Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 338, P. 119095 - 119095
Published: Nov. 12, 2024
Language: Английский
Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(10), P. 7930 - 7949
Published: March 5, 2024
Language: Английский
Citations
17
Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(4), P. 1069 - 1076
Published: May 17, 2024
The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease Parkinson’s disease. Obesity-related conditions like type 2 diabetes non-alcoholic fatty liver exacerbate this relationship. Peripheral lipid accumulation, particularly in liver, initiates a cascade inflammatory processes that extend brain, influencing critical regulatory regions. Ceramide palmitate, key components, along with transporters lipocalin-2 apolipoprotein E, contribute neuroinflammation by disrupting blood–brain barrier integrity promoting gliosis. insulin resistance further exacerbates brain neuroinflammation. Preclinical interventions targeting peripheral metabolism signaling pathways have shown promise reducing animal models. However, translating these findings clinical practice requires investigation into human subjects. In conclusion, dysfunction, inflammation, are integral neurodegeneration. Understanding complex mechanisms holds potential for identifying novel therapeutic targets improving outcomes diseases.
Language: Английский
Citations
10
Frontiers in Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 18
Published: Feb. 5, 2025
Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting millions of individuals worldwide. A hallmark PD pathology the accumulation α-synuclein (α-Syn), small protein known to support neuronal development and function. However, in PD, α-Syn cumulatively misfolds into toxic aggregates that disrupt cellular processes contribute damage neurodegeneration. Previous studies implicated AKT signaling pathway toxicity models suggesting as potential therapeutic target. Here, we investigated effect inhibition Drosophila model synucleinopathy. We observed administration inhibitor, A-443654 led mild improvements both survival motor function flies expressing human α-Syn. Genetic revealed reduction levels decreased levels, concomitant with improved physiological outcomes. The protective effects appear operate through fly ortholog NF-κB, Relish, link between NF-κB regulating levels. These findings highlight cascade target for synucleinopathies provide insights mechanisms could be utilized reduce related disorders, such multiple system atrophy.
Language: Английский
Citations
1
Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14
Published: Nov. 8, 2023
Life expectancy is increasing throughout the world and coincides with a rise in non-communicable diseases (NCDs), especially for metabolic disease that includes diabetes mellitus (DM) neurodegenerative disorders. The debilitating effects of disorders influence entire body significantly affect nervous system impacting greater than one billion people disability peripheral as well cognitive loss, now seventh leading cause death worldwide. Metabolic disorders, such DM, neurologic remain significant challenge treatment care individuals since present therapies may limit symptoms but do not halt overall progression. These clinical challenges to address interplay between warrant innovative strategies can focus upon underlying mechanisms aging-related oxidative stress, cell senescence, death. Programmed pathways involve autophagy, apoptosis, ferroptosis, pyroptosis play critical role oversee processes include insulin resistance, β-cell function, mitochondrial integrity, reactive oxygen species release, inflammatory activation. silent mating type information regulation 2 homolog 1
Language: Английский
Citations
20
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 117009 - 117009
Published: June 21, 2024
Cyclic adenosine monophosphate (cAMP) is a key second messenger that regulates signal transduction pathways pivotal for numerous biological functions. Intracellular cAMP levels are spatiotemporally regulated by their hydrolyzing enzymes called phosphodiesterases (PDEs). It has been shown increased in the central nervous system (CNS) promote neuroplasticity, neurotransmission, neuronal survival, and myelination while suppressing neuroinflammation. Thus, elevating through PDE inhibition provides therapeutic approach multiple CNS disorders, including sclerosis, stroke, spinal cord injury, amyotrophic lateral traumatic brain Alzheimer's disease. In particular, of cAMP-specific PDE4 subfamily widely studied because its high expression CNS. So far, clinical translation full inhibitors hampered dose-limiting side effects. Hence, focusing on signaling cascades downstream activated upon presents promising strategy, offering novel pharmacologically safe targets treating disorders. Yet, underlying PDE(4) remain partially elusive. This review comprehensive overview existing knowledge regarding mediators induced or stimulators. Furthermore, we highlight gaps future perspectives may incentivize additional research concerning inhibition, thereby providing approaches
Language: Английский
Citations
7
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7033 - 7033
Published: June 27, 2024
Overexpression of protein tyrosine phosphatase 1B (PTP1B) disrupts signaling pathways and results in numerous human diseases. In particular, its involvement has been well documented the pathogenesis metabolic disorders (diabetes mellitus type I II, fatty liver disease, obesity); neurodegenerative diseases (Alzheimer's Parkinson's disease); major depressive disorder; calcific aortic valve disease; as several cancer types. Given this multitude therapeutic applications, shortly after identification PTP1B role, pursuit to introduce safe selective enzyme inhibitors began. Regrettably, efforts undertaken so far have proved unsuccessful, since all proposed failed, or are yet complete, clinical trials. Intending aid introduction new generation inhibitors, work collects organizes current state art. review intends elucidate intricate relations between associated with overexpression PTP1B, we believe that it is utmost significance establish follow a brand-new holistic approach treatment interconnected conditions. With mind, comprehensive aims validate promising molecular target, reinforce future research direction.
Language: Английский
Citations
7
Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)
Published: June 10, 2024
Language: Английский
Citations
5
Cells, Journal Year: 2023, Volume and Issue: 12(22), P. 2595 - 2595
Published: Nov. 9, 2023
Metabolic disorders and diabetes (DM) impact more than five hundred million individuals throughout the world are insidious in onset, chronic nature, yield significant disability death. Current therapies that address nutritional status, weight management, pharmacological options may delay but cannot alter disease course or functional organ loss, such as dementia degeneration of systemic bodily functions. Underlying these challenges onset aging associated with increased lifespan, telomere dysfunction, oxidative stress generation lead to multi-system dysfunction. These hurdles point urgent need underlying mechanisms innovative applications. New treatment strategies involve non-coding RNA pathways microRNAs (miRNAs) circular ribonucleic acids (circRNAs), Wnt signaling, Wnt1 inducible signaling pathway protein 1 (WISP1) dependent upon programmed cell death pathways, cellular metabolic AMP-activated kinase (AMPK) nicotinamide, growth factor Non-coding RNAs, AMPK cornerstone for overseeing complex offer avenues DM will necessitate continued appreciation ability each independently unison influence clinical outcome.
Language: Английский
Citations
11
Neurochemical Research, Journal Year: 2024, Volume and Issue: 49(4), P. 1017 - 1033
Published: Jan. 7, 2024
Abstract Huntington’s disease (HD) is an autosomal-dominant neurodegenerative disorder characterized by motor, psychiatric and cognitive symptoms. Injection of 3-nitropropionic acid (3-NP) a widely used experimental model for induction HD. The current study aimed to inspect the potential neuroprotective properties azilsartan (Azil), angiotensin II type 1 receptor blocker (ATR1), in 3-NP-induced striatal neurotoxicity rats. Rats were randomly allocated into five groups treated 14 days as follows: group I received normal saline; Azil (10 mg/kg, p.o.); III 3-NP i.p); IV V (5 or 10 p.o, respectively) h prior injection. Both doses markedly attenuated motor behavioural dysfunction well histopathological alterations caused 3-NP. In addition, balanced neurotransmitters levels evidenced increase gamma-aminobutyric content decrease glutamate content. also amended neuroinflammation oxidative stress via modulating IĸB/NF-ĸB KEAP1/Nrf2 downstream signalling pathways, reducing iNOS COX2 levels. Moreover, demonstrated anti-apoptotic activity caspase-3 level BAX/BCL2 ratio. conclusion, present reveals behavioural, biochemical changes These findings might be attributed inhibition ATR1/NF-κB signalling, modulation Nrf2/KEAP1 anti-inflammatory, anti-oxidant properties. Graphical
Language: Английский
Citations
4
Life Sciences, Journal Year: 2025, Volume and Issue: 362, P. 123378 - 123378
Published: Jan. 7, 2025
Language: Английский
Citations
0