Introduction
thrombosis, death, neuroinflammation, TNF-α, brain amyloid, stroke, dementia, gastrointestinal tract, Alzheimer’s disease, neuronal loss, AD, Alzheimer
THROMBOSIS, STROKE, PROGRESSIVE NEURODEGENERATIVE DISORDER, OXIDATIVE STRESS, HYPERTENSION, ALZHEIMER
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. Considerable research efforts have been directed towards developing safe and effective pharmacological treatments. The U.S. Food and Drug Administration (FDA) has approved seven drugs for the treatment of Alzheimer’s: rivastigmine, galantamine, donepezil, memantine, memantine plus donepezil, aducanumab (under the accelerated approval pathway), and lecanemab [Lecanemab, the last drug approved by the FDA, reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months according Clarity AD trial [Erythropoietin (EPO) is a growth factor mainly produced in the kidney and with a well-known activity on erythropoiesis. The EPO receptor (EPOR) is differentially expressed in neurons, astrocytes, and endothelial cells in different regions of the central nervous system (CNS) [EPO binding to its cell surface receptor leads to a decrease in apoptosis, oxidative stress, and neuroinflammation. Studies have shown that EPO protects hippocampal and cortical neurons from glutamate-induced cell death in vitro and in vivo [When administered intravenously, EPO can result in hypertension, thrombosis, and stroke [NeuroEPO plus (NeuralCIMThe reduction in sialic acid causes rapid hepatic degradation, and thus neuroEPO plus needs to be administered by the intranasal route to avoid hepatic first pass metabolism and degradation in the gastrointestinal tract [In the ICV-Aβ25-35 AD mice model and in the aged transgenic mice model Tg2576, neuroEPO plus prevented neuronal loss in the hippocampal CA1 region, reduced the number of brain amyloid plaques, reduced the increment of TNF-α, IL-1β levels, glial activation, neuroinflammation, oxidative effects, and apoptosis in neurons and, also, significantly improved spatial memory [Direct evidence of neuroEPO plus in the CNS has been demonstrated in NeuroEPO plus has been safely evaluated in healthy volunteers [