Geroscience and pathology: a new frontier in understanding age-related diseases

Pathology & Oncology Research, Journal Year: 2024, Volume and Issue: 30

Published: Feb. 23, 2024

Geroscience, a burgeoning discipline at the intersection of aging and disease, aims to unravel intricate relationship between process pathogenesis age-related diseases. This paper explores pivotal role played by geroscience in reshaping our understanding pathology, with particular focus on These diseases, spanning cardiovascular cerebrovascular disorders, malignancies, neurodegenerative conditions, significantly contribute morbidity mortality older individuals. We delve into fundamental cellular molecular mechanisms underpinning aging, including mitochondrial dysfunction senescence, elucidate their profound implications for various Emphasis is placed importance assessing key biomarkers biological age within realm pathology. also scrutinize interplay senescence cancer biology as central area focus, underscoring its paramount significance contemporary pathological research. Moreover, we shed light integration anti-aging interventions that target processes, such senolytics, mitochondria-targeted treatments, influence epigenetic regulation domain pathology In conclusion, concepts research heralds transformative paradigm shift disease promises breakthroughs prevention treatment.

Language: Английский

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Mitochondria in Alzheimer’s Disease Pathogenesis

Life, Journal Year: 2024, Volume and Issue: 14(2), P. 196 - 196

Published: Jan. 30, 2024

Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder that primarily affects persons aged 65 years above. It causes dementia with memory loss deterioration in thinking language skills. AD characterized by specific pathology resulting from the accumulation brain of extracellular plaques amyloid-β intracellular tangles phosphorylated tau. The importance mitochondrial dysfunction pathogenesis, while previously underrecognized, now more appreciated. Mitochondria are an essential organelle involved cellular bioenergetics signaling pathways. Mitochondrial processes crucial for synaptic activity such as mitophagy, trafficking, fission, fusion dysregulated brain. Excess fission fragmentation yield mitochondria low energy production. Reduced glucose metabolism also observed hypometabolic state, particularly temporo-parietal regions. This review addresses multiple ways which abnormal structure function contribute to AD. Disruption electron transport chain ATP production neurotoxic because cells have disproportionately high demands. In addition, oxidative stress, extremely damaging nerve cells, rises dramatically dyshomeostasis. Restoring health may be viable approach treatment.

Language: Английский

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Mitochondrial disorders leading to Alzheimer’s disease—perspectives of diagnosis and treatment

GeroScience, Journal Year: 2024, Volume and Issue: 46(3), P. 2977 - 2988

Published: March 8, 2024

Abstract Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common cause of dementia globally. The pathogenesis AD remains still unclear. three main features are extracellular deposits amyloid beta (Aβ) plaque, accumulation abnormal formation hyper-phosphorylated tau protein, neuronal loss. Mitochondrial impairment plays an important role in AD. There problems with decreased activity multiple complexes, disturbed mitochondrial fusion, fission or reactive oxygen species (ROS). Moreover, transport impaired Mouse models many research show disruptions anterograde retrograde transport. Both transportation network have huge impact on synapse loss and, as result, cognitive impairment. One very serious also disruption insulin signaling which impairs Aβ removal. Discovering precise mechanisms leading to enables us find new treatment possibilities. Recent studies indicate positive influence metformin antioxidants such MitoQ, SS-31, SkQ, MitoApo, MitoTEMPO, MitoVitE functioning hence prevent decline. Impairments may be treated division inhibitor-1 ceramide. Graphical (Graphic content via Canva Pro)

Language: Английский

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Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

Biomolecules, Journal Year: 2022, Volume and Issue: 12(11), P. 1676 - 1676

Published: Nov. 11, 2022

Damage or loss of brain cells and impaired neurochemistry, neurogenesis, synaptic nonsynaptic plasticity the lead to dementia in neurodegenerative diseases, such as Alzheimer's disease (AD). Injury synapses neurons accumulation extracellular amyloid plaques intracellular neurofibrillary tangles are considered main morphological neuropathological features AD. Age, genetic epigenetic factors, environmental stressors, lifestyle contribute risk AD onset progression. These factors associated with structural functional changes brain, leading cognitive decline. Biomarkers reflect cause specific function, especially pathways neurotransmission, neuroinflammation, bioenergetics, apoptosis, oxidative nitrosative stress. Even initial stages, is Aβ neurotoxicity, mitochondrial dysfunction, tau neurotoxicity. The integrative amyloid-tau-mitochondrial hypothesis assumes that primary neurotoxicity oligomers oligomers, their mutual synergy. For development new efficient drugs, targeting elimination potentiation effects, unwanted protein interactions biomarkers (mainly dysfunction) early stage seems promising.

Language: Английский

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Mitochondrial Transportation, Transplantation, and Subsequent Immune Response in Alzheimer’s Disease: An Update

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(9), P. 7151 - 7167

Published: Feb. 17, 2024

Language: Английский

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Therapeutic Potential of Targeting Mitochondria for Alzheimer’s Disease Treatment

Journal of Clinical Medicine, Journal Year: 2022, Volume and Issue: 11(22), P. 6742 - 6742

Published: Nov. 14, 2022

Alzheimer's disease (AD), a chronic and progressive neurodegenerative disease, is characterized by memory cognitive impairment the accumulation in brain of abnormal proteins, more precisely beta-amyloid (β-amyloid or Aβ) Tau proteins. Studies aimed at researching pharmacological treatments against AD have focused on molecules capable, one way another, preventing/eliminating accumulations aforementioned Unfortunately, than 100 years after discovery there still no effective therapy modifying biology behind nipping bud. This state affairs has made neuroscientists suspicious, so much that for several idea gained ground not direct neuropathological consequence taking place downstream deposition two toxic but rather multifactorial including mitochondrial dysfunction as an early event pathogenesis AD, occurring even before clinical symptoms. reason why search agents capable normalizing functioning these subcellular organelles vital importance nerve cells certainly to be considered promising approach design neuroprotective drugs preserving this organelle arrest delay progression disease. Here, our intent provide updated overview alterations related disorder therapeutic strategies (both natural synthetic) targeting dysfunction.

Language: Английский

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Carbon dioxide and MAPK signalling: towards therapy for inflammation

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Oct. 10, 2023

Abstract Inflammation, although necessary to fight infections, becomes a threat when it exceeds the capability of immune system control it. In addition, inflammation is cause and/or symptom many different disorders, including metabolic, neurodegenerative, autoimmune and cardiovascular diseases. Comorbidities advanced age are typical predictors more severe cases seasonal viral infection, with COVID-19 clear example. The primary importance mitogen-activated protein kinases (MAPKs) in course evident mechanisms by which cells infected SARS-CoV-2; cytokine storm that profoundly worsens patient’s condition; pathogenesis diseases, such as diabetes, obesity, hypertension, contribute worsened prognosis; post-COVID-19 complications, brain fog thrombosis. An increasing number reports have revealed MAPKs regulated carbon dioxide (CO 2 ); hence, we reviewed literature identify associations between CO possible therapeutic benefits resulting from elevation levels. regulates key processes leading inflammation, effects (or bicarbonate, HCO 3 − ) been documented all abovementioned comorbidities complications play roles. overlapping MAPK signalling pathways contexts allergy, apoptosis cell survival, pulmonary oedema (alveolar fluid resorption), mechanical ventilation–induced responses lungs related mitochondria also discussed.

Language: Английский

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Comparison of Monoamine Oxidase-A, Aβ Plaques, Tau, and Translocator Protein Levels in Postmortem Human Alzheimer’s Disease Brain

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10808 - 10808

Published: June 28, 2023

Increased monoamine oxidase-A (MAO-A) activity in Alzheimer’s disease (AD) may be detrimental to the point of neurodegeneration. To assess MAO-A AD, we compared four biomarkers, Aβ plaques, tau, translocator protein (TSPO), and postmortem AD. Radiotracers were [18F]FAZIN3 for MAO-A, [18F]flotaza [125I]IBETA [124/125I]IPPI [18F]FEPPA TSPO imaging. Brain sections anterior cingulate (AC; gray matter GM) corpus callosum (CC; white WM) from cognitively normal control (CN, n = 6) AD (n subjects imaged using autoradiography immunostaining. Using competition with clorgyline (R)-deprenyl, binding was confirmed selective levels brain sections. Increases plaque, found brains brains. The ratio GM versus CN 2.80, suggesting a 180% increase activity. GM-to-WM ratios CN, >50% observed (AD/CN 1.58). Linear positive correlations [18F]flotaza, [125I]IBETA, [125I]IPPI measured suggested an increases plaques tau Our results support finding that is elevated cortex thus provide new biomarker this region.

Language: Английский

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Correction of mitochondrial dysfunction with trimethoxy-substituted monocarbonyl curcumin analogues in experimental Alzheimer’s disease

Pharmacy & Pharmacology, Journal Year: 2024, Volume and Issue: 11(6), P. 471 - 481

Published: Jan. 30, 2024

Alzheimer’s disease (AD) is a neurodegenerative that terminal form of dementia with an alarming spread rate. The treatment AD usually involves symptomatic therapy, but the research field for new medicines to correct focus on pathogenetic keys disease, i.e., mitochondrial dysfunction. aim work was evaluate effect trimethoxy-substituted monocarbonyl curcumin analogues changes in function hippocampus rats. Materials and methods. modeled female Wistar rats by injection β-amyloid aggregates 1-42 into CA1 part hippocampus. tested compounds AZBAX4 AZBAX6 at dose 20 mg/kg each, as well reference donepezil 50 mg/kg, were administered orally 30 days after surgery. After specified time had passed, cellular respiration, citrate synthase activity, cytochrome-c-oxidase, succinate dehydrogenase, adenosine triphosphate (ATP) concentrations evaluated fraction rat Results. During study, it shown use contributed increase intensity aerobic metabolism 83.9 ( p <0.05) 35.9% <0.05), respectively, while reducing activity anaerobic one 27.7 20.6% respectively. Against background administration, there also significant synthase, dehydrogenase level ATP hippocampal tissue 112.8 117.1% led reactions – 24.0% activity– 80.0% concentration 68.5% <0.05). analyzed substances, decrease apoptosis-inducing factor hydrogen peroxide worth noting. Conclusion. Based obtained data, can be assumed contributes functional mitochondria cells rats, surpassing donepezil. It perspective continue further study possible correction AD.

Language: Английский

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Decrypting the Possible Mechanistic Role of Fenofibrate in Alzheimer's Disease and Type 2 Diabetes: The Truth and Mystery

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(5)

Published: March 1, 2025

Alzheimer's disease (AD) is a neurodegenerative caused by the progressive deposition of extracellular amyloid beta (Aβ) and intracellular neurofibrillary tangles (NFTs). Of note, metabolic disorders such as insulin resistance (IR) type 2 diabetes (T2D) are associated with development brain IR neurodegeneration. In addition, AD neuropathology linked cognitive impairment accelerate peripheral progression T2D. Therefore, there bidirectional relationship between T2D AD. It has been demonstrated that induce dysregulation peroxisome proliferator-activated receptor alpha (PPAR-α) leading to central disturbances. Hence, dysregulated PPAR-α could be shared mechanism in both T2D, restoration signalling agonist fenofibrate (FN) may alleviate this review aims shed light on potential involvement AD, how FN effective management seems dual neuroprotective antidiabetic effects can mitigate T2D-related complications modulating various cellular processes inflammatory pathways. conclusion, possible candidate different pathways involved pathogenesis these conditions.

Language: Английский

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