An analysis of the peptide composition of a 'light' peptide fraction of cerebrolysin

This study was the first to compare the neuroprotective activity of Cerebrolysin®, Actovegin® and Cortexin® in rodent models of acute and chronic brain ischemia. The neuroprotective action was evaluated in animals with acute (middle cerebral artery occlusion) or chronic (common carotid artery stenosis) brain ischemia models in male rats. Cortexin® (1 or 3 mg/kg/day), Cerebrolysin® (538 or 1614 mg/kg/day) and Actovegin® (200 mg/kg/day) were administered for 10 days. To assess the neurological and motor impairments, open field test, adhesive removal test, rotarod performance test and Morris water maze test were performed. Brain damage was assessed macro- and microscopically, and antioxidant system activity was measured in brain homogenates. In separate experiments in vitro binding of Cortexin® to a wide panel of receptors was assessed, and blood-brain barrier permeability of Cortexin® was assessed in mice in vivo. Cortexin® or Cerebrolysin® and, to a lesser extent, Actovegin® improved the recovery of neurological functions, reduced the severity of sensorimotor and cognitive impairments in rats. Cortexin® reduced the size of necrosis of brain tissue in acute ischemia, improved functioning of the antioxidant system and prevented the development of severe neurodegenerative changes in chronic ischemia model. Radioactively labeled Cortexin® crossed the blood-brain barrier in mice in vivo with concentrations equal to 6–8% of concentrations found in whole blood. During in vitro binding assay Cortexin® (10 μg/ml) demonstrated high or moderate binding to AMPA-receptors (80.1%), kainate receptors (73.5%), mGluR1 (49.0%), GABAA1 (44.0%) and mGluR5 (39.7%), which means that effects observed in vivo could be related on the glutamatergic and GABAergic actions of Cortexin®. Thus, Cortexin, 1 or 3 mg/kg, or Cerebrolysin®, 538 or 1614 mg/kg, were effective in models acute and chronic brain ischemia in rats. Cortexin® contains compounds acting on AMPA, kainate, mGluR1, GABAA1 and mGluR5 receptors in vitro, and readily crosses the blood-brain barrier in mice.

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“…similar in the production method, but significantly differ in their qualitative and quantitative composition [30,31].…”

Section: Plos Onementioning

confidence: 99%

Neuroprotective action of Cortexin, Cerebrolysin and Actovegin in acute or chronic brain ischemia in rats

et al. 2021

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“…Low-molecular-weight peptide fragments present in the Cerebrolysin preparation can cross the BBB, exert similar effects after peripheral and intracerebral administration, act like endogenous neurotrophic factors, and modulate multiple signaling pathways, probably through synergistic actions of various peptides. [142][143][144][145][146][147][148] In this way, Cerebrolysin acts as a neurotrophic drug with positive pleiotropic effects on Aβ and tau pathologies, neuroinflammation, endogenous neurotrophic factors, oxidative stress, excitotoxicity, neurotransmission, brain metabolism, neuronal apoptosis and degeneration, neuroplasticity, neurogenesis, and cognition in investigational models and in AD patients. The PI3K/Akt signaling pathway and enzymes such as GSK3β, CDK5, BACE1 (APP β-secretase) and the Aβ degrading enzyme Neprilysin have been involved in the reductions of Aβ and Tau pathology induced by Cerebrolysin, and in some of its neuroprotective effects.…”

Section: Pharmacology and Mode Of Action Of Cerebrolysinmentioning

confidence: 99%

“…The solution contains 215.2 mg/ml of the active pharmaceutical ingredient Cerebrolysin concentrate. Low‐molecular‐weight peptide fragments present in the Cerebrolysin preparation can cross the BBB, exert similar effects after peripheral and intracerebral administration, act like endogenous neurotrophic factors, and modulate multiple signaling pathways, probably through synergistic actions of various peptides 142–148 . In this way, Cerebrolysin acts as a neurotrophic drug with positive pleiotropic effects on Aβ and tau pathologies, neuroinflammation, endogenous neurotrophic factors, oxidative stress, excitotoxicity, neurotransmission, brain metabolism, neuronal apoptosis and degeneration, neuroplasticity, neurogenesis, and cognition in investigational models and in AD patients 142 …”

Section: Multitarget Neurotrophic Treatment With Cerebrolysin In Admentioning

confidence: 99%

Cerebrolysin in the therapy of mild cognitive impairment and dementia due to Alzheimer's disease: 30 years of clinical use

Гаврилова

Álvarez

2020

Medicinal Research Reviews

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Alzheimer's disease (AD) is the most common neurocognitive disorder and a global health problem. The prevalence of AD is growing dramatically, especially in low-and middle-income countries, and will reach 131.5 million cases worldwide by 2050. Therefore, developing a disease-modifying therapy capable of delaying or even preventing the onset and progression of AD has become a world priority, and is an unmet need. The pathogenesis of AD, considered as the result of an imbalance between resilience and risk factors, begins many years before the typical clinical picture develops and involves multiple pathophysiological mechanisms. Since the pathophysiology of AD is multifactorial, it is not surprising that all attempts done to modify the disease course with drugs directed towards a single therapeutic target have been unsuccessful. Thus, combined modality therapy, using multiple drugs with a single mechanism of action or multi-target drugs, appears as the most promising strategy for both effective AD therapy and prevention. Cerebrolysin, acting as a multitarget peptidergic drug with a neurotrophic mode of action, exerts long-lasting therapeutic effects on AD that could reflect its potential utility for disease modification. Clinical trials demonstrated that Cerebrolysin is safe and efficacious in the treatment of AD, and may enhance and prolong the efficacy of cholinergic drugs, particularly in moderate to advanced AD patients. In this review, we summarize advances of therapeutic relevance in the pathogenesis and the biomarkers of

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Geroprotective properties of neuroprotective and neurotrophic peptides

Громова

Torshin

Zgoda

et al. 2020

RJTAO

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Цель исследования-выяснение наличия в составе церебролизина пептидных фрагментов, способствующих геропротекции. Материал и методы. Проведен комплексный масс-спектрометрический анализ пептидного состава церебролизина с последующей системно-биологической оценкой. Результаты и обсуждение. В мультипептидном составе церебролизина выделены 36 пептидов, которые могут проявлять геропротективные свойства. Эти пептиды включают пептиды-миметики адреномедуллина и энкефалинов, пептиды-ингибиторы семи таргетных белков человека (протеинкиназы MAPK1, VPRBP и PKC, гамма-секретазы PS1, киназы CDK1, SGK1 и mTOR). Показано, что установленные пептиды церебролизина могут являться конкурентными ингибиторами семи таргетных белков. В частности, ингибирование PKC и mTOR стимулирует усиление аутофагии (процесса утилизации отработанных и абнормальных белков), что способствует увеличению продолжительности жизни клеток и модельных организмов. Заключение. Церебролизин может проявлять геропротективные эффекты посредством ингибирования семи таргетных белков, активации эндорфинергической нейротрансмиссии и опосредованной нормализации тонуса сосудов.

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An analysis of the peptide composition of a 'light' peptide fraction of cerebrolysin

Cited by 9 publications

References 33 publications

Neuroprotective action of Cortexin, Cerebrolysin and Actovegin in acute or chronic brain ischemia in rats

Neuroprotective action of Cortexin, Cerebrolysin and Actovegin in acute or chronic brain ischemia in rats

Cerebrolysin in the therapy of mild cognitive impairment and dementia due to Alzheimer's disease: 30 years of clinical use

Geroprotective properties of neuroprotective and neurotrophic peptides

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