Neuroprotective Effects of Tripeptides

Alzheimer’s disease is a neurodegenerative disease that affects older adults and causes dementia. Progressive cognitive impairment is a hallmark of this condition. Globally, AD incidence is growing exponentially. According to predictions, the number of people with dementia will increase to 131.5 million across the globe by 2050.

Alzheimer’s disease comes in several forms, the most common of which is late-onset AD (LOAD), with the age of onset being over 65. Alternatively, early-onset AD (EOAD) occurs in around 1% to 6% of patients with AD and has an onset age between 35 and 65 years.

The disease is genetically classified into familial cases (FAD) and sporadic cases (SAD). A mutation in one of three genes causes familial Alzheimer’s disease: amyloid precursor protein (APP), presenilin 2 (PSEN2), presenilin 1 (PSEN1). Alternatively, sporadic AD develops due to a combination of genetic and environmental factors.

Nowadays, the exact molecular mechanisms of AD pathogenesis remain obscure. Therefore, the need exists for neuroprotective remedies that are safe, don’t cause an addiction, and are effective at the early stages of cognitive decline. The therapeutic value of short peptides for Alzheimer’s disease treatment may be a part of this approach.

Cortexin and Cerebrolysin are the first described neuroprotective peptide drugs isolated from the cerebral cortex of pigs and cattle. Studies showed that Cortexin is an effective treatment for chronic cerebral ischemia. In addition, this peptide complex aided in memory restoration in individuals suffering from acute ischemic stroke.

According to the analysis of Cerebrolysin effects conducted by the Shanghai Jiao Tong University, the administration of this peptide to Alzheimer’s disease patients resulted in significant improvements in cognitive function, non-cognitive symptoms, and daily living activities of these individuals. Notably, patients involved in this study had mild to moderately severe stages of the condition.

In another study, administration of Cerebrolysin injections to mutant mice AD models for six months decreased brain amyloid levels and improved synaptic function.

Effect of Pinealon

EDR, or Pinealon, is a tripeptide found in Cortexin. It has a neuroprotective activity similar to one of Cortexin. Combined administration of Pinealon with standard treatment to patients with craniocerebral trauma resulted in memory improvement in 59.4% of individuals involved in this study.

In addition, Pinealon aided in improving the psychoemotional state in the elderly by elevating the recovery index compared to the control group. This peptide restored the density of dendritic spines in spiny projection neurons in a laboratory model of Huntington’s disease (HD). Moreover, treatment of primary hippocampal cultures with induced AD with Pinealon increased the number of mushroom spines up to 71%.

Laboratory and animal studies of the Pinealon effect as a neuroprotector suggest potential benefits of this peptide for Alzheimer’s patients. It is due to the ability of EDR peptides to affect gene expression and the synthesis of proteins involved in the development of this disease.

Effect of Vesugen

Vesugen, or KED peptide, is a peptide contained in a polypeptide complex derived from cattle vessels. It has vasoprotective properties. Combined administration of Vesugen and Pinealon improves cognitive functions of workers in hazardous environments.

In human dental stem cells, the KED peptide enhanced the differentiation of neurons. In addition, Vesugen treatment of the laboratory model of Hanington’s disease produced an up to 32% increase in the spine density. Application of this peptide for Alzheimer’s cell culture increased the number of mushroom spines by 1.2 times. The decrease in the number of mushroom spines correlates with neuroplasticity impairments. Therefore, the administration of Vesugen on a systematic basis contributed to the restoration of neuroplasticity. It also inhibited the loss of functional synaptic connections, thereby maintaining the stability of mushroom spines.

Administration of this peptide to Alzheimer’s model mice showed that the neuroprotective effect of Vesugen may be a result of its ability to prevent degeneration of the neurovascular system. Furthermore, studies revealed that KED peptide helped restore endothelial cell growth factor (VEGF) and expression of endothelin-1 (narrows blood vessels) in aortic endothelial cells derived from patients with atherosclerosis. In addition, overexpression of neuron-specific VEGF partially reversed the cerebral vessel loss and enhanced cognitive function in an AD mouse model.

A comparative study of the effect of Vesugen and Pinealon oral administration in individuals of different ages suffering from organic brain and chronic polymorbid syndromes demonstrated higher effectiveness of KED peptide. This effect of Vesugen resulted in a more rapid recovery of cognitive functions and an increase in the patient’s biological age.

Research has previously shown that Vesugen affects the activity of genes and proteins associated with neuronal differentiation and aging. This study also found several molecular epigenetic mechanisms related to the neuroprotective properties of peptides.

Peptide treatment for Alzheimer’s disease

Tripeptides play a role in regulating the expression of some genes involved in synaptic pathology, neuroplasticity, and cognitive impairment in Alzheimer’s disease. This ability of peptides may explain the molecular mechanism of their neuroprotective effects.

To conclude, the neuroprotective effect of Pinealon and Vesugen peptides on Alzheimer’s disease treatment is based on their ability to prevent dendritic spine degeneration and neuronal plasticity impairments at the epigenetic level. Researchers suppose that the effect of Pinealon results from its influence on the brain’s neurons. Additionally, the Vesugen peptide impacts Alzheimer’s disease at two levels: dysfunction of the cerebral vessels and loss of neurons. Therefore, further study of the effect of Vesugen and Pinealon could lead to the development of neuroprotective drugs for the prevention and treatment of Alzheimer’s disease in its early stage.

You can learn more about the different types of peptides and their functions by Click Here.

In light of the latest findings, it is possible that beta-amyloid protein might not be the key explanation for Alzheimer’s disease. Therefore, targeting amyloid oligomers is still a questionable way of treating the disorder. All clinical trials focusing on it have not shown any effective results so far. In addition, promising data from previous research on *56 species of amyloid (DOI: 10.1038/nature04533) has shown to be invalid. Amyloid protein may still play a role in Alzheimer’s disease but likely in a different form than it was proposed before. You can read more about it in Derek Lowe’s commentary on the topic in his editorially independent blog about drug discovery and the pharma industry: https://www.science.org/content/blog-post/faked-beta-amyloid-data-what-does-it-mean 

Source:

Khavinson, V., Ilina, A., Kraskovskaya, N., Linkova, N., Kolchina, N., Mironova, E., Erofeev, A., & Petukhov, M. (2021). Neuroprotective Effects of Tripeptides-Epigenetic Regulators in Mouse Model of Alzheimer’s Disease. Pharmaceuticals (Basel, Switzerland), 14(6), 515. https://doi.org/10.3390/ph14060515