Current Evidence on the Protective Effects of Recombinant Human Erythropoietin and Its Molecular Variants against Pathological Hallmarks of Alzheimer’s Disease

Pharmaceuticals

Deisy Gasca-Martínez¹  JoséJ. Jarero-Basulto²  MarthaC. Rivera-Cervantes²  Francisco García-Sierra³  Yadira Gasca-Martínez⁴  Carlos Beas-Zárate⁴ 

[1] Behavioral Analysis Unit, Neurobiology Institute, Campus UNAM-Juriquilla, Querétaro 76230, Mexico;Cellular Neurobiology Laboratory, Cell and Molecular Biology Department, CUCBA, University of Guadalajara, Zapopan 45220, Mexico;Department of Cell Biology, Center of Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV), Ciudad de Mexico 07360, Mexico;Development and Neural Regeneration Laboratory, Cell and Molecular Biology Department, CUCBA, University of Guadalajara, Zapopan 45220, Mexico;

关键词: Alzheimer’s disease;    erythropoietin;    protective effects;    neuroinflammation;    apoptosis;    oxidative stress;   

DOI  :  10.3390/ph13120424

来源: DOAJ

【 摘 要 】

Substantial evidence in the literature demonstrates the pleiotropic effects of the administration of recombinant human erythropoietin (rhEPO) and its molecular variants in different tissues and organs, including the brain. Some of these reports suggest that the chemical properties of this molecule by itself or in combination with other agents (e.g., growth factors) could provide the necessary pharmacological characteristics to be considered a potential protective agent in neurological disorders such as Alzheimer’s disease (AD). AD is a degenerative disorder of the brain, characterized by an aberrant accumulation of amyloid β (Aβ) and hyperphosphorylated tau (tau-p) proteins in the extracellular and intracellular space, respectively, leading to inflammation, oxidative stress, excitotoxicity, and other neuronal alterations that compromise cell viability, causing neurodegeneration in the hippocampus and the cerebral cortex. Unfortunately, to date, it lacks an effective therapeutic strategy for its treatment. Therefore, in this review, we analyze the evidence regarding the effects of exogenous EPOs (rhEPO and its molecular variants) in several in vivo and in vitro Aβ and tau-p models of AD-type neurodegeneration, to be considered as an alternative protective treatment to this condition. Particularly, we focus on analyzing the differential effect of molecular variants of rhEPO when changes in doses, route of administration, duration of treatment or application times, are evaluated for the improved cellular alterations generated in this disease. This narrative review shows the evidence of the effectiveness of the exogenous EPOs as potential therapeutic molecules, focused on the mechanisms that establish cellular damage and clinical manifestation in the AD.

【 授权许可】

Unknown