotive effect of skin precursor-derived Schwann cells on brachial plexus neurotomy and motor neuron damage repair through milieu-regulating secretome

Chen,

Yang,

Cong

et al. 2024

Regenerative Therapy

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ICAM-1 protects neurons against Amyloid-β and improves cognitive behaviors in 5xFAD mice by inhibiting NF-κB

Cited by 16 publications

References 102 publications

Novel brain-penetrant inhibitor of G9a methylase blocks Alzheimer’s disease proteopathology for precision medication

Novel brain-penetrant inhibitor of G9a methylase blocks Alzheimer’s disease proteopathology for precision medication

Beneficial Effects of Spirulina Consumption on Brain Health

Promotive effect of skin precursor-derived Schwann cells on brachial plexus neurotomy and motor neuron damage repair through milieu-regulating secretome

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