Anti-Inflammatory Role of the Klotho Protein and Relevance to Aging DOI Open Access
Gérald J. Prud’homme, Qinghua Wang

Published: Aug. 5, 2024

The α-Klotho protein (hereafter Klotho) is an obligate coreceptor for fibroblast growth factor 23 (FGF23). It produced in the kidneys, brain and other sites. Klotho insufficiency causes hyperphosphatemia anomalies. Importantly, it associated with chronic pathologies (often age-related) that have inflammatory component. This includes atherosclerosis, diabetes Alzheimer’s disease. Its mode of action these diseases not well understood, but inhibits or regulates multiple major pathways. has a membrane form, soluble form (s-Klotho). Cytosolic postulated characterized. s-Klotho endocrine properties are incompletely elucidated. binds to FGF receptor 1c (FGFR1c) widely expressed (including endothelial cells). also attaches FGF23, FGF23/Klotho FGFRs. Thus, might be roaming FGF23 coreceptor, functions. Notably, (cell-bound soluble) counteracts inflammation, appears mitigate related aging (inflammaging). NF-κB NLRP3 inflammasome. inflammasome requires priming by NF-κB, produces active IL-1β, pores cell death (pyroptosis). In accord, countered inflammation injury induced toxins, damage-associated molecular patterns (DAMPs), cytokines, reactive oxygen species (ROS). blocks TGF-β Wnt ligands, which lessens fibrotic Low loss muscle mass (sarcopenia), as occurs diseases. counters inhibitory effects myostatin on muscle, reduces improves repair following injury. Inhibition factors may protective diabetic retinopathy age-related macular degeneration (AMD). review examines functions especially potential applications.

Language: Английский

Gasdermin and MLKL necrotic cell death effectors: Signaling and diseases DOI Creative Commons
Kate E. Lawlor, James M. Murphy, James E. Vince

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(3), P. 429 - 445

Published: March 1, 2024

Language: Английский

Citations

22
Regulated cell death and its role in Alzheimer’s disease and amyotrophic lateral sclerosis DOI
Dietmar Rudolf Thal, Klara Gawor, Sebastiaan Moonen

et al.

Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 147(1)

Published: April 7, 2024

Language: Английский

Citations

22
Brain-targeted drug delivery - nanovesicles directed to specific brain cells by brain-targeting ligands DOI Creative Commons
Ricardo Moreira, Clévio Nóbrega, Luís Pereira de Almeida

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 17, 2024

Abstract Neurodegenerative diseases are characterized by extensive loss of function or death brain cells, hampering the life quality patients. Brain-targeted drug delivery is challenging, with a low success rate this far. Therefore, application targeting ligands in vehicles, such as lipid-based and polymeric nanoparticles, holds promise to overcome blood-brain barrier (BBB) direct therapies brain, addition protect their cargo from degradation metabolization. In review, we discuss barriers different types brain-targeting currently use brain-targeted peptides, proteins, aptamers, small molecules, antibodies. Moreover, present detailed review used nanoparticles specific like neurons (C4-3 aptamer, neurotensin, Tet-1, RVG, IKRG peptides), astrocytes (Aquaporin-4, D4, Bradykinin B2 antibodies), oligodendrocytes (NG-2 antibody biotinylated DNA aptamer conjugated streptavidin core Myaptavin-3064), microglia (CD11b antibody), neural stem cells (QTRFLLH, VPTQSSG, NFL-TBS.40–63 endothelial BBB (transferrin insulin choline). Reports demonstrated enhanced improved transport cell type targeted conjugation these nanoparticles. Hence, strategy allows implementation high-precision medicine, reduced side effects unwanted therapy clearance body. Nevertheless, accumulation some peripheral organs has been reported indicating that there still factors be achieve higher levels targeting. This collection studies exploring for highlight advantages limitations approach precision therapies.

Language: Английский

Citations

22
Parkinson’s Disease Drug Therapies in the Clinical Trial Pipeline: 2024 Update DOI Creative Commons

Kevin McFarthing,

Sue Buff,

Gary Rafaloff

et al.

Journal of Parkinson s Disease, Journal Year: 2024, Volume and Issue: 14(5), P. 899 - 912

Published: July 19, 2024

For the past five years, our annual reports have been tracking clinical development of new drug-based therapies for neurodegenerative condition Parkinson's disease (PD). These reviews followed progress both "symptomatic treatments" (ST - improves/reduces symptoms condition) and "disease-modifying (DMT attempts to delay/slow progression by addressing underlying biology PD). Efforts also made further categorize these experimental treatments based on their mechanisms action class drug.

Language: Английский

Citations

19
Parthanatos: Mechanisms, modulation, and therapeutic prospects in neurodegenerative disease and stroke DOI
Yang Liu,

Lauren Guttman,

Valina L. Dawson

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 228, P. 116174 - 116174

Published: March 27, 2024

Language: Английский

Citations

16
Dioscin Alleviates Periodontitis by Inhibiting NLRP3 Inflammasome Activation via Regulation of K+ Homeostasis and Mitochondrial Function DOI Creative Commons

Xue Jiang,

Xinxin Ding,

Jianxu Wei

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(4), P. 1375 - 1388

Published: Jan. 1, 2024

Gingival inflammation and alveolar bone loss are characteristic manifestations of periodontitis. Interleukin (IL)-1β, the maturation which is mainly regulated by NOD-like receptor protein (NLRP) 3 inflammasome, not only amplifies inflammatory response but also triggers osteoclastogenesis, thereby accelerating progression Dioscin, a natural steroid saponin, has been shown to inhibit NLRP3 inflammasome. Nevertheless, research on effectiveness Dioscin for management periodontitis remains scarce. In this study, was found dramatically reduce integral components ultimately limiting IL-1β secretion. Notably, inhibitory impact inflammasome might be exerted curbing generation mitochondrial (mt) reactive oxygen species (ROS) oxidized (ox) mtDNA, were mediated inhibition K

Language: Английский

Citations

10
Anti-Inflammatory Role of the Klotho Protein and Relevance to Aging DOI Creative Commons
Gérald J. Prud’homme, Qinghua Wang

Cells, Journal Year: 2024, Volume and Issue: 13(17), P. 1413 - 1413

Published: Aug. 24, 2024

The α-Klotho protein (hereafter Klotho) is an obligate coreceptor for fibroblast growth factor 23 (FGF23). It produced in the kidneys, brain and other sites. Klotho insufficiency causes hyperphosphatemia anomalies. Importantly, it associated with chronic pathologies (often age-related) that have inflammatory component. This includes atherosclerosis, diabetes Alzheimer's disease. Its mode of action these diseases not well understood, but inhibits or regulates multiple major pathways. has a membrane form soluble (s-Klotho). Cytosolic postulated characterized. s-Klotho endocrine properties are incompletely elucidated. binds to FGF receptor 1c (FGFR1c) widely expressed (including endothelial cells). also attaches FGF23, FGF23/Klotho FGFRs. Thus, might be roaming FGF23 coreceptor, functions. Notably, (cell-bound soluble) counteracts inflammation appears mitigate related aging (inflammaging). NF-κB NLRP3 inflammasome. inflammasome requires priming by produces active IL-1β, pores cell death (pyroptosis). In accord, countered injury induced toxins, damage-associated molecular patterns (DAMPs), cytokines, reactive oxygen species (ROS). blocks TGF-β Wnt ligands, which lessens fibrotic Low loss muscle mass (sarcopenia), as occurs diseases. counters inhibitory effects myostatin on muscle, reduces inflammation, improves repair following injury. inhibition factors may protective diabetic retinopathy age-related macular degeneration (AMD). review examines functions especially potential applications.

Language: Английский

Citations

10
Navigating the Complexities of Neuronal Signaling and Targets in Neurological Disorders: From Pathology to Therapeutics DOI

Divya Choudhary,

Muhammad Imran Khan, Zuber Khan

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177417 - 177417

Published: Feb. 1, 2025

Language: Английский

Citations

1
The complement system in neurodegenerative and inflammatory diseases of the central nervous system DOI Creative Commons

Luciana Negro-Demontel,

Adam F. Maleki,

Daniel S. Reich

et al.

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

Published: July 3, 2024

Neurodegenerative and neuroinflammatory diseases, including Alzheimer’s disease, Parkinson’s multiple sclerosis, affect millions of people globally. As aging is a major risk factor for neurodegenerative the continuous increase in elderly population across Western societies also associated with rising prevalence these debilitating conditions. The complement system, crucial component innate immune response, has gained increasing attention its multifaceted involvement normal development central nervous system (CNS) brain but as pathogenic driver several disease states. Although generally understood liver-derived blood or interstitial fluid operative protecting against bloodborne pathogens threats, recent research, particularly on role healthy diseased CNS, demonstrated importance locally produced activated components. Here, we provide succinct overview over known beneficial pathological roles CNS focus local sources complement, discussion potential recently discovered intracellularly active biology infection-triggered neurodegeneration.

Language: Английский

Citations

8
Gut microbiota-brain bile acid axis orchestrates aging-related neuroinflammation and behavior impairment in mice DOI Creative Commons
Junli Ma, Mingxiao Li, Yiyang Bao

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 208, P. 107361 - 107361

Published: Aug. 17, 2024

Emerging evidence shows that disrupted gut microbiota-bile acid (BA) axis is critically involved in the development of neurodegenerative diseases. However, alterations spatial distribution BAs among different brain regions command important functions during aging and their exact roles aging-related diseases are poorly understood. Here, we analyzed BA profiles cerebral cortex, hippocampus, hypothalamus young natural mice both sexes. The results showed altered sex- region- dependently, which TβMCA was consistently elevated sexes, particularly hippocampus hypothalamus. Furthermore, found accumulated-TβMCA stimulated microglia inflammation vitro shortened lifespan C. elegans, as well behavioral impairment neuroinflammation mice. In addition, metagenomic analysis suggested accumulation partially attributed to reduction BSH-carrying bacteria. Finally, rejuvenation microbiota by co-housing aged with restored homeostasis improved neurological dysfunctions conclusion, our current study highlighted potential improving neuro-impairment targeting microbiota-brain axis.

Language: Английский

Citations

8