Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm

Maiese, Kenneth

doi:10.52586/4971

Cited by 23 publications

(18 citation statements)

References 264 publications

(421 reference statements)

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“…In large developing countries, such as China and India, the elderly population is expected to increase from five to ten percent in the coming years [9,10]. The observed increase in lifespan for individuals has several components that have resulted from measures focused on improving sanitation and reducing infection, allowing greater access to higher quality healthcare, the incorporation of early diagnostic and preventive measures, and quickly identifying individuals susceptible to both acute and chronic illnesses [5,[11][12][13][14][15][16][17][18][19][20][21][22].…”

Section: Increased Lifespan Aging Cellular Senescence and Nervous Sys...mentioning

confidence: 99%

“…Neurodegenerative disorders impact more than fifteen percent of the global population and comprise greater than six hundred disease entities that can result in severe disability and death [10,37,[41][42][43][44][45][46][47]. More than seven million individuals die each year from diseases of the nervous system [2,18]. A significant factor that plays a role in the onset and progression of neurodegenerative disorders is the cellular mechanisms of aging [21,40,[48][49][50][51][52][53][54].…”

Section: Increased Lifespan Aging Cellular Senescence and Nervous Sys...mentioning

confidence: 99%

“…Social services and medical needs in the year 2030 will require 2 trillion USD every year in the US alone, as currently greater than 4 million individuals require resources of 3.8 billion USD total every year for care. Although possibly underestimated, it is predicted that market needs for AD will exceed 11 billion USD [18,105,115]. Additional expenses also come under consideration, such as the need to employ close to 70 million social care individuals and health care staff for the essential need of companion and adult behavior care, as well as outreach systems to address social needs [27,28,116].…”

Section: Cognitive Impairment In Neurodegenerationmentioning

confidence: 99%

“…More than 10 million individuals suffer from PD in the world, which includes 50,000 new cases annually in the US, and many suffer from cognitive loss [117,123]. The number of individuals with PD is expected to double by the year 2030 [10,18,124,125]. More than $52 billion USD are spent in the US alone per year, with an annual cost per patient that approaches approximately $25,000 US dollars per year.…”

Section: Cognitive Impairment In Neurodegenerationmentioning

confidence: 99%

“…FoxOs are especially interesting since they can influence behavior and memory loss [18,203,309,316]. More than one hundred genes in the forkhead family and nine-teen human subgroups have been described.…”

Section: Mammalian Forkhead Transcription Factors 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: Increased Lifespan Aging Cellular Senescence and Nervous Sys...mentioning

confidence: 99%

Section: Increased Lifespan Aging Cellular Senescence and Nervous Sys...mentioning

confidence: 99%

Section: Cognitive Impairment In Neurodegenerationmentioning

confidence: 99%

Section: Cognitive Impairment In Neurodegenerationmentioning

confidence: 99%

Section: Mammalian Forkhead Transcription Factors and Multiple Sclerosismentioning

confidence: 99%

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Cognitive Impairment in Multiple Sclerosis

Maiese

2023

Bioengineering

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Circadian regulation of hippocampal function is disrupted with corticosteroid treatment

Birnie

Claydon

Troy

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Disrupted circadian activity is associated with many neuropsychiatric disorders. A major coordinator of circadian biological systems is adrenal glucocorticoid secretion which exhibits a pronounced preawakening peak that regulates metabolic, immune, and cardiovascular processes, as well as mood and cognitive function. Loss of this circadian rhythm during corticosteroid therapy is often associated with memory impairment. Surprisingly, the mechanisms that underlie this deficit are not understood. In this study, in rats, we report that circadian regulation of the hippocampal transcriptome integrates crucial functional networks that link corticosteroid-inducible gene regulation to synaptic plasticity processes via an intrahippocampal circadian transcriptional clock. Further, these circadian hippocampal functions were significantly impacted by corticosteroid treatment delivered in a 5-d oral dosing treatment protocol. Rhythmic expression of the hippocampal transcriptome, as well as the circadian regulation of synaptic plasticity, was misaligned with the natural light/dark circadian-entraining cues, resulting in memory impairment in hippocampal-dependent behavior. These findings provide mechanistic insights into how the transcriptional clock machinery within the hippocampus is influenced by corticosteroid exposure, leading to adverse effects on critical hippocampal functions, as well as identifying a molecular basis for memory deficits in patients treated with long-acting synthetic corticosteroids.

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Alterations in protein kinase networks in astrocytes and neurons derived from patients with familial Alzheimer’s Disease

Henkel

Joyce

Shedroff

et al. 2022

Preprint

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Neurons and astrocytes derived from Alzheimers Disease (AD) patient induced pluripotent stem cells are an evolving technology used to study the pathogenesis and etiology of AD. As the utility of mouse models of AD are increasingly coming into questions, using iPSC technology may offer an opportunity to study this disease with human substrates. Herein, we using a hypothesis generating platform, the PamGene12 Kinome Array, to identify core protein kinases in neurons and astrocytes derived from familial AD patient iPSCs. We identified five core protein kinases in these cells and examined the pathways in which they are enriched. Importantly, we complement our findings using an in-silico approach with postmortem AD brain datasets. While these protein kinases have been conceptualized in the context of traditional AD pathology, they have not been explored in the context of aberrant signaling in the pathophysiology of the disease.

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Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm

Cited by 23 publications

References 264 publications

Cognitive Impairment in Multiple Sclerosis

Cognitive Impairment in Multiple Sclerosis

Circadian regulation of hippocampal function is disrupted with corticosteroid treatment

Alterations in protein kinase networks in astrocytes and neurons derived from patients with familial Alzheimer’s Disease

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