Lactic acid promotes nucleus pulposus cell senescence and corresponding intervertebral disc degeneration via interacting with Akt

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Jan. 12, 2024

Language: Английский

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Dysfunctional Glucose Metabolism in Alzheimer’s Disease Onset and Potential Pharmacological Interventions

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 9540 - 9540

Published: Aug. 23, 2022

Alzheimer’s disease (AD) is the most common age-related dementia. The alteration in metabolic characteristics determines prognosis. Patients at risk show reduced glucose uptake brain. Additionally, type 2 diabetes mellitus increases of AD with increasing age. Therefore, changes cerebral cortex may predict histopathological diagnosis AD. shifts and metabolism, insulin resistance, oxidative stress, abnormal autophagy advance pathogenesis syndrome. Here, we summarize role altered metabolism for discuss potential pharmacological interventions defects to encourage development novel therapeutic methods.

Language: Английский

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Neurons and glial cells acquire a senescent signature after repeated mild traumatic brain injury in a sex-dependent manner

Frontiers in Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: Nov. 3, 2022

Mild traumatic brain injury (mTBI) is an important public health issue, as it can lead to long-term neurological symptoms and risk of neurodegenerative disease. The pathophysiological mechanisms driving this remain unclear, currently there are no effective therapies for mTBI. In study on repeated mTBI (rmTBI), we have induced three mild closed-skull injuries or sham procedures, separated by 24 h, in C57BL/6 mice. We show that rmTBI mice prolonged righting reflexes astrogliosis, with impairment the Morris water maze (MWM) light dark test. Cortical hippocampal tissue analysis revealed DNA damage form double-strand breaks, oxidative damage, R-loops, markers cellular senescence including p16 p21, signaling mediated cGAS-STING pathway. This identified novel sex differences after Although these were all increased both sexes, females had higher levels lower protein p16, proteins compared their male counterparts. Single-cell RNA sequencing mouse activation response, evidence senescence, pro-inflammatory reminiscent senescence-associated secretory phenotype (SASP) neurons glial cells. Cell-type specific changes also present immune activation, neurotransmission alterations excitatory inhibitory neurons, vascular dysfunction. Treatment injured senolytic drug ABT263 significantly reduced only males, but was not therapeutic females. reduction accompanied improved performance MWM. provides compelling contributes dysfunction rmTBI, may do so a sex-dependent manner.

Language: Английский

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Brain metabolism in Alzheimer’s disease: biological mechanisms of exercise

Translational Neurodegeneration, Journal Year: 2023, Volume and Issue: 12(1)

Published: June 26, 2023

Alzheimer's disease (AD) is a major subtype of neurodegenerative dementia caused by long-term interactions and accumulation multiple adverse factors, accompanied dysregulation numerous intracellular signaling molecular pathways in the brain. At cellular levels, neuronal milieu AD brain exhibits metabolic abnormalities, compromised bioenergetics, impaired lipid metabolism, reduced overall capacity, which lead to abnormal neural network activity neuroplasticity, thus accelerating formation extracellular senile plaques neurofibrillary tangles. The current absence effective pharmacological therapies for points urgent need investigate benefits non-pharmacological approaches such as physical exercise. Despite evidence that regular can improve dysfunction state, inhibit different pathophysiological associated with AD, influence pathological process exert protective effect, there no clear consensus on specific biological mechanisms underlying advantages Here, we review how exercise improves crucial processes disorders including glucose Aβ metabolism transport, iron tau pathology. How states health also presented. A better knowledge neurophysiological contribute development novel drugs improvement interventions.

Language: Английский

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Integrative metabolomics science in Alzheimer’s disease: Relevance and future perspectives

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 89, P. 101987 - 101987

Published: June 19, 2023

Language: Английский

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The mechanisms and functions of TNF-α in intervertebral disc degeneration

Experimental Gerontology, Journal Year: 2023, Volume and Issue: 174, P. 112119 - 112119

Published: Feb. 9, 2023

Low back pain (LBP) is one of the most common health problems in people's lives, which brings a massive burden to clinicians, and leading cause LBP intervertebral disc degeneration (IDD). IDD mainly caused by factors such as aging, mechanical stress, lack nutrition. The pathological mechanism very complex, involving inflammatory response, cell metabolism disorder, so on. Unfortunately, current treatment IDD, only relieving symptoms primary means patient's cannot effectively inhibit or reverse progression IDD. Tumor necrosis factor-α (TNF-α) multifunctional pro-inflammatory factor involved many diseases' processes. With in-depth study more evidence has shown that TNF-α an essential activator related metabolic responses, apoptosis, other processes extracellular dissociation disc. Therefore, anti-TNF-α therapy effective therapeutic target for alleviating especially inhibiting matrix degradation reducing responses. This article reviews role latest research progress inhibitors treating

Language: Английский

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Could Alzheimer’s disease be a maladaptation of an evolutionary survival pathway mediated by intracerebral fructose and uric acid metabolism?

American Journal of Clinical Nutrition, Journal Year: 2023, Volume and Issue: 117(3), P. 455 - 466

Published: Jan. 11, 2023

Language: Английский

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Relevance of Sugar Transport across the Cell Membrane

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6085 - 6085

Published: March 23, 2023

Sugar transport through the plasma membrane is one of most critical events in cellular nutrients; for example, glucose has a central role metabolism and homeostasis. The way sugars enter cell involves complex systems. Diverse protein systems participate traffic from extracellular side to cytoplasmic side. This diversity makes phenomenon highly regulated modulated satisfy different needs each line. beautiful thing about this process how evolutionary processes have diversified single function: move into cell. deregulation these entrance causes some diseases. Hence, it necessary study them search correct alterations utilize mechanisms promote health. review will highlight various importing valuable needed create homeostasis survival all kinds cells.

Language: Английский

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Mitochondrial-related microRNAs and their roles in cellular senescence

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 5, 2024

Aging is a natural aspect of mammalian life. Although cellular mortality inevitable, various diseases can hasten the aging process, resulting in abnormal or premature senescence. As cells age, they experience distinctive morphological and biochemical shifts, compromising their functions. Research has illuminated that senescence coincides with significant alterations microRNA (miRNA) expression profile. Notably, subset aging-associated miRNAs, originally encoded by nuclear DNA, relocate to mitochondria, manifesting mitochondria-specific presence. Additionally, mitochondria themselves house miRNAs mitochondrial DNA (mtDNA). These mitochondria-residing collectively referred as (mitomiRs), have been shown influence mtDNA transcription protein synthesis, thereby impacting functionality behavior. Recent studies suggest mitomiRs serve critical sensors for senescence, exerting control over homeostasis influencing metabolic reprogramming, redox equilibrium, apoptosis, mitophagy, calcium homeostasis-all processes intimately connected This review synthesizes current findings on mitomiRs, targets, functions, while also exploring involvement aging. Our goal shed light potential molecular mechanisms which contribute process.

Language: Английский

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Decoding the role of gut microbiota in Alzheimer’s pathogenesis and envisioning future therapeutic avenues

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Sept. 18, 2023

Alzheimer’s disease (AD) emerges as a perturbing neurodegenerative malady, with profound comprehension of its underlying pathogenic mechanisms continuing to evade our intellectual grasp. Within the intricate tapestry human health and affliction, enteric microbial consortium, ensconced within milieu gastrointestinal tract, assumes role cardinal significance. Recent epochs have borne witness investigations that posit marked divergences in composition gut microbiota between individuals grappling AD those favored by robust health. The composite vicissitudes configuration assembly are posited choreograph participatory inception progression AD, facilitated conduit acknowledged gut-brain axis. Notwithstanding, precise nature this interlaced relationship remains enshrouded recesses obscurity, poised for an exhaustive revelation. This review embarks upon endeavor focalize meticulously mechanistic sway exerted plunging profoundly into execution interventions govern microorganisms. In doing so, it bestows relevance therapeutic stratagems form bedrock AD’s management, all whilst casting prospective gaze horizon medical advancements.

Language: Английский

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