Genetically Determined Levels of mTOR-Dependent Circulating Proteins and Risk of Multiple Sclerosis

Zhang, Yao-chen; Fan, Ke-Yi; Wang, Qi; Hu, Jing-Xi; Wang, Qian; Zhang, Heyi; Song, Shan; Zhao, Rong; Qiao, Jun; Zhang, Sheng‐Xiao

doi:10.1007/s40120-023-00455-y

Cited by 2 publications

(3 citation statements)

References 41 publications

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“…Interestingly, individuals with the neurodegenerative disorder multiple sclerosis (MS) also are significantly impacted by cognitive loss and dementia (Figure 1). Demyelinating disorders, such as MS, affect a significant proportion of the world's population [38,[126][127][128][129][130][131][132][133][134][135] (Table 1). MS is considered to be the most common demyelinating disorder that affects the immune system and the central nervous system through the function of myelin-producing cells [117,127,134,[136][137][138][139][140].…”

Section: Cognitive Loss and Dementia That Can Occur In Multiple Scler...mentioning

confidence: 99%

“…In experimental MS models, rapamycin with mTOR inhibition can prevent the clinical course of both relapsingremitting and chronic experimental autoimmune encephalomyelitis, suggesting important clinical applications for the treatment of MS [201]. Rapamycin, through the blockade of cytokine release and the inhibition of a microglia immune response, has been shown to reduce clinical symptomatology and inflammatory responses in models of experimental autoimmune encephalomyelitis [134]; it has been suggested that inhibition of mTOR pathways may be necessary to reduce the risk of MS development [135]. Autophagy activation during decreased mTOR activity can maintain mitochondrial function [444], prevent injury to dopamine-dependent cells [445], provide neuroprotection with glutamine-dependent mechanisms [446], and decrease ROS release [447].…”

Section: The Mechanistic Target Of Rapamycin and Multiple Sclerosismentioning

confidence: 99%

“…In regard to MS, mTOR can importantly impact inflammatory pathways that lead to neurodegeneration [3,73,85,211,244,285,461,462]. In clinical studies, mTOR pathway molecules may play an important role in determining the onset and progression of MS in patients [135]. Current therapies exist with metformin and biguanides that can impact neurodegenerative disease, and include demyelinating disease and cognitive loss [85,115,132,463].…”

Section: The Mechanistic Target Of Rapamycin and Multiple Sclerosismentioning

confidence: 99%

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Cognitive Impairment in Multiple Sclerosis

Maiese

2023

Bioengineering

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Almost three million individuals suffer from multiple sclerosis (MS) throughout the world, a demyelinating disease in the nervous system with increased prevalence over the last five decades, and is now being recognized as one significant etiology of cognitive loss and dementia. Presently, disease modifying therapies can limit the rate of relapse and potentially reduce brain volume loss in patients with MS, but unfortunately cannot prevent disease progression or the onset of cognitive disability. Innovative strategies are therefore required to address areas of inflammation, immune cell activation, and cell survival that involve novel pathways of programmed cell death, mammalian forkhead transcription factors (FoxOs), the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), and associated pathways with the apolipoprotein E (APOE-ε4) gene and severe acute respiratory syndrome coronavirus (SARS-CoV-2). These pathways are intertwined at multiple levels and can involve metabolic oversight with cellular metabolism dependent upon nicotinamide adenine dinucleotide (NAD+). Insight into the mechanisms of these pathways can provide new avenues of discovery for the therapeutic treatment of dementia and loss in cognition that occurs during MS.

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Section: Cognitive Loss and Dementia That Can Occur In Multiple Scler...mentioning

confidence: 99%

Section: The Mechanistic Target Of Rapamycin and Multiple Sclerosismentioning

confidence: 99%

Section: The Mechanistic Target Of Rapamycin and Multiple Sclerosismentioning

confidence: 99%

See 1 more Smart Citation

Cognitive Impairment in Multiple Sclerosis

Maiese

2023

Bioengineering

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The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk

Maiese

2023

Front. Immunol.

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Life expectancy is increasing throughout the world and coincides with a rise in non-communicable diseases (NCDs), especially for metabolic disease that includes diabetes mellitus (DM) and neurodegenerative disorders. The debilitating effects of metabolic disorders influence the entire body and significantly affect the nervous system impacting greater than one billion people with disability in the peripheral nervous system as well as with cognitive loss, now the seventh leading cause of death worldwide. Metabolic disorders, such as DM, and neurologic disease remain a significant challenge for the treatment and care of individuals since present therapies may limit symptoms but do not halt overall disease progression. These clinical challenges to address the interplay between metabolic and neurodegenerative disorders warrant innovative strategies that can focus upon the underlying mechanisms of aging-related disorders, oxidative stress, cell senescence, and cell death. Programmed cell death pathways that involve autophagy, apoptosis, ferroptosis, and pyroptosis can play a critical role in metabolic and neurodegenerative disorders and oversee processes that include insulin resistance, β-cell function, mitochondrial integrity, reactive oxygen species release, and inflammatory cell activation. The silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), AMP activated protein kinase (AMPK), and Wnt1 inducible signaling pathway protein 1 (WISP1) are novel targets that can oversee programmed cell death pathways tied to β-nicotinamide adenine dinucleotide (NAD+), nicotinamide, apolipoprotein E (APOE), severe acute respiratory syndrome (SARS-CoV-2) exposure with coronavirus disease 2019 (COVID-19), and trophic factors, such as erythropoietin (EPO). The pathways of programmed cell death, SIRT1, AMPK, and WISP1 offer exciting prospects for maintaining metabolic homeostasis and nervous system function that can be compromised during aging-related disorders and lead to cognitive impairment, but these pathways have dual roles in determining the ultimate fate of cells and organ systems that warrant thoughtful insight into complex autofeedback mechanisms.

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Genetically Determined Levels of mTOR-Dependent Circulating Proteins and Risk of Multiple Sclerosis

Cited by 2 publications

References 41 publications

Cognitive Impairment in Multiple Sclerosis

Cognitive Impairment in Multiple Sclerosis

The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk

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