Neuroprotective effects of geniposide in the MPTP mouse model of Parkinson's disease

Chen, YiMei; Zhang, Yanfang; Li, Lin; Hölscher, Christian

doi:10.1016/j.ejphar.2015.09.029

Cited by 93 publications

(52 citation statements)

References 44 publications

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“…Moreover, exendin-4 reverses biochemical and behavioral deficits in a pre-motor rodent model of PD with combined noradrenergic and serotonergic lesions (Rampersaud et al, 2012). Furthermore, some authors also found that MPTP-treated mice, another typical PD mice model, were protected by exendin-4 (Li et al, 2009), Val(8)GLP-1-glu-PAL , liraglutide (Liu et al, 2015a), lixisenatide (Liu et al, 2015a), and geniposide (Chen et al, 2015b) against nigrostriatal damage. Thus, GLP-1-based therapies may be used as a possible therapy for the motor and/or nonmotor symptoms prominent in the early stages of PD.…”

Section: Effects Of Glp-1 On Neurodegenerative Diseasementioning

confidence: 89%

Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases

Hölscher

2016

Reviews in the Neurosciences

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AbstractIncretin hormones include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Due to their promising action on insulinotropic secretion and improving insulin resistance (IR), incretin-based therapies have become a new class of antidiabetic agents for the treatment of type 2 diabetes mellitus (T2DM). Recently, the links between neurodegenerative diseases and T2DM have been identified in a number of studies, which suggested that shared mechanisms, such as insulin dysregulation or IR, may underlie these conditions. Therefore, the effects of incretins in neurodegenerative diseases have been extensively investigated. Protease-resistant long-lasting GLP-1 mimetics such as lixisenatide, liraglutide, and exenatide not only have demonstrated promising effects for treating neurodegenerative diseases in preclinical studies but also have shown first positive results in Alzheimer’s disease (AD) and Parkinson’s disease (PD) patients in clinical trials. Furthermore, the effects of other related incretin-based therapies such as GIP agonists, dipeptidyl peptidase-IV (DPP-IV) inhibitors, oxyntomodulin (OXM), dual GLP-1/GIP, and triple GLP-1/GIP/glucagon receptor agonists on neurodegenerative diseases have been tested in preclinical studies. Incretin-based therapies are a promising approach for treating neurodegenerative diseases.

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Section: Effects Of Glp-1 On Neurodegenerative Diseasementioning

confidence: 89%

Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases

Hölscher

2016

Reviews in the Neurosciences

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“…24 These effects include inhibitory effects on inflammation, 5,8 promotion of mitochondrial biogenesis, 25,26 neurotrophic effects, 27,28 stimulation of neurogenesis, 7 and restoration of neuronal insulin signalling. 29 Whether some or all of these mechanisms contributed to the clinical effects in our study cannot be definitively established, but one or several of these mechanisms could have acted in synergy to promote cell survival, preserve compensatory responses, and prevent maladaptive responses.…”

Section: Discussionmentioning

confidence: 99%

Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial

et al. 2017

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Summary Background Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has neuroprotective effects in preclinical models of Parkinson’s disease. We investigated whether these effects would be apparent in a clinical trial. Methods In this single-centre, randomised, double-blind, placebo-controlled trial, patients with moderate Parkinson’s disease were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg or placebo once weekly for 48 weeks in addition to their regular medication, followed by a 12-week washout period. Eligible patients were aged 25–75 years, had idiopathic Parkinson’s disease as measured by Queen Square Brain Bank criteria, were on dopaminergic treatment with wearing-off effects, and were at Hoehn and Yahr stage 2·5 or less when on treatment. Randomisation was by web-based randomisation with a two strata block design according to disease severity. Patients and investigators were masked to treatment allocation. The primary outcome was the adjusted difference in the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor subscale (part 3) in the practically defined off-medication state at 60 weeks. All efficacy analyses were based on a modified intention-to-treat principle, which included all patients who completed any post-randomisation follow-up assessments. The study is registered at ClinicalTrials.gov (NCT01971242) and is completed. Findings Between June 18, 2014, and March 13, 2015, 62 patients were enrolled and randomly assigned, 32 to exenatide and 30 to placebo. Our primary analysis included 31 patients in the exenatide group and 29 patients in the placebo group. At 60 weeks, off-medication scores on part 3 of the MDS-UPDRS had improved by 1·0 points (95% CI −2·6 to 0·7) in the exenatide group and worsened by 2·1 points (−0·6 to 4·8) in the placebo group, an adjusted mean difference of −3·5 points (−6·7 to −0·3; p=0·0318). Injection site reactions and gastrointestinal symptoms were common adverse events in both groups. Six serious adverse events occurred in the exenatide group and two in the placebo group, although none in either group were judged to be related to the study interventions. Interpretation Exenatide had positive effects on practically defined off-medication motor scores in Parkinson’s disease, which were sustained beyond the period of exposure. Whether exenatide affects the underlying disease pathophysiology or simply induces long-lasting symptomatic effects is uncertain. Exenatide represents a major new avenue for investigation in Parkinson’s disease, and effects on everyday symptoms should be examined in longer-term trials. Funding Michael J Fox Foundation for Parkinson’s Research.

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“…Приме-нение ингибиторов ДПП-4 и аналогов ГПП-1 защи-щало митохондрии, повышая активность комплекса I дыхательной цепи и противоапоптотического бел-ка Bcl-2 с последующим снижением активности ка-спазы 3, что в конечном итоге приводило к сохране-нию дофаминергических нейронов при моделиро-вании БП [31,34]. Механизм подобного эффекта связывают с активацией сигнальных путей ГПП-1Р/ PI3K/PKB (Akt) и ГПП-1Р/АЦ/PKA: -PKB (Akt) инактивирует транскрипционный фактор FOXO1 (см.…”

Section: функциональное состояние митохондрий и апоптозunclassified

Neuroprotective properties of incretin mimetics in brain ischemia and neurodegenerative diseases

Tyurenkov¹,

Бакулин²,

Куркин³

et al. 2017

Probl Endokrinol (Mosk)

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Волгоградский государственный медицинский университет, Волгоград, Россия Сахарный диабет 2-го типа (СД2) -заболевание, существенно увеличивающее риск нейродегенеративных заболеваний и инсульта. Значительный рост числа пациентов с СД2 на фоне старения населения определяет большой интерес к противо-диабетическим препаратам, которые, помимо гипогликемического действия, способны снижать риск сердечно-сосуди-стых и нейродегенеративных заболеваний. Согласно результатам клинических исследований, у пациентов с СД2 инкретиномиметики значительно уменьшают уро-вень гликированного гемоглобина, а также умеренно снижают артериальное давление и массу жировой ткани. Аналоги глюкагоноподобного пептида-1 (ГПП-1) при добавлении их к стандартной гипогликемической терапии значимо снижают риск сердечно-сосудистых осложнений у пациентов с СД2. Отмечается позитивное действие этих препаратов у пациентов с нейродегенеративными заболеваниями, как самостоятельными, так и возникающими на фоне СД2. В настоящее время проводятся клинические исследования влияния аналогов ГПП-1 при болезни Паркинсона и Альцгеймера. Имеющиеся данные говорят о наличии у инкретиномиметиков нейропротективных свойств, которые реализуются благо-даря присутствию рецепторов ГПП-1 на нейронах, клетках микроглии и эндотелиоцитах. Установлена способность этих рецепторов запускать важнейшие внутриклеточные сигнальные пути, поддерживающие функциональную активность клет-ки и ингибирующие апоптоз в патологических условиях. В обзоре представлены результаты исследований нейропротективных свойств препаратов с инкретиномиметическим ме-ханизмом действия. Приведены данные об их влиянии на ряд патологических процессов при нейродегенеративных за-болеваниях и нарушениях мозгового кровообращения. Показана способность инкретиномиметиков снижать активацию микроглии, выработку провоспалительных цитокинов, патологическую агрегацию белков и тормозить процессы апоптоза нейронов, а также улучшать функциональное состояние митохондрий, увеличивать экспрессию трофических факторов и стимулировать нейрогенез.Ключевые слова: cахарный диабет; инкретины; нейропротекция; нейродегенеративные заболевания; инсульт; эксенатид; лираглутид. Neuroprotective properties of incretin mimetics in brain ischemia and neurodegenerative diseases© Ivan N. Tyurenkov, Dmitry A. Bakulin, Denis V. Kurkin, Elena V. Volotova Volgograd State Medical University, Volgograd, Russia Type 2 diabetes mellitus (DMT2) is a disease significantly increasing the risk of neurodegenerative disorders and stroke. The keen interest in anti-diabetic medications, which can reduce the risk of cardiovascular and neurodegenerative disorders, is caused by the substantial rise in the number of patients with DMT2 as a result of population aging. According to the clinical trial data, incretin mimetics significantly reduce the glycosylated hemoglobin level, while moderately reducing blood pressure and adipose tissue mass in DMT2patients. When added to the conventional hypoglycemic therapy, analogues of glucagon-like peptide-1 (GLP-1) significantly dec...

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Neuroprotective effects of geniposide in the MPTP mouse model of Parkinson's disease

Cited by 93 publications

References 44 publications

Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases

Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases

Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial

Neuroprotective properties of incretin mimetics in brain ischemia and neurodegenerative diseases

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