Tau deletion promotes brain insulin resistance
<p dir="ltr">The molecular pathways underlying tau pathology–induced synaptic/cognitive deficits and neurodegeneration are poorly understood. One prevalent hypothesis is that hyperphosphorylation, misfolding, and fibrillization of tau impair synaptic plasticity and cause degeneration...
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2017
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| _version_ | 1864513556576206848 |
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| author | Elodie Marciniak (18892114) |
| author2 | Antoine Leboucher (7454165) Emilie Caron (11899199) Tariq Ahmed (5768081) Anne Tailleux (330488) Julie Dumont (224385) Tarik Issad (149334) Ellen Gerhardt (185546) Patrick Pagesy (149321) Margaux Vileno (18892117) Clément Bournonville (18892120) Malika Hamdane (373776) Kadiombo Bantubungi (330472) Steve Lancel (146004) Dominique Demeyer (75873) Sabiha Eddarkaoui (1618621) Emmanuelle Vallez (4006400) Didier Vieau (122216) Sandrine Humez (18892123) Emilie Faivre (5507582) Benjamin Grenier-Boley (577027) Tiago F. Outeiro (191379) Bart Staels (15303) Philippe Amouyel (161598) Detlef Balschun (8096618) Luc Buee (16270421) David Blum (344593) |
| author2_role | author author author author author author author author author author author author author author author author author author author author author author author author author author |
| author_facet | Elodie Marciniak (18892114) Antoine Leboucher (7454165) Emilie Caron (11899199) Tariq Ahmed (5768081) Anne Tailleux (330488) Julie Dumont (224385) Tarik Issad (149334) Ellen Gerhardt (185546) Patrick Pagesy (149321) Margaux Vileno (18892117) Clément Bournonville (18892120) Malika Hamdane (373776) Kadiombo Bantubungi (330472) Steve Lancel (146004) Dominique Demeyer (75873) Sabiha Eddarkaoui (1618621) Emmanuelle Vallez (4006400) Didier Vieau (122216) Sandrine Humez (18892123) Emilie Faivre (5507582) Benjamin Grenier-Boley (577027) Tiago F. Outeiro (191379) Bart Staels (15303) Philippe Amouyel (161598) Detlef Balschun (8096618) Luc Buee (16270421) David Blum (344593) |
| author_role | author |
| dc.creator.none.fl_str_mv | Elodie Marciniak (18892114) Antoine Leboucher (7454165) Emilie Caron (11899199) Tariq Ahmed (5768081) Anne Tailleux (330488) Julie Dumont (224385) Tarik Issad (149334) Ellen Gerhardt (185546) Patrick Pagesy (149321) Margaux Vileno (18892117) Clément Bournonville (18892120) Malika Hamdane (373776) Kadiombo Bantubungi (330472) Steve Lancel (146004) Dominique Demeyer (75873) Sabiha Eddarkaoui (1618621) Emmanuelle Vallez (4006400) Didier Vieau (122216) Sandrine Humez (18892123) Emilie Faivre (5507582) Benjamin Grenier-Boley (577027) Tiago F. Outeiro (191379) Bart Staels (15303) Philippe Amouyel (161598) Detlef Balschun (8096618) Luc Buee (16270421) David Blum (344593) |
| dc.date.none.fl_str_mv | 2017-06-26T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1084/jem.20161731 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Tau_deletion_promotes_brain_insulin_resistance/27088033 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Neurosciences Tau pathology Synaptic plasticity Hyperphosphorylation Insulin signaling Cognitive deficits Neurodegeneration Alzheimer's disease |
| dc.title.none.fl_str_mv | Tau deletion promotes brain insulin resistance |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">The molecular pathways underlying tau pathology–induced synaptic/cognitive deficits and neurodegeneration are poorly understood. One prevalent hypothesis is that hyperphosphorylation, misfolding, and fibrillization of tau impair synaptic plasticity and cause degeneration. However, tau pathology may also result in the loss of specific physiological tau functions, which are largely unknown but could contribute to neuronal dysfunction. In the present study, we uncovered a novel function of tau in its ability to regulate brain insulin signaling. We found that tau deletion leads to an impaired hippocampal response to insulin, caused by altered IRS-1 and PTEN (phosphatase and tensin homologue on chromosome 10) activities. Our data also demonstrate that tau knockout mice exhibit an impaired hypothalamic anorexigenic effect of insulin that is associated with energy metabolism alterations. Consistently, we found that tau haplotypes are associated with glycemic traits in humans. The present data have far-reaching clinical implications and raise the hypothesis that pathophysiological tau loss-of-function favors brain insulin resistance, which is instrumental for cognitive and metabolic impairments in Alzheimer’s disease patients.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Experimental Medicine<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1084/jem.20161731" target="_blank">https://dx.doi.org/10.1084/jem.20161731</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_009b8c3615c420b32bf0221ca84e1963 |
| identifier_str_mv | 10.1084/jem.20161731 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/27088033 |
| publishDate | 2017 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Tau deletion promotes brain insulin resistanceElodie Marciniak (18892114)Antoine Leboucher (7454165)Emilie Caron (11899199)Tariq Ahmed (5768081)Anne Tailleux (330488)Julie Dumont (224385)Tarik Issad (149334)Ellen Gerhardt (185546)Patrick Pagesy (149321)Margaux Vileno (18892117)Clément Bournonville (18892120)Malika Hamdane (373776)Kadiombo Bantubungi (330472)Steve Lancel (146004)Dominique Demeyer (75873)Sabiha Eddarkaoui (1618621)Emmanuelle Vallez (4006400)Didier Vieau (122216)Sandrine Humez (18892123)Emilie Faivre (5507582)Benjamin Grenier-Boley (577027)Tiago F. Outeiro (191379)Bart Staels (15303)Philippe Amouyel (161598)Detlef Balschun (8096618)Luc Buee (16270421)David Blum (344593)Biomedical and clinical sciencesNeurosciencesTau pathologySynaptic plasticityHyperphosphorylationInsulin signalingCognitive deficitsNeurodegenerationAlzheimer's disease<p dir="ltr">The molecular pathways underlying tau pathology–induced synaptic/cognitive deficits and neurodegeneration are poorly understood. One prevalent hypothesis is that hyperphosphorylation, misfolding, and fibrillization of tau impair synaptic plasticity and cause degeneration. However, tau pathology may also result in the loss of specific physiological tau functions, which are largely unknown but could contribute to neuronal dysfunction. In the present study, we uncovered a novel function of tau in its ability to regulate brain insulin signaling. We found that tau deletion leads to an impaired hippocampal response to insulin, caused by altered IRS-1 and PTEN (phosphatase and tensin homologue on chromosome 10) activities. Our data also demonstrate that tau knockout mice exhibit an impaired hypothalamic anorexigenic effect of insulin that is associated with energy metabolism alterations. Consistently, we found that tau haplotypes are associated with glycemic traits in humans. The present data have far-reaching clinical implications and raise the hypothesis that pathophysiological tau loss-of-function favors brain insulin resistance, which is instrumental for cognitive and metabolic impairments in Alzheimer’s disease patients.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Experimental Medicine<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1084/jem.20161731" target="_blank">https://dx.doi.org/10.1084/jem.20161731</a></p>2017-06-26T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1084/jem.20161731https://figshare.com/articles/journal_contribution/Tau_deletion_promotes_brain_insulin_resistance/27088033CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/270880332017-06-26T03:00:00Z |
| spellingShingle | Tau deletion promotes brain insulin resistance Elodie Marciniak (18892114) Biomedical and clinical sciences Neurosciences Tau pathology Synaptic plasticity Hyperphosphorylation Insulin signaling Cognitive deficits Neurodegeneration Alzheimer's disease |
| status_str | publishedVersion |
| title | Tau deletion promotes brain insulin resistance |
| title_full | Tau deletion promotes brain insulin resistance |
| title_fullStr | Tau deletion promotes brain insulin resistance |
| title_full_unstemmed | Tau deletion promotes brain insulin resistance |
| title_short | Tau deletion promotes brain insulin resistance |
| title_sort | Tau deletion promotes brain insulin resistance |
| topic | Biomedical and clinical sciences Neurosciences Tau pathology Synaptic plasticity Hyperphosphorylation Insulin signaling Cognitive deficits Neurodegeneration Alzheimer's disease |