Short erythropoietin-derived peptide enhances memory, improves long-term potentiation, and counteracts amyloid beta-induced pathology.

Autor: Dmytriyeva O; Laboratory of Neural Plasticity, Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark; Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark., Belmeguenai A; Lyon Neuroscience Research Center, TIGER Team, Bron, France; Epilepsy Institute IDÉE, Bron, France., Bezin L; Lyon Neuroscience Research Center, TIGER Team, Bron, France; Epilepsy Institute IDÉE, Bron, France., Soud K; Laboratory of Neural Plasticity, Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark., Drucker Woldbye DP; Laboratory of Neural Plasticity, Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark., Gøtzsche CR; Laboratory of Neural Plasticity, Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark., Pankratova S; Laboratory of Neural Plasticity, Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark; Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: stasya@sund.ku.dk.
Jazyk: angličtina
Zdroj: Neurobiology of aging [Neurobiol Aging] 2019 Sep; Vol. 81, pp. 88-101. Date of Electronic Publication: 2019 May 13.
DOI: 10.1016/j.neurobiolaging.2019.05.003
Abstrakt: Neurodegenerative disorders such as Alzheimer's disease (AD) are characterized by the irreversible neuronal loss and memory impairment, and current treatments are merely symptomatic. Erythropoietin (EPO) has been shown to possess neurotrophic, neuroprotective, anti-inflammatory, and memory-enhancing effects, which could be therapeutically beneficial in the different aspects of AD. However, the hematopoietic effect of EPO has hampered its potential as a neuroprotective and procognitive agent. In this study, we characterized a novel small peptide, NL100, derived from a conserved C-helix region of EPO. NL100 was shown to bind to the EPO receptor, induce neuritogenesis, and protect hippocampal neurons from oxidative- and Aβ 25-35 -induced neurodegeneration in vitro. Importantly, long-term NL100 treatment did not induce hematopoiesis, overcoming this challenge associated with EPO. Memory-enhancing effects were demonstrated after NL100 treatment in social recognition test for short-term memory, in both healthy rats and rats challenged centrally with Aβ 25-35 peptide, and in the Morris water maze test for spatial memory. Moreover, NL100 was shown to reverse Aβ 25-35 -induced hippocampal degeneration and gliosis as well as pilocarpine-induced suppression of long-term potentiation in rats. In conclusion, NL100 is a novel EPO-derived nonhematopoietic peptide with neuroprotective and memory-enhancing effects and could therefore be a potential candidate for the development of new treatments for neurodegenerative disorders and dementia.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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