Lipid-dependent deposition of alpha-synuclein and Tau on neuronal Secretogranin II-positive vesicular membranes with age

Abstract This report demonstrates insoluble alpha-synuclein (aSYN)+ aggregates in human sporadic Parkinson’s disease (PD) midbrain that are linearly correlated with loss of glucocerebrosidase (GCase) activity. To identify early protein-lipid interactions that coincide with loss of lipid homeostasis,...

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Autores principales:	Oeystein R. Brekk, Alyssa Moskites, Ole Isacson, Penelope J. Hallett
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Secretogranin II (SgII) Large Dense Core Vesicles (LDCVs) Synaptic Vesicle Glycoprotein 2A (SV2A) GCase Activity Aged Mouse Brain Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2fdd8acdf766415e867f6634b8b4931d
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spelling	oai:doaj.org-article:2fdd8acdf766415e867f6634b8b4931d2021-12-02T15:08:01ZLipid-dependent deposition of alpha-synuclein and Tau on neuronal Secretogranin II-positive vesicular membranes with age10.1038/s41598-018-33474-z2045-2322https://doaj.org/article/2fdd8acdf766415e867f6634b8b4931d2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33474-zhttps://doaj.org/toc/2045-2322Abstract This report demonstrates insoluble alpha-synuclein (aSYN)+ aggregates in human sporadic Parkinson’s disease (PD) midbrain that are linearly correlated with loss of glucocerebrosidase (GCase) activity. To identify early protein-lipid interactions that coincide with loss of lipid homeostasis, an aging study was carried out in mice with age-dependent reductions in GCase function. The analysis identified aberrant lipid-association by aSYN and hyperphosphorylated Tau (pTau) in a specific subset of neurotransmitter-containing, Secretogranin II (SgII)+ large, dense-core vesicles (LDCVs) responsible for neurotransmission of dopamine and other monoamines. The lipid vesicle-accumulation was concurrent with loss of PSD-95 suggesting synaptic destabilization. aSYN overexpression in the absence of lipid deregulation did not recapitulate the abnormal association with SgII+ vesicles. These results show lipid-dependent changes occur with age in neuronal vesicular membrane compartments that accumulate lipid-stabilized aSYN and pTau.Oeystein R. BrekkAlyssa MoskitesOle IsacsonPenelope J. HallettNature PortfolioarticleSecretogranin II (SgII)Large Dense Core Vesicles (LDCVs)Synaptic Vesicle Glycoprotein 2A (SV2A)GCase ActivityAged Mouse BrainMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Secretogranin II (SgII) Large Dense Core Vesicles (LDCVs) Synaptic Vesicle Glycoprotein 2A (SV2A) GCase Activity Aged Mouse Brain Medicine R Science Q
spellingShingle	Secretogranin II (SgII) Large Dense Core Vesicles (LDCVs) Synaptic Vesicle Glycoprotein 2A (SV2A) GCase Activity Aged Mouse Brain Medicine R Science Q Oeystein R. Brekk Alyssa Moskites Ole Isacson Penelope J. Hallett Lipid-dependent deposition of alpha-synuclein and Tau on neuronal Secretogranin II-positive vesicular membranes with age
description	Abstract This report demonstrates insoluble alpha-synuclein (aSYN)+ aggregates in human sporadic Parkinson’s disease (PD) midbrain that are linearly correlated with loss of glucocerebrosidase (GCase) activity. To identify early protein-lipid interactions that coincide with loss of lipid homeostasis, an aging study was carried out in mice with age-dependent reductions in GCase function. The analysis identified aberrant lipid-association by aSYN and hyperphosphorylated Tau (pTau) in a specific subset of neurotransmitter-containing, Secretogranin II (SgII)+ large, dense-core vesicles (LDCVs) responsible for neurotransmission of dopamine and other monoamines. The lipid vesicle-accumulation was concurrent with loss of PSD-95 suggesting synaptic destabilization. aSYN overexpression in the absence of lipid deregulation did not recapitulate the abnormal association with SgII+ vesicles. These results show lipid-dependent changes occur with age in neuronal vesicular membrane compartments that accumulate lipid-stabilized aSYN and pTau.
format	article
author	Oeystein R. Brekk Alyssa Moskites Ole Isacson Penelope J. Hallett
author_facet	Oeystein R. Brekk Alyssa Moskites Ole Isacson Penelope J. Hallett
author_sort	Oeystein R. Brekk
title	Lipid-dependent deposition of alpha-synuclein and Tau on neuronal Secretogranin II-positive vesicular membranes with age
title_short	Lipid-dependent deposition of alpha-synuclein and Tau on neuronal Secretogranin II-positive vesicular membranes with age
title_full	Lipid-dependent deposition of alpha-synuclein and Tau on neuronal Secretogranin II-positive vesicular membranes with age
title_fullStr	Lipid-dependent deposition of alpha-synuclein and Tau on neuronal Secretogranin II-positive vesicular membranes with age
title_full_unstemmed	Lipid-dependent deposition of alpha-synuclein and Tau on neuronal Secretogranin II-positive vesicular membranes with age
title_sort	lipid-dependent deposition of alpha-synuclein and tau on neuronal secretogranin ii-positive vesicular membranes with age
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/2fdd8acdf766415e867f6634b8b4931d
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Lipid-dependent deposition of alpha-synuclein and Tau on neuronal Secretogranin II-positive vesicular membranes with age

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