Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Multimodal beneficial effects of BNN27, a nerve growth factor synthetic mimetic, in the 5xFAD mouse model of Alzheimer's disease
Δημιουργός/Συγγραφέας:	Kokkali, Maria Karali, Kanelina Thanou, Evangelia Papadopoulou, Maria Anna Zota, Ioanna Tsimpolis, Alexandros Efstathopoulos, Paschalis [EL] Καλογεροπούλου, Θεοδώρα[EN] Calogeropoulou, Theodora Li, Ka Wan Sidiropoulou, Kyriaki Gravanis, Achille Charalampopoulos, Ioannis
Ημερομηνία:	2024-11-25
Γλώσσα:	Αγγλικά
ISSN:	1359-4184 1476-5578
DOI:	10.1038/s41380-024-02833-w
Άλλο:	39587294
Περίληψη:	Alzheimer's Disease (AD) is an incurable and debilitating progressive, neurodegenerative disorder which is the leading cause of dementia worldwide. Neuropathologically, AD is characterized by the accumulation of Aβ amyloid plaques in the microenvironment of brain cells and neurovascular walls, chronic neuroinflammation, resulting in neuronal and synaptic loss, myelin and axonal failure, as well as significant reduction in adult hippocampal neurogenesis. The hippocampal formation is particularly vulnerable to this degenerative process, due to early dysfunction of the cholinergic circuit. Neurotrophic factors consist major regulatory molecules and their decline in AD is considered as an important cause of disease onset and progression. Novel pharmacological approaches are targeting the downstream pathways controlled by neurotrophins, such as nerve growth factor (NGF) receptors, TrkA and p75NTR, which enhance hippocampal neurogenic capacity and neuroprotective mechanisms, and potentially counteract the neurotoxic effects of amyloid deposition. BNN27 is a non-toxic, newly developed 17-spiro-steroid analog, penetrating the blood-brain-barrier (BBB) and mimicking the neuroprotective effects of NGF, acting as selective activator of its receptors, both TrkA and p75NTR, thus promoting survival of various neuronal cell types. Our present research aims at determining whether and which aspects of the AD-related pathology, BNN27 is able to alleviate, exploring the cellular and molecular AD components and link these changes with improvements in the cognitive performance of an animal AD model, the 5xFAD mice. Our results clearly indicate that BNN27 administration significantly reduced amyloid-β load in whole brain of the animals, enhanced adult hippocampal neurogenesis, restored cholinergic function and synaptogenesis, reducing inflammatory activation and leading to significant restoration of cognitive functions. BNN27 may represent a new lead multimodal molecule with neuroprotective, neurogenic and anti-neuroinflammatory actions for developing druggable anti-Alzheimeric agents. Proteomics data are available via ProteomeXchange with the identifier PXD044699.
Τίτλος πηγής δημοσίευσης:	Molecular psychiatry
Θεματική Κατηγορία:	[EL] Νευροεπιστήμη. Βιολογική ψυχιατρική. Νευροψυχιατρική[EN] Neurosciences. Biological psychiatry. Neuropsychiatry [EL] Θεραπευτική. Φαρμακολογία[EN] Therapeutics.Pharmacology [EL] Βιοχημεία[EN] Biochemistry [EL] Φυσιολογία[EN] Physiology
Λέξεις-Κλειδιά:	Alzheimer's disease dementia neurodegeneration cognitive decline memory loss
EU Grant:	Operational Program Competitiveness, Entrepreneurship and Innovation (EPANEK) 1st Call for H.F.R.I. Research Projects Marie Skłodowska-Curie Actions EIC-2022-PATHFINDEROPEN-01 National Flagship Action "Hellenic Precision Medicine Network in Neurodegenerative Diseases"
EU Grant identifier:	T1EDK-03186 2301 765704 101099145
Κάτοχος πνευματικών δικαιωμάτων:	© The Author(s) 2024
Όροι και προϋποθέσεις δικαιωμάτων:	Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creativecommons.org/licenses/by-nc-nd/4.0/.
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://doi.org/10.1038/s41380-024-02833-w
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο