Free Radical Biology and Medicine, Год журнала: 2025, Номер unknown
Опубликована: Апрель 1, 2025
Язык: Английский
Inflammopharmacology, Год журнала: 2025, Номер unknown
Опубликована: Янв. 3, 2025
Abstract The currently approved drugs for Alzheimer’s disease (AD) are only symptomatic treatment in the early stages of but they could not halt neurodegeneration, additionally, safety profile recently developed immunotherapy is a big issue. This review aims to explain importance repurposing technique and strategy develop therapy AD. We illustrated biological alterations pathophysiology AD including amyloid pathology, Tau oxidative stress, mitochondrial dysfunction, neuroinflammation, glutamate-mediated excitotoxicity, insulin signaling impairment, wingless-related integration site/ β -catenin signaling, autophagy. Additionally, we demonstrated different repurposed experimental models anti-inflammatory, anti-hypertensive, anti-diabetic, antiepileptic, antidepressant anticancer drugs. Further, showed pipeline FDA have promising therapeutic activity against AD, confirming value elucidate curative Graphical abstract
Язык: Английский
Процитировано
1
The FASEB Journal, Год журнала: 2025, Номер 39(2)
Опубликована: Янв. 21, 2025
Abstract Sarcopenia is an age‐related muscle atrophy syndrome characterized by the loss of strength and mass. Although many agents have been used to treat sarcopenia, there are no successful treatments date. In this study, we identified Danshensu sodium salt (DSS) as a substantial suppressive agent atrophy. We D‐galactose (DG)‐induced aging‐acceleration model, both in vivo vitro, confirm effect DSS on sarcopenia. inhibits expression atrophy‐related factors (MuRF1, MAFbx, myostatin, FoxO3a) DG‐induced mouse C2C12 human skeletal cells. Additionally, restored diameter reduced myotubes. Next, demonstrated that stimulates AMPK PGC1α through CaMKII. translocation FoxO3a into nucleus, thus inhibiting calcium‐dependent manner. initiated protein–protein interaction between PGC1α. The reduction PGC1α‐FoxO3a DG was DSS. Also, suppressed increased intracellular reactive oxygen species (ROS) DG. animal models, administration improved mass physical performance (grip hanging test) under accelerated aging conditions. These findings attenuates factors. Therefore, may be potential therapeutic for treatment
Язык: Английский
Процитировано
1
Archives of Pharmacal Research, Год журнала: 2022, Номер 45(7), С. 475 - 493
Опубликована: Июнь 29, 2022
Diabetic peripheral neuropathy (DPN) represents a severe microvascular condition that dramatically affects diabetic patients despite adequate glycemic control, resulting in high morbidity. Thus, recently, anti-diabetic drugs possess glucose-independent mechanisms attracted attention. This work aims to explore the potentiality of selective sodium-glucose cotransporter-2 inhibitor, empagliflozin (EMPA), ameliorate streptozotocin-induced DPN rats with insight into its precise signaling mechanism. Rats were allocated four groups, where control animals received vehicle daily for 2 weeks. In remaining was elicited by single intraperitoneal injections freshly prepared streptozotocin and nicotinamide (52.5 50 mg/kg, respectively). Then EMPA (3 mg/kg/p.o.) given two groups either alone or accompanied AMPK inhibitor dorsomorphin (0.2 mg/kg/i.p.). Despite non-significant anti-hyperglycemic effect, improved sciatic nerve histopathological alterations, scoring, myelination, fibers' count, conduction velocity. Moreover, alleviated responses different nociceptive stimuli along motor coordination. modulated ATP/AMP ratio, upregulated p-AMPK while reducing p-p38 MAPK expression, p-ERK1/2 consequently p-NF-κB p65 as well downstream mediators (TNF-α IL-1β), besides enhancing SOD activity lowering MDA content. downregulated mTOR stimulated ULK1 beclin-1. Likewise, reduced miR-21 enhanced RECK, MMP-2 -9 contents. EMPA's beneficial effects almost abolished administration. conclusion, displayed protective effect against independently from probably via modulating pathway modulate oxidative inflammatory burden, extracellular matrix remodeling, autophagy.
Язык: Английский
Процитировано
28
Physiology & Behavior, Год журнала: 2023, Номер 263, С. 114134 - 114134
Опубликована: Фев. 20, 2023
Язык: Английский
Процитировано
13
Psychopharmacology, Год журнала: 2024, Номер 241(12), С. 2565 - 2584
Опубликована: Авг. 19, 2024
Abstract Rationale Major depression has been an area of extensive research during the last decades, for it represents a leading cause disability and suicide. The stark rise rates influenced by life stressors, economic threats, pandemic era, resistance to classical treatments, made disorder rather challenging. Adult hippocampal neurogenesis plasticity are particularly sensitive dynamic interplay between autophagy inflammation. In fact, intricate balance two processes contributes neuronal homeostasis survival. Objectives Having demonstrated promising potentials in AMPK activation, major metabolic sensor regulator, empagliflozin (Empa) was investigated possible antidepressant properties reserpine rat model depression. Results While protocol elicited behavioral, biochemical, histopathological changes relevant depression, Empa outstandingly hindered these pathological perturbations. Importantly, autophagic response markedly declined with which disrupted AMPK/mTOR/Beclin1/LC3B machinery and, conversely, neuro-inflammation prevailed under influence NLRP3 inflammasome together oxidative/nitrative stress. Consequently, AMPK-mediated neurotrophins secretion obviously deteriorated through PKCζ/NF-κB/BDNF/CREB signal restriction. restored monoamines autophagy/inflammation balance, driven activation. By promoting atypical PKCζ phosphorylation (Thr403) subsequently phosphorylates NF-κB at Ser311, successfully reinforced BDNF/CREB neuroplasticity. latter finding supported CA3 toluidine blue staining reveal intact neurons. Conclusion current study highlights interesting role as regulator inflammatory responses pathology also pinpoints unusual contribution via AMPK/PKCζ/NF-κB/BDNF/CREB transduction. Accordingly, can have special benefits diabetic patients depressive symptoms. Limitations p -NF-κB (Ser311) on assembly activation not investigated, represent point further research. Graphical abstract
Язык: Английский
Процитировано
5
Life Sciences, Год журнала: 2022, Номер 310, С. 121002 - 121002
Опубликована: Сен. 30, 2022
Язык: Английский
Процитировано
17
Alzheimer s Research & Therapy, Год журнала: 2024, Номер 16(1)
Опубликована: Дек. 23, 2024
To evaluate the association between anti-diabetic agents and risks of dementia in patients with type 2 diabetes (T2D). Literature retrieval was conducted PubMed, Embase, Cochrane Central Register Controlled Trials Clinicaltrial.gov January 1995 October 2024. Observational studies randomized controlled trials (RCTs) T2D, which intercompared or compared them placebo, reported incidence were included. Conventional network meta-analyses these implemented. Results exhibited as odds ratio (OR) risk (RR) 95% confidence interval (CI). A total 41 observational (3,307,483 participants) 23 RCTs (155,443 In meta-analysis studies, non-users, sodium glucose cotransporter-2 inhibitor (SGLT-2i) (OR = 0.56, 95%CI, 0.45 to 0.69), glucagon-like peptide-1 receptor agonist (GLP-1RA) 0.58, 0.46 0.73), thiazolidinedione (TZD) 0.68, 0.57 0.81) metformin 0.89, 0.80 0.99) treatments all associated reduced T2D. The surface under cumulative ranking curve (SUCRA) evaluation conferred a rank order SGLT-2i > GLP-1RA TZD dipeptidyl peptidase-4 (DPP-4i) α-glucosidase (AGI) glucokinase activator (GKA) sulfonylureas glinides insulin terms cognitive benefits. Meanwhile, 0.43, 0.30 0.62), 0.54, 0.96) DPP-4i 0.73, 0.93) Alzheimer's disease while lower vascular observed receiving 0.42, 0.22 0.80) 0.52, 0.36 0.75) treatment. RCTs, comparable among placebo. Compared SGLT-2i, GLP-1RA, may serve optimal choice improve prognosis
Язык: Английский
Процитировано
4
Experimental Neurology, Год журнала: 2023, Номер 366, С. 114448 - 114448
Опубликована: Май 19, 2023
Язык: Английский
Процитировано
9
Journal of Alzheimer s Disease, Год журнала: 2024, Номер 101(2), С. 379 - 396
Опубликована: Авг. 27, 2024
Alzheimer's disease (AD) is one of the most common neurodegenerative disorders and characterized by a decrease in learning capacity, memory loss behavioral changes. In addition to well-recognized amyloid-β cascade hypothesis hyperphosphorylated Tau hypothesis, accumulating evidence has led proposal mitochondrial dysfunction as primary etiology AD. However, predominant molecular mechanisms underlying development progression AD have not been fully elucidated. Mitochondrial only considered an early event pathogenesis but also involved whole course disease, with numerous pathophysiological processes, including disordered energy metabolism, Ca2+ homeostasis hyperactive oxidative stress. current review, we integrated emerging summarize main alterations- bioenergetic inheritance, mitobiogenesis, fission- fusion dynamics, degradation, movement- pathogenesis; precisely identified regulators; discussed potential processes; highlighted leading players; noted additional incidental signaling pathway This review may help stimulate research exploring metabolically-oriented neuroprotection strategies therapies, better understanding link between pathogenesis.
Язык: Английский
Процитировано
3
International Immunopharmacology, Год журнала: 2025, Номер 148, С. 114110 - 114110
Опубликована: Янв. 24, 2025
Язык: Английский
Процитировано
0