Increased P2×2 receptors induced by amyloid-β peptide participates in the neurotoxicity in alzheimer’s disease

Amyloid beta peptide (Aβ) is tightly associated with the physiopathology of Alzheimer’s Disease (AD) as one of the most important factors in the evolution of the pathology. In this context, we previously reported that Aβ increases the expression of ionotropic purinergic receptor 2 (P2×2R). However,...
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Autor*in:	Pamela A. Godoy [verfasserIn] Daniela Mennickent [verfasserIn] Inmaculada Cuchillo-Ibáñez [verfasserIn] Oscar Ramírez-Molina [verfasserIn] Tiare Silva-Grecchi [verfasserIn] Jessica Panes-Fernández [verfasserIn] Patricio Castro [verfasserIn] Javier Sáez-Valero [verfasserIn] Jorge Fuentealba [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	P2×2 Purinergic receptors Amyloid beta Alzheimer’s disease Fe65 APP

Übergeordnetes Werk:	In: Biomedicine & Pharmacotherapy - Elsevier, 2021, 142(2021), Seite 111968-
Übergeordnetes Werk:	volume:142 ; year:2021 ; pages:111968-

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.biopha.2021.111968

Katalog-ID:	DOAJ001164902

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allfields	10.1016/j.biopha.2021.111968 doi (DE-627)DOAJ001164902 (DE-599)DOAJf03fd7d2d1614c0494836fa2ce159013 DE-627 ger DE-627 rakwb eng RM1-950 Pamela A. Godoy verfasserin aut Increased P2×2 receptors induced by amyloid-β peptide participates in the neurotoxicity in alzheimer’s disease 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Amyloid beta peptide (Aβ) is tightly associated with the physiopathology of Alzheimer’s Disease (AD) as one of the most important factors in the evolution of the pathology. In this context, we previously reported that Aβ increases the expression of ionotropic purinergic receptor 2 (P2×2R). However, its role on the cellular and molecular Aβ toxicity is unknown, especially in human brain of AD patients. Using cellular and molecular approaches in hippocampal neurons, PC12 cells, and human brain samples of patients with AD, we evaluated the participation of P2×2R in the physiopathology of AD. Here, we reported that Aβ oligomers (Aβo) increased P2×2 levels in mice hippocampal neurons, and that this receptor increases at late Braak stages of AD patients. Aβo also increases the colocalization of APP with Rab5, an early endosomes marker, and decreased the nuclear/cytoplasmic ratio of Fe65 and PGC-1α immunoreactivity. The overexpression in PC12 cells of P2×2a, but not P2×2b, replicated these changes in Fe65 and PGC-1α; however, both overexpressed isoforms increased levels of Aβ. Taken together, these data suggest that P2×2 is upregulated in AD and it could be a key potentiator of the physiopathology of Aβ. Our results point to a possible participation in a toxic cycle that increases Aβ production, Ca2+ overload, and a decrease of PGC-1α. These novel findings put the P2×2R as a key novel pharmacological target to develop new therapeutic strategies to treat Alzheimer’s Disease. P2×2 Purinergic receptors Amyloid beta Alzheimer’s disease Fe65 APP Therapeutics. Pharmacology Daniela Mennickent verfasserin aut Inmaculada Cuchillo-Ibáñez verfasserin aut Oscar Ramírez-Molina verfasserin aut Tiare Silva-Grecchi verfasserin aut Jessica Panes-Fernández verfasserin aut Patricio Castro verfasserin aut Javier Sáez-Valero verfasserin aut Jorge Fuentealba verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 142(2021), Seite 111968- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:142 year:2021 pages:111968- https://doi.org/10.1016/j.biopha.2021.111968 kostenfrei https://doaj.org/article/f03fd7d2d1614c0494836fa2ce159013 kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332221007502 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 142 2021 111968-
spelling	10.1016/j.biopha.2021.111968 doi (DE-627)DOAJ001164902 (DE-599)DOAJf03fd7d2d1614c0494836fa2ce159013 DE-627 ger DE-627 rakwb eng RM1-950 Pamela A. Godoy verfasserin aut Increased P2×2 receptors induced by amyloid-β peptide participates in the neurotoxicity in alzheimer’s disease 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Amyloid beta peptide (Aβ) is tightly associated with the physiopathology of Alzheimer’s Disease (AD) as one of the most important factors in the evolution of the pathology. In this context, we previously reported that Aβ increases the expression of ionotropic purinergic receptor 2 (P2×2R). However, its role on the cellular and molecular Aβ toxicity is unknown, especially in human brain of AD patients. Using cellular and molecular approaches in hippocampal neurons, PC12 cells, and human brain samples of patients with AD, we evaluated the participation of P2×2R in the physiopathology of AD. Here, we reported that Aβ oligomers (Aβo) increased P2×2 levels in mice hippocampal neurons, and that this receptor increases at late Braak stages of AD patients. Aβo also increases the colocalization of APP with Rab5, an early endosomes marker, and decreased the nuclear/cytoplasmic ratio of Fe65 and PGC-1α immunoreactivity. The overexpression in PC12 cells of P2×2a, but not P2×2b, replicated these changes in Fe65 and PGC-1α; however, both overexpressed isoforms increased levels of Aβ. Taken together, these data suggest that P2×2 is upregulated in AD and it could be a key potentiator of the physiopathology of Aβ. Our results point to a possible participation in a toxic cycle that increases Aβ production, Ca2+ overload, and a decrease of PGC-1α. These novel findings put the P2×2R as a key novel pharmacological target to develop new therapeutic strategies to treat Alzheimer’s Disease. P2×2 Purinergic receptors Amyloid beta Alzheimer’s disease Fe65 APP Therapeutics. Pharmacology Daniela Mennickent verfasserin aut Inmaculada Cuchillo-Ibáñez verfasserin aut Oscar Ramírez-Molina verfasserin aut Tiare Silva-Grecchi verfasserin aut Jessica Panes-Fernández verfasserin aut Patricio Castro verfasserin aut Javier Sáez-Valero verfasserin aut Jorge Fuentealba verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 142(2021), Seite 111968- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:142 year:2021 pages:111968- https://doi.org/10.1016/j.biopha.2021.111968 kostenfrei https://doaj.org/article/f03fd7d2d1614c0494836fa2ce159013 kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332221007502 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 142 2021 111968-
allfields_unstemmed	10.1016/j.biopha.2021.111968 doi (DE-627)DOAJ001164902 (DE-599)DOAJf03fd7d2d1614c0494836fa2ce159013 DE-627 ger DE-627 rakwb eng RM1-950 Pamela A. Godoy verfasserin aut Increased P2×2 receptors induced by amyloid-β peptide participates in the neurotoxicity in alzheimer’s disease 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Amyloid beta peptide (Aβ) is tightly associated with the physiopathology of Alzheimer’s Disease (AD) as one of the most important factors in the evolution of the pathology. In this context, we previously reported that Aβ increases the expression of ionotropic purinergic receptor 2 (P2×2R). However, its role on the cellular and molecular Aβ toxicity is unknown, especially in human brain of AD patients. Using cellular and molecular approaches in hippocampal neurons, PC12 cells, and human brain samples of patients with AD, we evaluated the participation of P2×2R in the physiopathology of AD. Here, we reported that Aβ oligomers (Aβo) increased P2×2 levels in mice hippocampal neurons, and that this receptor increases at late Braak stages of AD patients. Aβo also increases the colocalization of APP with Rab5, an early endosomes marker, and decreased the nuclear/cytoplasmic ratio of Fe65 and PGC-1α immunoreactivity. The overexpression in PC12 cells of P2×2a, but not P2×2b, replicated these changes in Fe65 and PGC-1α; however, both overexpressed isoforms increased levels of Aβ. Taken together, these data suggest that P2×2 is upregulated in AD and it could be a key potentiator of the physiopathology of Aβ. Our results point to a possible participation in a toxic cycle that increases Aβ production, Ca2+ overload, and a decrease of PGC-1α. These novel findings put the P2×2R as a key novel pharmacological target to develop new therapeutic strategies to treat Alzheimer’s Disease. P2×2 Purinergic receptors Amyloid beta Alzheimer’s disease Fe65 APP Therapeutics. Pharmacology Daniela Mennickent verfasserin aut Inmaculada Cuchillo-Ibáñez verfasserin aut Oscar Ramírez-Molina verfasserin aut Tiare Silva-Grecchi verfasserin aut Jessica Panes-Fernández verfasserin aut Patricio Castro verfasserin aut Javier Sáez-Valero verfasserin aut Jorge Fuentealba verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 142(2021), Seite 111968- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:142 year:2021 pages:111968- https://doi.org/10.1016/j.biopha.2021.111968 kostenfrei https://doaj.org/article/f03fd7d2d1614c0494836fa2ce159013 kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332221007502 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 142 2021 111968-
allfieldsGer	10.1016/j.biopha.2021.111968 doi (DE-627)DOAJ001164902 (DE-599)DOAJf03fd7d2d1614c0494836fa2ce159013 DE-627 ger DE-627 rakwb eng RM1-950 Pamela A. Godoy verfasserin aut Increased P2×2 receptors induced by amyloid-β peptide participates in the neurotoxicity in alzheimer’s disease 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Amyloid beta peptide (Aβ) is tightly associated with the physiopathology of Alzheimer’s Disease (AD) as one of the most important factors in the evolution of the pathology. In this context, we previously reported that Aβ increases the expression of ionotropic purinergic receptor 2 (P2×2R). However, its role on the cellular and molecular Aβ toxicity is unknown, especially in human brain of AD patients. Using cellular and molecular approaches in hippocampal neurons, PC12 cells, and human brain samples of patients with AD, we evaluated the participation of P2×2R in the physiopathology of AD. Here, we reported that Aβ oligomers (Aβo) increased P2×2 levels in mice hippocampal neurons, and that this receptor increases at late Braak stages of AD patients. Aβo also increases the colocalization of APP with Rab5, an early endosomes marker, and decreased the nuclear/cytoplasmic ratio of Fe65 and PGC-1α immunoreactivity. The overexpression in PC12 cells of P2×2a, but not P2×2b, replicated these changes in Fe65 and PGC-1α; however, both overexpressed isoforms increased levels of Aβ. Taken together, these data suggest that P2×2 is upregulated in AD and it could be a key potentiator of the physiopathology of Aβ. Our results point to a possible participation in a toxic cycle that increases Aβ production, Ca2+ overload, and a decrease of PGC-1α. These novel findings put the P2×2R as a key novel pharmacological target to develop new therapeutic strategies to treat Alzheimer’s Disease. P2×2 Purinergic receptors Amyloid beta Alzheimer’s disease Fe65 APP Therapeutics. Pharmacology Daniela Mennickent verfasserin aut Inmaculada Cuchillo-Ibáñez verfasserin aut Oscar Ramírez-Molina verfasserin aut Tiare Silva-Grecchi verfasserin aut Jessica Panes-Fernández verfasserin aut Patricio Castro verfasserin aut Javier Sáez-Valero verfasserin aut Jorge Fuentealba verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 142(2021), Seite 111968- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:142 year:2021 pages:111968- https://doi.org/10.1016/j.biopha.2021.111968 kostenfrei https://doaj.org/article/f03fd7d2d1614c0494836fa2ce159013 kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332221007502 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 142 2021 111968-
allfieldsSound	10.1016/j.biopha.2021.111968 doi (DE-627)DOAJ001164902 (DE-599)DOAJf03fd7d2d1614c0494836fa2ce159013 DE-627 ger DE-627 rakwb eng RM1-950 Pamela A. Godoy verfasserin aut Increased P2×2 receptors induced by amyloid-β peptide participates in the neurotoxicity in alzheimer’s disease 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Amyloid beta peptide (Aβ) is tightly associated with the physiopathology of Alzheimer’s Disease (AD) as one of the most important factors in the evolution of the pathology. In this context, we previously reported that Aβ increases the expression of ionotropic purinergic receptor 2 (P2×2R). However, its role on the cellular and molecular Aβ toxicity is unknown, especially in human brain of AD patients. Using cellular and molecular approaches in hippocampal neurons, PC12 cells, and human brain samples of patients with AD, we evaluated the participation of P2×2R in the physiopathology of AD. Here, we reported that Aβ oligomers (Aβo) increased P2×2 levels in mice hippocampal neurons, and that this receptor increases at late Braak stages of AD patients. Aβo also increases the colocalization of APP with Rab5, an early endosomes marker, and decreased the nuclear/cytoplasmic ratio of Fe65 and PGC-1α immunoreactivity. The overexpression in PC12 cells of P2×2a, but not P2×2b, replicated these changes in Fe65 and PGC-1α; however, both overexpressed isoforms increased levels of Aβ. Taken together, these data suggest that P2×2 is upregulated in AD and it could be a key potentiator of the physiopathology of Aβ. Our results point to a possible participation in a toxic cycle that increases Aβ production, Ca2+ overload, and a decrease of PGC-1α. These novel findings put the P2×2R as a key novel pharmacological target to develop new therapeutic strategies to treat Alzheimer’s Disease. P2×2 Purinergic receptors Amyloid beta Alzheimer’s disease Fe65 APP Therapeutics. Pharmacology Daniela Mennickent verfasserin aut Inmaculada Cuchillo-Ibáñez verfasserin aut Oscar Ramírez-Molina verfasserin aut Tiare Silva-Grecchi verfasserin aut Jessica Panes-Fernández verfasserin aut Patricio Castro verfasserin aut Javier Sáez-Valero verfasserin aut Jorge Fuentealba verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 142(2021), Seite 111968- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:142 year:2021 pages:111968- https://doi.org/10.1016/j.biopha.2021.111968 kostenfrei https://doaj.org/article/f03fd7d2d1614c0494836fa2ce159013 kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332221007502 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 142 2021 111968-
language	English
source	In Biomedicine & Pharmacotherapy 142(2021), Seite 111968- volume:142 year:2021 pages:111968-
sourceStr	In Biomedicine & Pharmacotherapy 142(2021), Seite 111968- volume:142 year:2021 pages:111968-
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	P2×2 Purinergic receptors Amyloid beta Alzheimer’s disease Fe65 APP Therapeutics. Pharmacology
isfreeaccess_bool	true
container_title	Biomedicine & Pharmacotherapy
authorswithroles_txt_mv	Pamela A. Godoy @@aut@@ Daniela Mennickent @@aut@@ Inmaculada Cuchillo-Ibáñez @@aut@@ Oscar Ramírez-Molina @@aut@@ Tiare Silva-Grecchi @@aut@@ Jessica Panes-Fernández @@aut@@ Patricio Castro @@aut@@ Javier Sáez-Valero @@aut@@ Jorge Fuentealba @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	306717565
id	DOAJ001164902
language_de	englisch
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callnumber-first	R - Medicine
author	Pamela A. Godoy
spellingShingle	Pamela A. Godoy misc RM1-950 misc P2×2 misc Purinergic receptors misc Amyloid beta misc Alzheimer’s disease misc Fe65 misc APP misc Therapeutics. Pharmacology Increased P2×2 receptors induced by amyloid-β peptide participates in the neurotoxicity in alzheimer’s disease
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topic_title	RM1-950 Increased P2×2 receptors induced by amyloid-β peptide participates in the neurotoxicity in alzheimer’s disease P2×2 Purinergic receptors Amyloid beta Alzheimer’s disease Fe65 APP
topic	misc RM1-950 misc P2×2 misc Purinergic receptors misc Amyloid beta misc Alzheimer’s disease misc Fe65 misc APP misc Therapeutics. Pharmacology
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title	Increased P2×2 receptors induced by amyloid-β peptide participates in the neurotoxicity in alzheimer’s disease
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title_full	Increased P2×2 receptors induced by amyloid-β peptide participates in the neurotoxicity in alzheimer’s disease
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author_browse	Pamela A. Godoy Daniela Mennickent Inmaculada Cuchillo-Ibáñez Oscar Ramírez-Molina Tiare Silva-Grecchi Jessica Panes-Fernández Patricio Castro Javier Sáez-Valero Jorge Fuentealba
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title_sort	increased p2×2 receptors induced by amyloid-β peptide participates in the neurotoxicity in alzheimer’s disease
callnumber	RM1-950
title_auth	Increased P2×2 receptors induced by amyloid-β peptide participates in the neurotoxicity in alzheimer’s disease
abstract	Amyloid beta peptide (Aβ) is tightly associated with the physiopathology of Alzheimer’s Disease (AD) as one of the most important factors in the evolution of the pathology. In this context, we previously reported that Aβ increases the expression of ionotropic purinergic receptor 2 (P2×2R). However, its role on the cellular and molecular Aβ toxicity is unknown, especially in human brain of AD patients. Using cellular and molecular approaches in hippocampal neurons, PC12 cells, and human brain samples of patients with AD, we evaluated the participation of P2×2R in the physiopathology of AD. Here, we reported that Aβ oligomers (Aβo) increased P2×2 levels in mice hippocampal neurons, and that this receptor increases at late Braak stages of AD patients. Aβo also increases the colocalization of APP with Rab5, an early endosomes marker, and decreased the nuclear/cytoplasmic ratio of Fe65 and PGC-1α immunoreactivity. The overexpression in PC12 cells of P2×2a, but not P2×2b, replicated these changes in Fe65 and PGC-1α; however, both overexpressed isoforms increased levels of Aβ. Taken together, these data suggest that P2×2 is upregulated in AD and it could be a key potentiator of the physiopathology of Aβ. Our results point to a possible participation in a toxic cycle that increases Aβ production, Ca2+ overload, and a decrease of PGC-1α. These novel findings put the P2×2R as a key novel pharmacological target to develop new therapeutic strategies to treat Alzheimer’s Disease.
abstractGer	Amyloid beta peptide (Aβ) is tightly associated with the physiopathology of Alzheimer’s Disease (AD) as one of the most important factors in the evolution of the pathology. In this context, we previously reported that Aβ increases the expression of ionotropic purinergic receptor 2 (P2×2R). However, its role on the cellular and molecular Aβ toxicity is unknown, especially in human brain of AD patients. Using cellular and molecular approaches in hippocampal neurons, PC12 cells, and human brain samples of patients with AD, we evaluated the participation of P2×2R in the physiopathology of AD. Here, we reported that Aβ oligomers (Aβo) increased P2×2 levels in mice hippocampal neurons, and that this receptor increases at late Braak stages of AD patients. Aβo also increases the colocalization of APP with Rab5, an early endosomes marker, and decreased the nuclear/cytoplasmic ratio of Fe65 and PGC-1α immunoreactivity. The overexpression in PC12 cells of P2×2a, but not P2×2b, replicated these changes in Fe65 and PGC-1α; however, both overexpressed isoforms increased levels of Aβ. Taken together, these data suggest that P2×2 is upregulated in AD and it could be a key potentiator of the physiopathology of Aβ. Our results point to a possible participation in a toxic cycle that increases Aβ production, Ca2+ overload, and a decrease of PGC-1α. These novel findings put the P2×2R as a key novel pharmacological target to develop new therapeutic strategies to treat Alzheimer’s Disease.
abstract_unstemmed	Amyloid beta peptide (Aβ) is tightly associated with the physiopathology of Alzheimer’s Disease (AD) as one of the most important factors in the evolution of the pathology. In this context, we previously reported that Aβ increases the expression of ionotropic purinergic receptor 2 (P2×2R). However, its role on the cellular and molecular Aβ toxicity is unknown, especially in human brain of AD patients. Using cellular and molecular approaches in hippocampal neurons, PC12 cells, and human brain samples of patients with AD, we evaluated the participation of P2×2R in the physiopathology of AD. Here, we reported that Aβ oligomers (Aβo) increased P2×2 levels in mice hippocampal neurons, and that this receptor increases at late Braak stages of AD patients. Aβo also increases the colocalization of APP with Rab5, an early endosomes marker, and decreased the nuclear/cytoplasmic ratio of Fe65 and PGC-1α immunoreactivity. The overexpression in PC12 cells of P2×2a, but not P2×2b, replicated these changes in Fe65 and PGC-1α; however, both overexpressed isoforms increased levels of Aβ. Taken together, these data suggest that P2×2 is upregulated in AD and it could be a key potentiator of the physiopathology of Aβ. Our results point to a possible participation in a toxic cycle that increases Aβ production, Ca2+ overload, and a decrease of PGC-1α. These novel findings put the P2×2R as a key novel pharmacological target to develop new therapeutic strategies to treat Alzheimer’s Disease.
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title_short	Increased P2×2 receptors induced by amyloid-β peptide participates in the neurotoxicity in alzheimer’s disease
url	https://doi.org/10.1016/j.biopha.2021.111968 https://doaj.org/article/f03fd7d2d1614c0494836fa2ce159013 http://www.sciencedirect.com/science/article/pii/S0753332221007502 https://doaj.org/toc/0753-3322
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Increased P2×2 receptors induced by amyloid-β peptide participates in the neurotoxicity in alzheimer’s disease

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