Derived from the hormone erythropoietin (EPO), which promotes the synthesis of red blood cells, ARA 290 is a non-erythropoietic peptide. It is a synthetic analog of a naturally occurring hormone with alleged neuroprotective properties. Data suggests that ARA 290 may be useful in the context of neurological disorders. Research suggests that after successfully crossing the blood-brain barrier, ARA 290 may enter the CNS.
Because of this property, ARA 290 has been studied for its possible research properties in various CNS illnesses, including those affecting the brain and spinal cord. Research in animal models of brain injury and Alzheimer’s disease has purported that ARA 290 may ease inflammation, damage, and cognitive impairment. Not only does ARA 290 suggest promise as an adjuvant, but it may also have many positive properties on brain cells, such as promoting neurogenesis (the process of creating new neurons) and protecting existing neurons from harm.
ARA 290 Peptide: What is it?
The A2A receptor is a subtype of the adenosine receptors, and ARA 290 is a specific antagonist of this subtype. The brain is home to many G protein-coupled receptors (GPCRs) that play a vital role in many physiological processes, including controlling blood flow, releasing neurotransmitters, and the excitability of neurons. In the striatum, a brain region involved in motor control and reward-related behaviors, the A2A receptors are crucial in controlling dopamine levels.
According to current thinking, ARA 290 may potentially increase dopamine levels and improve dopamine-mediated activities, including movement and motivation, by blocking A2A receptors in the striatum. Furthermore, ARA 290 has been hypothesized to modulate the actions of other neurotransmitters, including GABA and glutamate.
Animal models of Parkinson’s disease and schizophrenia have indicated that ARA 290 may be effective in alleviating motor symptoms and cognitive and negative symptoms, respectively, in preclinical investigations.
It has been theorized in the literature that ARA 290 may target:
- Parkinson’s disease -ARA 290 is being researched to see whether it might enhance the efficacy of Levodopa, the prevailing substance for the condition. By elevating striatal dopamine levels, ARA 290 has been speculated to alleviate motor symptoms associated with Parkinson’s disease.
- Cognitive and negative symptoms of schizophrenia- Memory, attention, and decision-making issues are examples of cognitive symptoms; in contrast, negative symptoms include social disengagement, indifference, and lack of drive. Some propose that ARA 290 may alleviate these symptoms by influencing the release of certain neurotransmitters.
- Neuropathy –ARA 290 has ascertained effectiveness in clinical and preclinical metabolic regulation and neuropathy investigations. Research on research models with type 2 diabetes has hinted that it may help with both metabolic management and neuropathy.
ARA-290 Peptide and Erythropoietin
The cytoprotective effect on non-hematopoietic tissues is a recent discovery of erythropoietin (EPO), the primary erythropoiesis-stimulating factor often used to manage anemia. Epo demonstrated its BBB-crossing capabilities and mammalian brain expression within this framework. Neurogenesis stimulation, cognitive improvement, and activation of anti-apoptotic, antioxidant, and anti-inflammatory signaling pathways have all been suggested in clinical studies using recombinant Epo therapy. Novel insights into the pharmacological potencies of Epo were provided by these processes, which were postulated to define a neuroprotective characteristic. Nevertheless, several inquiries concern the environmental or physiological variables that trigger the development of Epo and its potential physiological function in the CNS.
Thromboembolic problems linked to increases in hematocrit and blood viscosity may occur during long-term therapies, especially when large concentrations of Epo are required, even if Epo is a promising option in the context of neuronal injury. This profile seems to be matched by carbamylated erythropoietin and other compounds, such as Epo fusion proteins and incomplete peptides of Epo. Experimental data relating to erythropoietin and central nervous system function has been published recently to discover improvements in the context of neurodegenerative illnesses. This review will concentrate on the discussion of these findings. To top it all off, the neuroprotective potential of Epo will be better understood and enhanced after a study of the suggested pathways for new derivatives.
ARA-290 Peptide and Depression
There is some data suggesting that erythropoietin (EPO) may have antidepressant properties based on studies of its effects on the nervous system. An EPO-analog peptide called ARA-290 has been hypothesized to have neurotrophic and antidepressant properties without the hematological effects. This research set out to examine ARA-290’s potential antidepressant effects using a neuropsychological model of medication action.
In a randomized, parallel-group, double-blind study, 36 healthy research models were given either ARA290 or a placebo. Cognitive and neural effects were evaluated one week after delivery. Neuronal processing of sad versus joyful and behavioral detection of emotional reactions were the main outcome measures.
Research models given ARA-290 appeared to display reduced fusiform gyrus activation. ARA-290 seemed to have a dampening effect on the ability to identify dissatisfied and joyful faces. Although ARA-290 did not appear to improve memory for positive words, it did seem to speed up distinguishing between positive and negative terms. Last but not least, ARA-290 has been theorized to have shifted focus to more upbeat, emotionally charged images. Affective symptoms and mood appeared to be unaffected.
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References:
[i] Daniela C. Vittori, María E. Chamorro, Yender V. Hernández, Romina E. Maltaneri, Alcira B. Nesse. Erythropoietin and derivatives: Potential beneficial effects on the brain. Journal of Neurochemistry. 19 July 2021. https://doi.org/10.1111/jnc.15475.
[ii] Hilâl Cerit, Ilya M. Veer, Albert Dahan, Marieke Niesters, Catherine J. Harmer, Kamilla W. Miskowiak, Serge A.R.B. Rombouts, Willem Van der Does, Testing the antidepressant properties of the peptide ARA290 in a human neuropsychological model of drug action, European Neuropsychopharmacology, Volume 25, Issue 12, 2015, Pages 2289-2299, ISSN 0924-977X,
[iii] Marieke Niesters, Maarten Swartjes, Lara Heij, Michael Brines, Anthony Cerami, Ann Dunne, Elske Hoitsma &Albert Dahan. The erythropoietin analog ARA 290 for treatment of sarcoidosis-induced chronic neuropathic pain. Expert Opinion on Orphan Druges. Volume 1, 2013, Issue 1. Pages 77-87 | Published online: 17 Dec 2012.
[iv] Brines, M., Dunne, A.N., van Velzen, M. et al. ARA 290, a Nonerythropoietic Peptide Engineered from Erythropoietin, Improves Metabolic Control and Neuropathic Symptoms in Patients with Type 2 Diabetes. Mol Med 20, 658–666 (2014).
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