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S327 phosphorylation of the presynaptic protein SEPTIN5 increases in the early stages of neurofibrillary pathology and alters the functionality of SEPTIN5

2022Artigo científico Acesso aberto
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dc.contributor.authorFerreira, Catarina B.
dc.contributor.authorMarttinen, Mikael
dc.contributor.authorCoelho, Joana E
dc.contributor.authorPaldanius, Kaisa M.A.
dc.contributor.authorTakalo, Mari
dc.contributor.authorMäkinen, Petra
dc.contributor.authorLeppänen, Luukas
dc.contributor.authorMiranda-Lourenço, Catarina
dc.contributor.authorFonseca-Gomes, João
dc.contributor.authorTanqueiro, Sara
dc.contributor.authorVaz, Sandra H.
dc.contributor.authorBelo, Rita F.
dc.contributor.authorSebastião, Ana M
dc.contributor.authorLeinonen, Ville
dc.contributor.authorSoininen, Hilkka
dc.contributor.authorPike, Ian
dc.contributor.authorHaapasalo, Annakaisa
dc.contributor.authorLopes, Luisa V.
dc.contributor.authorDe Mendonça, Alexandre
dc.contributor.authorDiógenes, Maria José
dc.contributor.authorHiltunen, Mikko
dc.date.accessioned2022-01-07T11:28:16Z
dc.date.available2022-01-07T11:28:16Z
dc.date.issued2022
dc.description© 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)pt_PT
dc.description.abstractAlzheimer's disease (AD) is the most common form of dementia, which is neuropathologically characterized by extracellular senile plaques containing amyloid-β and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. Previous studies have suggested a role for septin (SEPTIN) protein family members in AD-associated cellular processes. Here, we elucidated the potential role of presynaptic SEPTIN5 protein and its post-translational modifications in the molecular pathogenesis of AD. RNA and protein levels of SEPTIN5 showed a significant decrease in human temporal cortex in relation to the increasing degree of AD-related neurofibrillary pathology. Conversely, an increase in the phosphorylation of the functionally relevant SEPTIN5 phosphorylation site S327 was observed already in the early phases of AD-related neurofibrillary pathology, but not in the cerebrospinal fluid of individuals fulfilling the criteria for mild cognitive impairment due to AD. According to the mechanistic assessments, a link between SEPTIN5 S327 phosphorylation status and the effects of SEPTIN5 on amyloid precursor protein processing and markers of autophagy was discovered in mouse primary cortical neurons transduced with lentiviral constructs encoding wild type SEPTIN5 or SEPTIN5 phosphomutants (S327A and S327D). C57BL/6 J mice intrahippocampally injected with lentiviral wild type SEPTIN5 or phosphomutant constructs did not show changes in cognitive performance after five to six weeks from the start of injections. However, SEPTIN5 S327 phosphorylation status was linked to changes in short-term synaptic plasticity ex vivo at the CA3-CA1 synapse. Collectively, these data suggest that SEPTIN5 and its S327 phosphorylation status play a pivotal role in several cellular processes relevant for AD.pt_PT
dc.description.sponsorshipThis work was supported by the Academy of Finland (grant numbers 307866, 330178 and 315459); Sigrid Jusélius Foundation; the Strategic Neuroscience Funding of the University of Eastern Finland; Fundação para a Ciência e Tecnologia (grant numbers PD/BD/128390/2017, SFRH/BD/118238/2016, PD/BD/114441/2016, PD/BD/128091/2016, PD/BD/114337/2016, and PTDC/MED-NEU/27946/2017); Santa Casa da Misericórdia de Lisboa (grant number MB-37-2017); SynaNet (LISBOA-01-0145-FEDER-0073919 under the grant agreement no. 692340).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNeurobiol Dis. 2021 Dec 24;163:105603pt_PT
dc.identifier.doi10.1016/j.nbd.2021.105603pt_PT
dc.identifier.eissn1095-953X
dc.identifier.issn0969-9961
dc.identifier.urihttp://hdl.handle.net/10451/50735
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relation330178pt_PT
dc.relationMicrowave Clearance Measurement System for Low Pressure Turbines
dc.relationThe role of septins on synaptic function and on amyloid precursor protein processing
dc.relationRegulation of adenosine levels as a new therapeutic strategy for Rett Syndrome
dc.relationBDNF receptor cleavage:relevance for Alzheimer´s Disease pathophysiology
dc.relationModulation of BDNF effects by adenosine: a new strategy for schizophrenia treatment - Adenosinergic signaling as a new pharmacological target for schizophrenia treatment
dc.relationKyotorphin as new pharmacological therapeutic strategy for Alzheimers Disease
dc.relationBeyond Beta-Amyloid - Deciphering Early Pathogenic Changes in Alzheimer's disease
dc.relationNeurologic and Psychiatric Disorders: from synapses to networks
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/neurobiology-of-diseasept_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAPP processingpt_PT
dc.subjectAlzheimer's diseasept_PT
dc.subjectAutophagypt_PT
dc.subjectAβpt_PT
dc.subjectPost-translational modificationspt_PT
dc.subjectSEPTIN5pt_PT
dc.subjectSynaptic plasticitypt_PT
dc.titleS327 phosphorylation of the presynaptic protein SEPTIN5 increases in the early stages of neurofibrillary pathology and alters the functionality of SEPTIN5pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleMicrowave Clearance Measurement System for Low Pressure Turbines
oaire.awardTitleThe role of septins on synaptic function and on amyloid precursor protein processing
oaire.awardTitleRegulation of adenosine levels as a new therapeutic strategy for Rett Syndrome
oaire.awardTitleBDNF receptor cleavage:relevance for Alzheimer´s Disease pathophysiology
oaire.awardTitleModulation of BDNF effects by adenosine: a new strategy for schizophrenia treatment - Adenosinergic signaling as a new pharmacological target for schizophrenia treatment
oaire.awardTitleKyotorphin as new pharmacological therapeutic strategy for Alzheimers Disease
oaire.awardTitleBeyond Beta-Amyloid - Deciphering Early Pathogenic Changes in Alzheimer's disease
oaire.awardTitleNeurologic and Psychiatric Disorders: from synapses to networks
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/307866/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/PD%2FBD%2F128390%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F118238%2F2016/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F114441%2F2016/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F128091%2F2016/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F114337%2F2016/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FMED-NEU%2F27946%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/692340/EU
oaire.citation.titleNeurobiology of Diseasept_PT
oaire.citation.volume163pt_PT
oaire.fundingStreamFP7
oaire.fundingStreamOE
oaire.fundingStream3599-PPCDT
oaire.fundingStreamH2020
person.familyNameCoelho
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rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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