TG2 promotes amyloid beta aggregates: Impact on ER-mitochondria crosstalk, calcium homeostasis and synaptic function in Alzheimer’s disease

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly affects the elderly. AD’s main features have been related to cellular and molecular events, including the aberrant aggregation of the amyloid beta peptide (Aβ), Ca2+ dyshomeostasis,...
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Autor*in:	Jessica Panes-Fernandez [verfasserIn] Pamela A. Godoy [verfasserIn] Javiera Gavilan [verfasserIn] Oscar Ramírez-Molina [verfasserIn] Carlos Felipe Burgos [verfasserIn] Ana Marileo [verfasserIn] Oscar Flores-Núñez [verfasserIn] Patricio A. Castro [verfasserIn] Gustavo Moraga-Cid [verfasserIn] Gonzalo E. Yévenes [verfasserIn] Carola Muñoz-Montesino [verfasserIn] Jorge Fuentealba [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Amyloid-β peptide Amyloid-β oligomers Mitochondrial function Ca2+ homeostasis transglutaminase type 2 Alzheimer disease

Übergeordnetes Werk:	In: Biomedicine & Pharmacotherapy - Elsevier, 2021, 162(2023), Seite 114596-
Übergeordnetes Werk:	volume:162 ; year:2023 ; pages:114596-

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.biopha.2023.114596

Katalog-ID:	DOAJ08894039X

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allfields	10.1016/j.biopha.2023.114596 doi (DE-627)DOAJ08894039X (DE-599)DOAJba5b45244eaa451799f6f3c53f3d411c DE-627 ger DE-627 rakwb eng RM1-950 Jessica Panes-Fernandez verfasserin aut TG2 promotes amyloid beta aggregates: Impact on ER-mitochondria crosstalk, calcium homeostasis and synaptic function in Alzheimer’s disease 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly affects the elderly. AD’s main features have been related to cellular and molecular events, including the aberrant aggregation of the amyloid beta peptide (Aβ), Ca2+ dyshomeostasis, and increased mitochondria-associated membranes (MAMs). Transglutaminase type 2 (TG2) is a ubiquitous enzyme whose primary role is the Ca2+-dependent proteins transamidation, including the Aβ peptide. TG2 activity has been closely related to cellular damage and death. We detected increased TG2 levels in neuronal cells treated with Aβ oligomers (AβOs) and hippocampal slices from J20 mice using cellular and molecular approaches. In this work, we characterized the capacity of TG2 to interact and promote Aβ toxic aggregates (AβTG2). AβTG2 induced an acute increase in intracellular Ca2+, miniature currents, and hiperexcitability, consistent with an increased mitochondrial Ca2+ overload, IP3R-VDAC tethering, and mitochondria-endoplasmic reticulum contacts (MERCs). AβTG2 also decreased neuronal viability and excitatory postsynaptic currents, reinforcing the idea of synaptic failure associated with MAMs dysregulation mediated by TG2. Z-DON treatment, TG2 inhibitor, reduced calcium overload, mitochondrial membrane potential loss, and synaptic failure, indicating an involvement of TG2 in a toxic cycle which increases Aβ aggregation, Ca2+ overload, and MAMs upregulation. These data provide novel information regarding the role TG2 plays in synaptic function and contribute additional evidence to support the further development of TG2 inhibitors as a disease-modifying strategy for AD. Amyloid-β peptide Amyloid-β oligomers Mitochondrial function Ca2+ homeostasis transglutaminase type 2 Alzheimer disease Therapeutics. Pharmacology Pamela A. Godoy verfasserin aut Javiera Gavilan verfasserin aut Oscar Ramírez-Molina verfasserin aut Carlos Felipe Burgos verfasserin aut Ana Marileo verfasserin aut Oscar Flores-Núñez verfasserin aut Patricio A. Castro verfasserin aut Gustavo Moraga-Cid verfasserin aut Gonzalo E. Yévenes verfasserin aut Carola Muñoz-Montesino verfasserin aut Jorge Fuentealba verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 162(2023), Seite 114596- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:162 year:2023 pages:114596- https://doi.org/10.1016/j.biopha.2023.114596 kostenfrei https://doaj.org/article/ba5b45244eaa451799f6f3c53f3d411c kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332223003840 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_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 162 2023 114596-
spelling	10.1016/j.biopha.2023.114596 doi (DE-627)DOAJ08894039X (DE-599)DOAJba5b45244eaa451799f6f3c53f3d411c DE-627 ger DE-627 rakwb eng RM1-950 Jessica Panes-Fernandez verfasserin aut TG2 promotes amyloid beta aggregates: Impact on ER-mitochondria crosstalk, calcium homeostasis and synaptic function in Alzheimer’s disease 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly affects the elderly. AD’s main features have been related to cellular and molecular events, including the aberrant aggregation of the amyloid beta peptide (Aβ), Ca2+ dyshomeostasis, and increased mitochondria-associated membranes (MAMs). Transglutaminase type 2 (TG2) is a ubiquitous enzyme whose primary role is the Ca2+-dependent proteins transamidation, including the Aβ peptide. TG2 activity has been closely related to cellular damage and death. We detected increased TG2 levels in neuronal cells treated with Aβ oligomers (AβOs) and hippocampal slices from J20 mice using cellular and molecular approaches. In this work, we characterized the capacity of TG2 to interact and promote Aβ toxic aggregates (AβTG2). AβTG2 induced an acute increase in intracellular Ca2+, miniature currents, and hiperexcitability, consistent with an increased mitochondrial Ca2+ overload, IP3R-VDAC tethering, and mitochondria-endoplasmic reticulum contacts (MERCs). AβTG2 also decreased neuronal viability and excitatory postsynaptic currents, reinforcing the idea of synaptic failure associated with MAMs dysregulation mediated by TG2. Z-DON treatment, TG2 inhibitor, reduced calcium overload, mitochondrial membrane potential loss, and synaptic failure, indicating an involvement of TG2 in a toxic cycle which increases Aβ aggregation, Ca2+ overload, and MAMs upregulation. These data provide novel information regarding the role TG2 plays in synaptic function and contribute additional evidence to support the further development of TG2 inhibitors as a disease-modifying strategy for AD. Amyloid-β peptide Amyloid-β oligomers Mitochondrial function Ca2+ homeostasis transglutaminase type 2 Alzheimer disease Therapeutics. Pharmacology Pamela A. Godoy verfasserin aut Javiera Gavilan verfasserin aut Oscar Ramírez-Molina verfasserin aut Carlos Felipe Burgos verfasserin aut Ana Marileo verfasserin aut Oscar Flores-Núñez verfasserin aut Patricio A. Castro verfasserin aut Gustavo Moraga-Cid verfasserin aut Gonzalo E. Yévenes verfasserin aut Carola Muñoz-Montesino verfasserin aut Jorge Fuentealba verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 162(2023), Seite 114596- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:162 year:2023 pages:114596- https://doi.org/10.1016/j.biopha.2023.114596 kostenfrei https://doaj.org/article/ba5b45244eaa451799f6f3c53f3d411c kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332223003840 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_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 162 2023 114596-
allfields_unstemmed	10.1016/j.biopha.2023.114596 doi (DE-627)DOAJ08894039X (DE-599)DOAJba5b45244eaa451799f6f3c53f3d411c DE-627 ger DE-627 rakwb eng RM1-950 Jessica Panes-Fernandez verfasserin aut TG2 promotes amyloid beta aggregates: Impact on ER-mitochondria crosstalk, calcium homeostasis and synaptic function in Alzheimer’s disease 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly affects the elderly. AD’s main features have been related to cellular and molecular events, including the aberrant aggregation of the amyloid beta peptide (Aβ), Ca2+ dyshomeostasis, and increased mitochondria-associated membranes (MAMs). Transglutaminase type 2 (TG2) is a ubiquitous enzyme whose primary role is the Ca2+-dependent proteins transamidation, including the Aβ peptide. TG2 activity has been closely related to cellular damage and death. We detected increased TG2 levels in neuronal cells treated with Aβ oligomers (AβOs) and hippocampal slices from J20 mice using cellular and molecular approaches. In this work, we characterized the capacity of TG2 to interact and promote Aβ toxic aggregates (AβTG2). AβTG2 induced an acute increase in intracellular Ca2+, miniature currents, and hiperexcitability, consistent with an increased mitochondrial Ca2+ overload, IP3R-VDAC tethering, and mitochondria-endoplasmic reticulum contacts (MERCs). AβTG2 also decreased neuronal viability and excitatory postsynaptic currents, reinforcing the idea of synaptic failure associated with MAMs dysregulation mediated by TG2. Z-DON treatment, TG2 inhibitor, reduced calcium overload, mitochondrial membrane potential loss, and synaptic failure, indicating an involvement of TG2 in a toxic cycle which increases Aβ aggregation, Ca2+ overload, and MAMs upregulation. These data provide novel information regarding the role TG2 plays in synaptic function and contribute additional evidence to support the further development of TG2 inhibitors as a disease-modifying strategy for AD. Amyloid-β peptide Amyloid-β oligomers Mitochondrial function Ca2+ homeostasis transglutaminase type 2 Alzheimer disease Therapeutics. Pharmacology Pamela A. Godoy verfasserin aut Javiera Gavilan verfasserin aut Oscar Ramírez-Molina verfasserin aut Carlos Felipe Burgos verfasserin aut Ana Marileo verfasserin aut Oscar Flores-Núñez verfasserin aut Patricio A. Castro verfasserin aut Gustavo Moraga-Cid verfasserin aut Gonzalo E. Yévenes verfasserin aut Carola Muñoz-Montesino verfasserin aut Jorge Fuentealba verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 162(2023), Seite 114596- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:162 year:2023 pages:114596- https://doi.org/10.1016/j.biopha.2023.114596 kostenfrei https://doaj.org/article/ba5b45244eaa451799f6f3c53f3d411c kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332223003840 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_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 162 2023 114596-
allfieldsGer	10.1016/j.biopha.2023.114596 doi (DE-627)DOAJ08894039X (DE-599)DOAJba5b45244eaa451799f6f3c53f3d411c DE-627 ger DE-627 rakwb eng RM1-950 Jessica Panes-Fernandez verfasserin aut TG2 promotes amyloid beta aggregates: Impact on ER-mitochondria crosstalk, calcium homeostasis and synaptic function in Alzheimer’s disease 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly affects the elderly. AD’s main features have been related to cellular and molecular events, including the aberrant aggregation of the amyloid beta peptide (Aβ), Ca2+ dyshomeostasis, and increased mitochondria-associated membranes (MAMs). Transglutaminase type 2 (TG2) is a ubiquitous enzyme whose primary role is the Ca2+-dependent proteins transamidation, including the Aβ peptide. TG2 activity has been closely related to cellular damage and death. We detected increased TG2 levels in neuronal cells treated with Aβ oligomers (AβOs) and hippocampal slices from J20 mice using cellular and molecular approaches. In this work, we characterized the capacity of TG2 to interact and promote Aβ toxic aggregates (AβTG2). AβTG2 induced an acute increase in intracellular Ca2+, miniature currents, and hiperexcitability, consistent with an increased mitochondrial Ca2+ overload, IP3R-VDAC tethering, and mitochondria-endoplasmic reticulum contacts (MERCs). AβTG2 also decreased neuronal viability and excitatory postsynaptic currents, reinforcing the idea of synaptic failure associated with MAMs dysregulation mediated by TG2. Z-DON treatment, TG2 inhibitor, reduced calcium overload, mitochondrial membrane potential loss, and synaptic failure, indicating an involvement of TG2 in a toxic cycle which increases Aβ aggregation, Ca2+ overload, and MAMs upregulation. These data provide novel information regarding the role TG2 plays in synaptic function and contribute additional evidence to support the further development of TG2 inhibitors as a disease-modifying strategy for AD. Amyloid-β peptide Amyloid-β oligomers Mitochondrial function Ca2+ homeostasis transglutaminase type 2 Alzheimer disease Therapeutics. Pharmacology Pamela A. Godoy verfasserin aut Javiera Gavilan verfasserin aut Oscar Ramírez-Molina verfasserin aut Carlos Felipe Burgos verfasserin aut Ana Marileo verfasserin aut Oscar Flores-Núñez verfasserin aut Patricio A. Castro verfasserin aut Gustavo Moraga-Cid verfasserin aut Gonzalo E. Yévenes verfasserin aut Carola Muñoz-Montesino verfasserin aut Jorge Fuentealba verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 162(2023), Seite 114596- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:162 year:2023 pages:114596- https://doi.org/10.1016/j.biopha.2023.114596 kostenfrei https://doaj.org/article/ba5b45244eaa451799f6f3c53f3d411c kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332223003840 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_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 162 2023 114596-
allfieldsSound	10.1016/j.biopha.2023.114596 doi (DE-627)DOAJ08894039X (DE-599)DOAJba5b45244eaa451799f6f3c53f3d411c DE-627 ger DE-627 rakwb eng RM1-950 Jessica Panes-Fernandez verfasserin aut TG2 promotes amyloid beta aggregates: Impact on ER-mitochondria crosstalk, calcium homeostasis and synaptic function in Alzheimer’s disease 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly affects the elderly. AD’s main features have been related to cellular and molecular events, including the aberrant aggregation of the amyloid beta peptide (Aβ), Ca2+ dyshomeostasis, and increased mitochondria-associated membranes (MAMs). Transglutaminase type 2 (TG2) is a ubiquitous enzyme whose primary role is the Ca2+-dependent proteins transamidation, including the Aβ peptide. TG2 activity has been closely related to cellular damage and death. We detected increased TG2 levels in neuronal cells treated with Aβ oligomers (AβOs) and hippocampal slices from J20 mice using cellular and molecular approaches. In this work, we characterized the capacity of TG2 to interact and promote Aβ toxic aggregates (AβTG2). AβTG2 induced an acute increase in intracellular Ca2+, miniature currents, and hiperexcitability, consistent with an increased mitochondrial Ca2+ overload, IP3R-VDAC tethering, and mitochondria-endoplasmic reticulum contacts (MERCs). AβTG2 also decreased neuronal viability and excitatory postsynaptic currents, reinforcing the idea of synaptic failure associated with MAMs dysregulation mediated by TG2. Z-DON treatment, TG2 inhibitor, reduced calcium overload, mitochondrial membrane potential loss, and synaptic failure, indicating an involvement of TG2 in a toxic cycle which increases Aβ aggregation, Ca2+ overload, and MAMs upregulation. These data provide novel information regarding the role TG2 plays in synaptic function and contribute additional evidence to support the further development of TG2 inhibitors as a disease-modifying strategy for AD. Amyloid-β peptide Amyloid-β oligomers Mitochondrial function Ca2+ homeostasis transglutaminase type 2 Alzheimer disease Therapeutics. Pharmacology Pamela A. Godoy verfasserin aut Javiera Gavilan verfasserin aut Oscar Ramírez-Molina verfasserin aut Carlos Felipe Burgos verfasserin aut Ana Marileo verfasserin aut Oscar Flores-Núñez verfasserin aut Patricio A. Castro verfasserin aut Gustavo Moraga-Cid verfasserin aut Gonzalo E. Yévenes verfasserin aut Carola Muñoz-Montesino verfasserin aut Jorge Fuentealba verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 162(2023), Seite 114596- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:162 year:2023 pages:114596- https://doi.org/10.1016/j.biopha.2023.114596 kostenfrei https://doaj.org/article/ba5b45244eaa451799f6f3c53f3d411c kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332223003840 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_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 162 2023 114596-
language	English
source	In Biomedicine & Pharmacotherapy 162(2023), Seite 114596- volume:162 year:2023 pages:114596-
sourceStr	In Biomedicine & Pharmacotherapy 162(2023), Seite 114596- volume:162 year:2023 pages:114596-
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Amyloid-β peptide Amyloid-β oligomers Mitochondrial function Ca2+ homeostasis transglutaminase type 2 Alzheimer disease Therapeutics. Pharmacology
isfreeaccess_bool	true
container_title	Biomedicine & Pharmacotherapy
authorswithroles_txt_mv	Jessica Panes-Fernandez @@aut@@ Pamela A. Godoy @@aut@@ Javiera Gavilan @@aut@@ Oscar Ramírez-Molina @@aut@@ Carlos Felipe Burgos @@aut@@ Ana Marileo @@aut@@ Oscar Flores-Núñez @@aut@@ Patricio A. Castro @@aut@@ Gustavo Moraga-Cid @@aut@@ Gonzalo E. Yévenes @@aut@@ Carola Muñoz-Montesino @@aut@@ Jorge Fuentealba @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	306717565
id	DOAJ08894039X
language_de	englisch
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callnumber-first	R - Medicine
author	Jessica Panes-Fernandez
spellingShingle	Jessica Panes-Fernandez misc RM1-950 misc Amyloid-β peptide misc Amyloid-β oligomers misc Mitochondrial function misc Ca2+ homeostasis misc transglutaminase type 2 misc Alzheimer disease misc Therapeutics. Pharmacology TG2 promotes amyloid beta aggregates: Impact on ER-mitochondria crosstalk, calcium homeostasis and synaptic function in Alzheimer’s disease
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topic_title	RM1-950 TG2 promotes amyloid beta aggregates: Impact on ER-mitochondria crosstalk, calcium homeostasis and synaptic function in Alzheimer’s disease Amyloid-β peptide Amyloid-β oligomers Mitochondrial function Ca2+ homeostasis transglutaminase type 2 Alzheimer disease
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title	TG2 promotes amyloid beta aggregates: Impact on ER-mitochondria crosstalk, calcium homeostasis and synaptic function in Alzheimer’s disease
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title_full	TG2 promotes amyloid beta aggregates: Impact on ER-mitochondria crosstalk, calcium homeostasis and synaptic function in Alzheimer’s disease
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author_browse	Jessica Panes-Fernandez Pamela A. Godoy Javiera Gavilan Oscar Ramírez-Molina Carlos Felipe Burgos Ana Marileo Oscar Flores-Núñez Patricio A. Castro Gustavo Moraga-Cid Gonzalo E. Yévenes Carola Muñoz-Montesino Jorge Fuentealba
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title_sort	tg2 promotes amyloid beta aggregates: impact on er-mitochondria crosstalk, calcium homeostasis and synaptic function in alzheimer’s disease
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title_auth	TG2 promotes amyloid beta aggregates: Impact on ER-mitochondria crosstalk, calcium homeostasis and synaptic function in Alzheimer’s disease
abstract	Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly affects the elderly. AD’s main features have been related to cellular and molecular events, including the aberrant aggregation of the amyloid beta peptide (Aβ), Ca2+ dyshomeostasis, and increased mitochondria-associated membranes (MAMs). Transglutaminase type 2 (TG2) is a ubiquitous enzyme whose primary role is the Ca2+-dependent proteins transamidation, including the Aβ peptide. TG2 activity has been closely related to cellular damage and death. We detected increased TG2 levels in neuronal cells treated with Aβ oligomers (AβOs) and hippocampal slices from J20 mice using cellular and molecular approaches. In this work, we characterized the capacity of TG2 to interact and promote Aβ toxic aggregates (AβTG2). AβTG2 induced an acute increase in intracellular Ca2+, miniature currents, and hiperexcitability, consistent with an increased mitochondrial Ca2+ overload, IP3R-VDAC tethering, and mitochondria-endoplasmic reticulum contacts (MERCs). AβTG2 also decreased neuronal viability and excitatory postsynaptic currents, reinforcing the idea of synaptic failure associated with MAMs dysregulation mediated by TG2. Z-DON treatment, TG2 inhibitor, reduced calcium overload, mitochondrial membrane potential loss, and synaptic failure, indicating an involvement of TG2 in a toxic cycle which increases Aβ aggregation, Ca2+ overload, and MAMs upregulation. These data provide novel information regarding the role TG2 plays in synaptic function and contribute additional evidence to support the further development of TG2 inhibitors as a disease-modifying strategy for AD.
abstractGer	Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly affects the elderly. AD’s main features have been related to cellular and molecular events, including the aberrant aggregation of the amyloid beta peptide (Aβ), Ca2+ dyshomeostasis, and increased mitochondria-associated membranes (MAMs). Transglutaminase type 2 (TG2) is a ubiquitous enzyme whose primary role is the Ca2+-dependent proteins transamidation, including the Aβ peptide. TG2 activity has been closely related to cellular damage and death. We detected increased TG2 levels in neuronal cells treated with Aβ oligomers (AβOs) and hippocampal slices from J20 mice using cellular and molecular approaches. In this work, we characterized the capacity of TG2 to interact and promote Aβ toxic aggregates (AβTG2). AβTG2 induced an acute increase in intracellular Ca2+, miniature currents, and hiperexcitability, consistent with an increased mitochondrial Ca2+ overload, IP3R-VDAC tethering, and mitochondria-endoplasmic reticulum contacts (MERCs). AβTG2 also decreased neuronal viability and excitatory postsynaptic currents, reinforcing the idea of synaptic failure associated with MAMs dysregulation mediated by TG2. Z-DON treatment, TG2 inhibitor, reduced calcium overload, mitochondrial membrane potential loss, and synaptic failure, indicating an involvement of TG2 in a toxic cycle which increases Aβ aggregation, Ca2+ overload, and MAMs upregulation. These data provide novel information regarding the role TG2 plays in synaptic function and contribute additional evidence to support the further development of TG2 inhibitors as a disease-modifying strategy for AD.
abstract_unstemmed	Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly affects the elderly. AD’s main features have been related to cellular and molecular events, including the aberrant aggregation of the amyloid beta peptide (Aβ), Ca2+ dyshomeostasis, and increased mitochondria-associated membranes (MAMs). Transglutaminase type 2 (TG2) is a ubiquitous enzyme whose primary role is the Ca2+-dependent proteins transamidation, including the Aβ peptide. TG2 activity has been closely related to cellular damage and death. We detected increased TG2 levels in neuronal cells treated with Aβ oligomers (AβOs) and hippocampal slices from J20 mice using cellular and molecular approaches. In this work, we characterized the capacity of TG2 to interact and promote Aβ toxic aggregates (AβTG2). AβTG2 induced an acute increase in intracellular Ca2+, miniature currents, and hiperexcitability, consistent with an increased mitochondrial Ca2+ overload, IP3R-VDAC tethering, and mitochondria-endoplasmic reticulum contacts (MERCs). AβTG2 also decreased neuronal viability and excitatory postsynaptic currents, reinforcing the idea of synaptic failure associated with MAMs dysregulation mediated by TG2. Z-DON treatment, TG2 inhibitor, reduced calcium overload, mitochondrial membrane potential loss, and synaptic failure, indicating an involvement of TG2 in a toxic cycle which increases Aβ aggregation, Ca2+ overload, and MAMs upregulation. These data provide novel information regarding the role TG2 plays in synaptic function and contribute additional evidence to support the further development of TG2 inhibitors as a disease-modifying strategy for AD.
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title_short	TG2 promotes amyloid beta aggregates: Impact on ER-mitochondria crosstalk, calcium homeostasis and synaptic function in Alzheimer’s disease
url	https://doi.org/10.1016/j.biopha.2023.114596 https://doaj.org/article/ba5b45244eaa451799f6f3c53f3d411c http://www.sciencedirect.com/science/article/pii/S0753332223003840 https://doaj.org/toc/0753-3322
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