Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Фев. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Язык: Английский

---

The expanding incretin universe: from basic biology to clinical translation

Diabetologia, Год журнала: 2023, Номер 66(10), С. 1765 - 1779

Опубликована: Март 28, 2023

Язык: Английский

---

Central glucagon-like peptide 1 receptor activation inhibits Toll-like receptor agonist-induced inflammation

Cell Metabolism, Год журнала: 2023, Номер 36(1), С. 130 - 143.e5

Опубликована: Дек. 18, 2023

Язык: Английский

---

GLP-1 Receptor Agonists: A New Treatment in Parkinson’s Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 3812 - 3812

Опубликована: Март 29, 2024

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Recent data highlight similarities between diseases, including PD and type 2 diabetes mellitus (T2DM), suggesting a crucial interplay gut–brain axis. Glucagon-like peptide-1 receptor (GLP-1R) agonists, known for their use in T2DM treatment, are currently extensively studied as novel modifying agents. For this narrative review article, we searched PubMed Scopus databases peer-reviewed research, articles clinical trials regarding GLP-1R agonists published English language with no time restrictions. We also screened references selected possible additional order to include key recent evidence. Many on animal models preclinical studies show that GLP1-R can restore dopamine levels, inhibit dopaminergic loss, attenuate neuronal degeneration alleviate motor non-motor features PD. Evidence from very promising, enhancing possibility adding current armamentarium drugs available treatment.

Язык: Английский

---

GLP-1 receptor agonists: A novel pharmacotherapy for binge eating (Binge eating disorder and bulimia nervosa)? A systematic review

Journal of Clinical & Translational Endocrinology, Год журнала: 2024, Номер 35, С. 100333 - 100333

Опубликована: Фев. 29, 2024

Systematically review evidence on using GLP-1RAs for reducing BEB in BED and BN. Comprehensive literature search (PubMed Google Scholar) conducted studies evaluating GLP-1Ras BEB. Extracted data study characteristics, efficacy, safety. Studies show that (liraglutide dulaglutide) reduce BE frequency comorbidities addition to favorable psychiatric side effect profile compared current options. However, large-scale, blinded placebo-controlled trials are lacking. Early findings suggest promising effects of rigorous clinical needed firmly establish dosing, safety, comparative effectiveness before considering a viable novel approach.

Язык: Английский

---

Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial

The Lancet, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

GLP-1 receptor agonists have neurotrophic properties in in-vitro and in-vivo models of Parkinson's disease results epidemiological studies small randomised trials suggested possible benefits for risk progression disease. We aimed to establish whether the agonist, exenatide, could slow rate did a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial at six research hospitals UK. Participants were aged 25-80 years with diagnosis disease, Hoehn Yahr stage 2·5 or less when on dopaminergic treatment, treatment least 4 weeks before enrolment. randomly assigned (1:1) using web-based system minimisation according study site receive extended-release exenatide 2 mg by subcutaneous pen injection once per week over 96 weeks, visually identical placebo. All participants all team members sites masked randomisation allocation. The primary outcome was Movement Disorder Society-sponsored revision Unified Disease Rating Scale (MDS-UPDRS) part III score, off medication analysed intention-to-treat population linear mixed modelling approach. This is registered ISRCTN (14552789), EudraCT (2018-003028-35), ClinicalTrials.gov (NCT04232969). Between Jan 23, 2020, April 2022, 215 screened eligibility, whom 194 (n=97) placebo (n=97). 56 (29%) female 138 (71%) male. 92 group had one follow-up visit included analyses. At MDS-UPDRS OFF-medication scores increased (worsened) mean 5·7 points (SD 11·2) group, 4·5 11·4) (adjusted coefficient effect 0·92 [95% CI -1·56 3·39]; p=0·47). Nine (9%) serious adverse event compared 11 (11%) group. Our findings suggest that safe well tolerated. found no evidence support as disease-modifying people Studies agents show better target engagement specific subgroups patients are needed there any use National Institute Health Care Research Cure Parkinson's.

Язык: Английский

---

Therapeutic targeting of obesity-induced neuroinflammation and neurodegeneration

Frontiers in Endocrinology, Год журнала: 2025, Номер 15

Опубликована: Янв. 17, 2025

Obesity is a major modifiable risk factor leading to neuroinflammation and neurodegeneration. Excessive fat storage in obesity promotes the progressive infiltration of immune cells into adipose tissue, resulting release pro-inflammatory factors such as cytokines adipokines. These inflammatory mediators circulate through bloodstream, propagating inflammation both periphery central nervous system. Gut dysbiosis, which results leaky intestinal barrier, exacerbates plays significant role linking pathogenesis neurodegeneration gut-brain/gut-brain-liver axis. Inflammatory states within brain can lead insulin resistance, mitochondrial dysfunction, autolysosomal increased oxidative stress. disruptions impair normal neuronal function subsequently cognitive decline motor deficits, similar pathologies observed neurodegenerative diseases, including Alzheimer's disease, multiple sclerosis, Parkinson's disease. Understanding underlying disease mechanisms crucial for developing therapeutic strategies address defects these metabolic pathways. In this review, we summarize provide insights different strategies, methods alter gut lifestyle changes, dietary supplementation, well pharmacological agents derived from natural sources, that target obesity-induced

Язык: Английский

---

Noteworthy perspectives on microglia in neuropsychiatric disorders

Journal of Neuroinflammation, Год журнала: 2023, Номер 20(1)

Опубликована: Окт. 4, 2023

Abstract Microglia are so versatile that they not only provide immune surveillance for central nervous system, but participate in neural circuitry development, brain blood vessels formation, blood–brain barrier architecture, and intriguingly, the regulation of emotions behaviors. have a profound impact on neuronal survival, wiring synaptic plasticity. As professional phagocytic cells brain, remove dead cell debris neurotoxic agents via an elaborate mechanism. The functional profile microglia varies considerately depending age, gender, disease context other internal or external environmental factors. Numerous studies demonstrated pivotal involvement neuropsychiatric disorders, including negative affection, social deficit, compulsive behavior, fear memory, pain symptoms associated with major depression disorder, anxiety autism spectrum disorder schizophrenia. In this review, we summarized latest discoveries regarding microglial ontogeny, subtypes state spectrum, biological functions mechanistic underpinnings emotional behavioral disorders. Furthermore, highlight potential microglia-targeted therapies propose outstanding questions to be addressed future research human microglia.

Язык: Английский

---

Comparison on cognitive outcomes of antidiabetic agents for type 2 diabetes: A systematic review and network meta‐analysis

Diabetes/Metabolism Research and Reviews, Год журнала: 2023, Номер 39(7)

Опубликована: Июнь 11, 2023

Abstract We aimed to summarise current evidence on different antidiabetic drugs delay cognitive impairment, including mild dementia, Alzheimer's disease (AD) and vascular among subjects with type 2 diabetes mellitus (T2DM). Medline, Cochrane Embase databases were searched from inception 31 July 2022. Two investigators independently reviewed screened trials comparing no drugs, placebo, or other active outcomes in T2DM. Data analysed using meta‐analysis network meta‐analysis. Twenty‐seven studies met the inclusion criteria, 3 randomised controlled trials, 19 cohort 5 case‐control studies. Compared non‐user, SGLT‐2i (OR 0.41 [95% CI 0.22–0.76]), GLP‐1RA 0.34 0.14–0.85]), thiazolidinedione 0.60 0.51–0.69]), DPP‐4i 0.78 0.61–0.99]) users had a decreased risk of whereas sulfonylurea 1.43 1.11–1.82]) increased dementia risk. Network showed that was most likely rank best (SUCRA = 94.4%), GLP‐1 RA second 92.7%), third 74.7%) fourth 54.9%), while worst 20.0%) for decreasing outcomes, by synthesising direct indirect comparisons multiple intervention. Evidence suggests effects ≈ RAs > delaying AD associated highest These findings provide evaluating optional treatment clinical practice. PROSPERO Registration no. CRD42022347280.

Язык: Английский

---

Signaling pathways and intervention for therapy of type 2 diabetes mellitus

MedComm, Год журнала: 2023, Номер 4(3)

Опубликована: Июнь 1, 2023

Type 2 diabetes mellitus (T2DM) represents one of the fastest growing epidemic metabolic disorders worldwide and is a strong contributor for broad range comorbidities, including vascular, visual, neurological, kidney, liver diseases. Moreover, recent data suggest mutual interplay between T2DM Corona Virus Disease 2019 (COVID-19). characterized by insulin resistance (IR) pancreatic β cell dysfunction. Pioneering discoveries throughout past few decades have established notable links signaling pathways pathogenesis therapy. Importantly, number substantially control advancement core pathological changes in T2DM, IR dysfunction, as well additional pathogenic disturbances. Accordingly, an improved understanding these sheds light on tractable targets strategies developing repurposing critical therapies to treat its complications. In this review, we provide brief overview history pathways, offer systematic update role mechanism key underlying onset, development, progression T2DM. content, also summarize current therapeutic drugs/agents associated with treatment complications, discuss some implications directions future field.

Язык: Английский

---