Hallmarks of neurodegenerative diseases

Cell, Journal Year: 2023, Volume and Issue: 186(4), P. 693 - 714

Published: Feb. 1, 2023

Summary

Decades of research have identified genetic factors and biochemical pathways involved in neurodegenerative diseases (NDDs). We present evidence for the following eight hallmarks NDD: pathological protein aggregation, synaptic neuronal network dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA RNA defects, inflammation, cell death. describe hallmarks, their biomarkers, interactions as a framework to study NDDs using holistic approach. The can serve basis defining pathogenic mechanisms, categorizing different based on primary stratifying patients within specific NDD, designing multi-targeted, personalized therapies effectively halt NDDs.

Language: Английский

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Aging and age‐related diseases: from mechanisms to therapeutic strategies

Biogerontology, Journal Year: 2021, Volume and Issue: 22(2), P. 165 - 187

Published: Jan. 27, 2021

Language: Английский

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DNA Damage: From Threat to Treatment

Cells, Journal Year: 2020, Volume and Issue: 9(7), P. 1665 - 1665

Published: July 10, 2020

DNA is the source of genetic information, and preserving its integrity essential in order to sustain life. The genome continuously threatened by different types lesions, such as abasic sites, mismatches, interstrand crosslinks, or single-stranded double-stranded breaks. As a consequence, cells have evolved specialized damage response (DDR) mechanisms integrity. By orchestrating multilayer signaling cascades specific for type lesion that occurred, DDR ensures information preserved overtime. In last decades, repair been thoroughly investigated untangle these complex networks pathways processes. result, key factors identified control coordinate circuits time space. first part this review, we describe critical processes encompassing sensing resolution. second part, illustrate consequences partial complete failure machinery. Lastly, will report examples which knowledge has instrumental develop novel therapies based on editing technologies, CRISPR-Cas.

Language: Английский

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STING promotes senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the NF-κB signaling pathway

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(1)

Published: Jan. 4, 2021

Abstract Damaged deoxyribonucleic acid (DNA) is a primary pathologic factor for osteoarthritis (OA); however, the mechanism by which DNA damage drives OA unclear. Previous research demonstrated that cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) participates in response. As result, current study aimed at exploring role STING, major effector cGAS-STING signaling casacde, progress vitro, as well vivo. In this study, expression STING was evaluated human and mouse tissues, chondrocytes exposed to interleukin-1 beta (IL-1β). The influences on metabolism extracellular matrix (ECM), apoptosis, senescence, were assessed overexpressing knocking-down chondrocytes. Moreover, NF-κB-signaling casacde its regulatory effects ECM metabolism, senescence explored. knockdown lentivirus intra-articularly injected evaluate therapeutic impact mice results showed remarkably elevated tissues IL-1β. Overexpression promoted MMP13, ADAMTS5, but suppressed Aggrecan, Collagen II; it also enhanced apoptosis those untreated with mechanistic activated NF-κB cascade, whereas blockage attenuated STING-induced ameliorated imbalance. vivo alleviated destabilization medial meniscus-induced development mice. conclusion, promotes activating suppression may provide novel approach therapy.

Language: Английский

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Genome-wide RNA polymerase stalling shapes the transcriptome during aging

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(2), P. 268 - 279

Published: Jan. 19, 2023

Gene expression profiling has identified numerous processes altered in aging, but how these changes arise is largely unknown. Here we combined nascent RNA sequencing and polymerase II chromatin immunoprecipitation followed by to elucidate the underlying mechanisms triggering gene wild-type aged mice. We found that 2-year-old liver, 40% of elongating polymerases are stalled, lowering productive transcription skewing transcriptional output a gene-length-dependent fashion. demonstrate this stress caused endogenous DNA damage explains majority aging most mainly postmitotic organs, specifically affecting hallmark pathways such as nutrient sensing, autophagy, proteostasis, energy metabolism, immune function cellular resilience. Age-related evolutionary conserved from nematodes humans. Thus, accumulation stochastic during deteriorates basal transcription, which establishes age-related transcriptome causes dysfunction key pathways, disclosing functionally underlies major aspects normal aging.

Language: Английский

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Emerging Therapeutic Strategies to Overcome Drug Resistance in Cancer Cells

Cancers, Journal Year: 2024, Volume and Issue: 16(13), P. 2478 - 2478

Published: July 7, 2024

The rise of drug resistance in cancer cells presents a formidable challenge modern oncology, necessitating the exploration innovative therapeutic strategies. This review investigates latest advancements overcoming mechanisms employed by cells, focusing on emerging modalities. intricate molecular insights into resistance, including genetic mutations, efflux pumps, altered signaling pathways, and microenvironmental influences, are discussed. Furthermore, promising avenues offered targeted therapies, combination treatments, immunotherapies, precision medicine approaches highlighted. Specifically, synergistic effects combining traditional cytotoxic agents with molecularly inhibitors to circumvent pathways examined. Additionally, evolving landscape immunotherapeutic interventions, immune checkpoint adoptive cell is explored terms bolstering anti-tumor responses evasion mechanisms. Moreover, significance biomarker-driven strategies for predicting monitoring treatment underscored, thereby optimizing outcomes. For future direction paradigms, current focused prevailing challenges improving patient outcomes, through an integrative analysis these

Language: Английский

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The emerging role of oxidative stress in inflammatory bowel disease

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: July 15, 2024

Inflammatory bowel disease (IBD) is a chronic immune-mediated condition that affects the digestive system and includes Crohn’s (CD) ulcerative colitis (UC). Although exact etiology of IBD remains uncertain, dysfunctional immunoregulation gut believed to be main culprit. Amongst immunoregulatory factors, reactive oxygen species (ROS) nitrogen (RNS), components oxidative stress event, are produced at abnormally high levels in IBD. Their destructive effects may contribute disease’s initiation propagation, as they damage lining activate inflammatory signaling pathways, further exacerbating inflammation. Oxidative markers, such malondialdehyde (MDA), 8-hydroxy-2’-deoxyguanosine (8-OHdG), serum-free thiols (R-SH), can measured blood stool patients with These markers elevated IBD, their correlate severity disease. Thus, used not only diagnosis but also monitoring response treatment. It targeted treatment through use antioxidants, including vitamin C, E, glutathione, N-acetylcysteine. In this review, we summarize role pathophysiology its diagnostic targets, potential application antioxidant therapies manage treat

Language: Английский

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Impact of Vitamin D on Skin Aging, and Age-Related Dermatological Conditions

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 20, 2025

Human skin is a physical and biochemical barrier that protects the internal body from external environment. Throughout person’s life, undergoes both intrinsic extrinsic aging, leading to microscopic macroscopic changes in its morphology. In addition, repair processes slow with making older population more susceptible diseases. Intrinsic factors associated advanced age gradually degrade dermal collagen matrix, resulting fine wrinkles reduced elasticity; this accelerated post-menopausal women due estrogen deficiency. contrast, age, primarily caused by exposure ultraviolet (UV) radiation, lead coarse wrinkles, solar elastosis, hyperkeratosis, irregular pigmentation, cancers. UVB while contributing photo-aging, also induces cutaneous synthesis of vitamin D. Vitamin D, turn, oxidative stress, inflammation, DNA damage, thereby delaying chronological photo-aging. Moreover, research has demonstrated an association between lower D levels higher prevalence certain This review explores summarizes critical role aging age-related The data presented highlight importance maintaining adequacy throughout life.

Language: Английский

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DNA Damage Response and Immune Defense

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(20), P. 7504 - 7504

Published: Oct. 12, 2020

DNA damage is the cause of numerous human pathologies including cancer, premature aging, and chronic inflammatory conditions. The response (DDR), in turn, coordinates checkpoint activation promotes removal lesions. In recent years, several studies have shown how DDR immune system are tightly connected, revealing an important crosstalk between two them. This interesting interplay has opened up new perspectives clinical for immunological diseases as well cancer treatment. this review, we provide overview, from cellular to molecular pathways, on communicate share crucial commitment maintaining genomic fitness.

Language: Английский

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Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(19), P. 7264 - 7264

Published: Oct. 1, 2020

The protective ozone layer is continually depleting due to the release of deteriorating environmental pollutants. diminished contributes excessive exposure cells ultraviolet (UV) radiation. This leads various cellular responses utilized restore homeostasis exposed cells. DNA primary chromophore that absorbs sunlight energy. Exposure genomic UV light formation multitude types damage (depending on wavelength and time) are removed by effectively working repair pathways. aim this review summarize current knowledge considering response radiation with special focus give a comprehensive insight for new researchers in field. We also highlight most important future prospects application progressing clinical control diverse pathologies.

Language: Английский

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