The unfolded protein response transcription factor XBP1s ameliorates Alzheimer’s disease by improving synaptic function and proteostasis (doi:10.34691/FK2/VUWSYP)

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Part 1: Document Description
Part 2: Study Description
Part 3: Data Files Description
Part 4: Variable Description
Part 5: Other Study-Related Materials
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Document Description

Citation

Title:

The unfolded protein response transcription factor XBP1s ameliorates Alzheimer’s disease by improving synaptic function and proteostasis

Identification Number:

doi:10.34691/FK2/VUWSYP

Distributor:

Repositorio de datos de investigación de la Universidad de Chile

Date of Distribution:

2021-12-30

Version:

2

Bibliographic Citation:

Hetz, Claudio; Duran-Aniotz, Claudia; Rivera-Krstulovic, Catalina; Poblete, Natalia; Ardiles, Alvaro O.; Sabusap, Carleen; Gerakis, Yannis; Cabral Miranda, Felipe; Diaz, Javier; Fuentealba, Matias; Muño, Ernesto; Espinosa, Sandra; Martinez, Gabriela; Quiroz, Gabriel; Tamburini, Giovanni; Medinas, Danilo B.; Contreras, Darwin; Piña, Ricardo; Lourenci, Mychael; Figueiredo, Claudia; Ferreira, Sergio; Rozas, Carlos; Morales, Bernardo; Plate, Lars; Gonzalez-Billault, Christian; Palacios, Adrian, 2021, "The unfolded protein response transcription factor XBP1s ameliorates Alzheimer’s disease by improving synaptic function and proteostasis", https://doi.org/10.34691/FK2/VUWSYP, Repositorio de datos de investigación de la Universidad de Chile, V2, UNF:6:SCI3Lz4cZaT9RodbHbGDFg== [fileUNF]

Study Description

Citation

Title:

The unfolded protein response transcription factor XBP1s ameliorates Alzheimer’s disease by improving synaptic function and proteostasis

Identification Number:

doi:10.34691/FK2/VUWSYP

Authoring Entity:

Hetz, Claudio (Universidad de Chile)

Duran-Aniotz, Claudia (Universidad de Chile)

Rivera-Krstulovic, Catalina (Universidad de Chile)

Poblete, Natalia (Universidad de Chile)

Ardiles, Alvaro O. (Universidad de Chile)

Sabusap, Carleen (Universidad de Chile)

Gerakis, Yannis (Universidad de Chile)

Cabral Miranda, Felipe (Universidad de Chile)

Diaz, Javier (Universidad de Chile)

Fuentealba, Matias (Universidad de Chile)

Muño, Ernesto (Universidad de Chile)

Espinosa, Sandra (Universidad de Chile)

Martinez, Gabriela (Universidad de Chile)

Quiroz, Gabriel (Universidad de Chile)

Tamburini, Giovanni (Universidad de Chile)

Medinas, Danilo B. (Universidad de Chile)

Contreras, Darwin (Universidad de Chile)

Piña, Ricardo (Universidad de Chile)

Lourenci, Mychael (Universidad de Chile)

Figueiredo, Claudia (Universidad de Chile)

Ferreira, Sergio (Universidad de Chile)

Rozas, Carlos (Universidad de Chile)

Morales, Bernardo (Universidad de Chile)

Plate, Lars (Universidad de Chile)

Gonzalez-Billault, Christian (Universidad de Chile)

Palacios, Adrian (Universidad de Chile)

Grant Number:

2018-AARG-591107

Grant Number:

ID20I10152

Grant Number:

1161524

Grant Number:

11180186

Grant Number:

15150012

Grant Number:

P09-015-F

Grant Number:

ID16I10223

Grant Number:

441921/2016-7

Grant Number:

734749

Distributor:

Repositorio de datos de investigación de la Universidad de Chile

Access Authority:

Hetz, Claudio

Depositor:

Hetz, Claudio

Date of Deposit:

2021-12-30

Holdings Information:

https://doi.org/10.34691/FK2/VUWSYP

Study Scope

Keywords:

Medicine, Health and Life Sciences, Proteostasis, UPR, Alzheimer

Abstract:

Alteration in the buffering capacity of the proteostasis network is an emerging feature of Alzheimer´s disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) is the main signaling pathway emerging from the ER to cope with protein folding stress. Inositol requiring enzyme-1 (IRE1) is an ER-located kinase and endoribonuclease that operates as a central ER stress sensor, enabling the establishment of adaptive programs through the control of the expression of the transcription factor X-Box binding protein 1 (XBP1). A polymorphism in the XBP1 promoter was suggested as a risk factor to develop AD. To artificially enforce the adaptive capacity of the UPR, here we developed strategies to express the active form of XBP1 in neurons on a preclinical model of AD. The overexpression of XBP1s in the nervous system using transgenic mice significantly reduced the load of amyloid deposition in cerebral cortex and hippocampus, in addition to preserve synaptic and cognitive function. Moreover, the local delivery of XBP1s in the hippocampus of AD mice using viral vectors improved long-term potentiation, memory performance and the density of dendritic spines. Quantitative proteomics of hippocampus indicated that XBP1 expression restores the levels of many synaptic protein and factors involved in actin cytoskeleton regulation and axonal growth. Our results illustrate the therapeutic potential of XBP1s-deppedent responses as a strategy to ameliorate AD features and sustain synaptic function.

Methodology and Processing

Sources Statement

Data Access

Other Study Description Materials

File Description--f213

File: AbO prep 512 SEC Paper-2.tab

  • Number of cases: 3552

  • No. of variables per record: 17

  • Type of File: text/tab-separated-values

Notes:

UNF:6:jy4TLL1SsU0EVRg3bFxghg==

File Description--f198

File: BM behavior 6 Months Paper 2021.tab

  • Number of cases: 254

  • No. of variables per record: 29

  • Type of File: text/tab-separated-values

Notes:

UNF:6:OopLmA5uH/swWc8z1MQUMw==

File Description--f212

File: BM behavior 8 month Paper 2021-2.tab

  • Number of cases: 51

  • No. of variables per record: 26

  • Type of File: text/tab-separated-values

Notes:

UNF:6:+fV+OW8hlMNE0MWLymXcBw==

File Description--f207

File: Cuantificación y análisis Figura 5C y D.tab

  • Number of cases: 35

  • No. of variables per record: 8

  • Type of File: text/tab-separated-values

Notes:

UNF:6:0+EGonEe6xZ1dOB9GNn30g==

File Description--f203

File: MWM behavior 6 Months Paper 2021.tab

  • Number of cases: 105

  • No. of variables per record: 39

  • Type of File: text/tab-separated-values

Notes:

UNF:6:rHnOWlm21TG1Q/q8xbVlGA==

File Description--f208

File: MWM behavior 9 Months Paper 2021.tab

  • Number of cases: 110

  • No. of variables per record: 39

  • Type of File: text/tab-separated-values

Notes:

UNF:6:s4HVRv9AIjW15PzemhDvig==

File Description--f215

File: Y Maze behavior Paper 2021.tab

  • Number of cases: 7

  • No. of variables per record: 15

  • Type of File: text/tab-separated-values

Notes:

UNF:6:lJi/J6J/TGwz+4+yf/m/Tg==

File Description--f227

File: human_datasets.tab

  • Number of cases: 23655

  • No. of variables per record: 3

  • Type of File: text/tab-separated-values

Notes:

UNF:6:P27fM1HtfEb+7Oi4/m4Ofg==

File Description--f206

File: linear_model_results.tab

  • Number of cases: 4687

  • No. of variables per record: 9

  • Type of File: text/tab-separated-values

Notes:

UNF:6:pDf88qiZ9BWs4laMqTfHeg==

File Description--f216

File: raw_panel_b.tab

  • Number of cases: 226

  • No. of variables per record: 4

  • Type of File: text/tab-separated-values

Notes:

UNF:6:DOhN5am6XMvTp8TA0bfNWg==

Variable Description

List of Variables:
  • AβOs - AβOs
  • B - B
  • C - C
  • D - D
  • E - E
  • F - F
  • Veículo - Veículo
  • H - H
  • I - I
  • J - J
  • K - K
  • L - L
  • M - M
  • N - N
  • O - O
  • P - P
  • Q - Q
  • A - A
  • B - B
  • C - C
  • D - D
  • E - E
  • F - F
  • G - G
  • H - H
  • I - I
  • J - J
  • K - K
  • L - L
  • M - M
  • N - N
  • O - O
  • P - P
  • Q - Q
  • R - R
  • S - S
  • T - T
  • U - U
  • V - V
  • W - W
  • X - X
  • Y - Y
  • Z - Z
  • AA - AA
  • AB - AB
  • AC - AC
  • A - A
  • B - B
  • C - C
  • D - D
  • E - E
  • F - F
  • Day1 - Day1
  • H - H
  • I - I
  • J - J
  • Day2 - Day2
  • L - L
  • M - M
  • Day3 - Day3
  • O - O
  • P - P
  • Day4 - Day4
  • R - R
  • S - S
  • Day5 - Day5
  • Day12 - Day12
  • Promedio - Promedio
  • W - W
  • X - X
  • Y - Y
  • Extras - Extras
  • A - A
  • B - B
  • C - C
  • MuestrasHipocampo - MuestrasHipocampo
  • E - E
  • F - F
  • G - G
  • H - H
  • MWM6meses - MWM6meses
  • B - B
  • C - C
  • D - D
  • E - E
  • F - F
  • G - G
  • H - H
  • I - I
  • J - J
  • K - K
  • L - L
  • M - M
  • N - N
  • O - O
  • P - P
  • Q - Q
  • R - R
  • S - S
  • T - T
  • U - U
  • V - V
  • W - W
  • X - X
  • Y - Y
  • Z - Z
  • AA - AA
  • AB - AB
  • AC - AC
  • AD - AD
  • AE - AE
  • AF - AF
  • AG - AG
  • AH - AH
  • AI - AI
  • AJ - AJ
  • AK - AK
  • AL - AL
  • AM - AM
  • MWM9meses - MWM9meses
  • B - B
  • C - C
  • D - D
  • E - E
  • F - F
  • G - G
  • H - H
  • I - I
  • J - J
  • K - K
  • L - L
  • M - M
  • N - N
  • O - O
  • P - P
  • Q - Q
  • R - R
  • S - S
  • T - T
  • U - U
  • V - V
  • W - W
  • X - X
  • Y - Y
  • Z - Z
  • AA - AA
  • AB - AB
  • AC - AC
  • AD - AD
  • AE - AE
  • AF - AF
  • AG - AG
  • AH - AH
  • AI - AI
  • AJ - AJ
  • AK - AK
  • AL - AL
  • AM - AM
  • A - A
  • B - B
  • C - C
  • D - D
  • E - E
  • F - F
  • G - G
  • H - H
  • I - I
  • J - J
  • K - K
  • L - L
  • M - M
  • N - N
  • O - O
  • symbol - symbol
  • logfc - logfc
  • group - group
  • control - control
  • mutant - mutant
  • uniprot - uniprot
  • symbol - symbol
  • logfc - logfc
  • pvalue - pvalue
  • fdr - fdr
  • qvalue - qvalue
  • score - score
  • control - control
  • mutant - mutant
  • direction - direction
  • go term - go term

Variables

AβOs

f213 Location:

Variable Format: character

Notes: UNF:6:MEo0ZgsuNWbhNPpNjrn2ow==

B

f213 Location:

Variable Format: character

Notes: UNF:6:D9dXJvbKSzSO39Ppih/mqA==

C

f213 Location:

Variable Format: character

Notes: UNF:6:JV2O8P+0tzeb9lZ9m4PP5w==

D

f213 Location:

Summary Statistics: Max. NaN; Mean NaN; StDev NaN; Valid 0.0; Min. NaN;

Variable Format: numeric

Notes: UNF:6:KAPyUCVhdcedUllC/zd0Ow==

E

f213 Location:

Summary Statistics: Valid 0.0; StDev NaN; Mean NaN; Max. NaN; Min. NaN

Variable Format: numeric

Notes: UNF:6:KAPyUCVhdcedUllC/zd0Ow==

F

f213 Location:

Summary Statistics: Mean NaN; Valid 0.0; Max. NaN; StDev NaN; Min. NaN

Variable Format: numeric

Notes: UNF:6:KAPyUCVhdcedUllC/zd0Ow==

Veículo

f213 Location:

Variable Format: character

Notes: UNF:6:1lNJXDovFFtP+GgxkZq1FQ==

H

f213 Location:

Variable Format: character

Notes: UNF:6:wcwp7nzHRCECSQhx8liXsg==

I

f213 Location:

Summary Statistics: Min. NaN; Mean NaN; Max. NaN; StDev NaN; Valid 0.0

Variable Format: numeric

Notes: UNF:6:KAPyUCVhdcedUllC/zd0Ow==

J

f213 Location:

Summary Statistics: Valid 0.0; StDev NaN; Min. NaN; Max. NaN; Mean NaN

Variable Format: numeric

Notes: UNF:6:KAPyUCVhdcedUllC/zd0Ow==

K

f213 Location:

Summary Statistics: Valid 0.0; Min. NaN; Max. NaN; StDev NaN; Mean NaN;

Variable Format: numeric

Notes: UNF:6:KAPyUCVhdcedUllC/zd0Ow==

L

f213 Location:

Variable Format: character

Notes: UNF:6:fOhjslep2jAiV0rGswMcaA==

M

f213 Location:

Summary Statistics: Mean 18075.401443642375; StDev 53853.04146085782; Min. -379.0; Max. 513716.0; Valid 1801.0

Variable Format: numeric

Notes: UNF:6:Pr+2XZQJKb5AzGHJV1TCMg==

N

f213 Location:

Summary Statistics: Mean NaN; StDev NaN; Valid 0.0; Max. NaN; Min. NaN;

Variable Format: numeric

Notes: UNF:6:KAPyUCVhdcedUllC/zd0Ow==

O

f213 Location:

Variable Format: character

Notes: UNF:6:uAGu4B7mk/IfTPTn5jfI3g==

P

f213 Location:

Summary Statistics: StDev 4648.696108682824; Mean 318.51915602442557; Max. 4500.0; Min. -137394.0; Valid 1801.0;

Variable Format: numeric

Notes: UNF:6:fMlw+vL4H7i/5gCy9Gqxdw==

Q

f213 Location:

Summary Statistics: Mean NaN; Max. NaN; Valid 0.0; Min. NaN; StDev NaN;

Variable Format: numeric

Notes: UNF:6:KAPyUCVhdcedUllC/zd0Ow==

A

f198 Location:

Variable Format: character

Notes: UNF:6:MuaqQEnbZr0g32ul0sKzIg==

B

f198 Location:

Variable Format: character

Notes: UNF:6:4pXXPS70xYCQDxbaTjkLZw==

C

f198 Location:

Variable Format: character

Notes: UNF:6:nP7aP8E8ZOGPxl6H7HVDbw==

D

f198 Location:

Variable Format: character

Notes: UNF:6:UPJo+MQjeFFKhg6I9lmo1A==

E

f198 Location:

Summary Statistics: Mean NaN; Max. NaN; Min. NaN; Valid 0.0; StDev NaN

Variable Format: numeric

Notes: UNF:6:PRZzfg3V+uoFRO7a88E0cw==

F

f198 Location:

Variable Format: character

Notes: UNF:6:HPa0rKN4/DZtAsr/RCCxtw==

G

f198 Location:

Variable Format: character

Notes: UNF:6:SoKLsbxJd4tnwAcGfCW4oA==

H

f198 Location:

Variable Format: character

Notes: UNF:6:jYyzJidxOnJDDliJEwRY2A==

I

f198 Location:

Variable Format: character

Notes: UNF:6:OOXL3fL8SjLtc0i8vq4k2w==

J

f198 Location:

Variable Format: character

Notes: UNF:6:b/ocIMxig4eajWsbCTAzng==

K

f198 Location:

Variable Format: character

Notes: UNF:6:I2BEwxzB3Cp5vjfJnJ021A==

L

f198 Location:

Variable Format: character

Notes: UNF:6:20+iw4IKwpeORcBUk8pt3A==

M

f198 Location:

Variable Format: character

Notes: UNF:6:5BSgEI6AEGJ2AsOvAN/k4A==

N

f198 Location:

Variable Format: character

Notes: UNF:6:3u7Sf2ogwu9yzZ2NJSMVOw==

O

f198 Location:

Variable Format: character

Notes: UNF:6:C65wZehP4cF90WjjxxARyw==

P

f198 Location:

Variable Format: character

Notes: UNF:6:INSo72u8lsIX8A0wPjysyQ==

Q

f198 Location:

Variable Format: character

Notes: UNF:6:Cs9ylrzUpHY+Q2T+TGwFNg==

R

f198 Location:

Variable Format: character

Notes: UNF:6:O0PRkCOnp80gPCSNQrMqIQ==

S

f198 Location:

Variable Format: character

Notes: UNF:6:AhLaqtEZ86Vo3aFjKY1BYA==

T

f198 Location:

Variable Format: character

Notes: UNF:6:b/UJSPbR8X5qRcLD79d+0Q==

U

f198 Location:

Variable Format: character

Notes: UNF:6:Ttq2DT+E+McFNYipq3mcWw==

V

f198 Location:

Variable Format: character

Notes: UNF:6:ysVpDK56KdXkbpdYBtPQPQ==

W

f198 Location:

Variable Format: character

Notes: UNF:6:lDsZhRY4C5zIDhBq2OAzhA==

X

f198 Location:

Variable Format: character

Notes: UNF:6:rvMlTEDp4TuB41+3rA8Xjw==

Y

f198 Location:

Variable Format: character

Notes: UNF:6:1L5t0txfjkpsr6sZEyPBdw==

Z

f198 Location:

Variable Format: character

Notes: UNF:6:ckg2QdK13bJqRsa5/v+e9g==

AA

f198 Location:

Variable Format: character

Notes: UNF:6:1XQlI0d/sOVGmsWfD+2gkg==

AB

f198 Location:

Variable Format: character

Notes: UNF:6:aX0SC1rnHxLiU7DQIosTMA==

AC

f198 Location:

Variable Format: character

Notes: UNF:6:GJchIQoUQL+52XDVUXzmPw==

A

f212 Location:

Summary Statistics: Max. NaN; Valid 0.0; StDev NaN; Mean NaN; Min. NaN

Variable Format: numeric

Notes: UNF:6:8WY8zutnujXFpcv1i1YFDQ==

B

f212 Location:

Variable Format: character

Notes: UNF:6:LVmTNH8/AqWscttBLCMZBg==

C

f212 Location:

Variable Format: character

Notes: UNF:6:S8fxWL7jNk8WlCSWXq0YBA==

D

f212 Location:

Variable Format: character

Notes: UNF:6:P9yzamwSk9GSOjVC9WCWIQ==

E

f212 Location:

Variable Format: character

Notes: UNF:6:bhNp2rXvmc3PnztnjcjIRw==

F

f212 Location:

Variable Format: character

Notes: UNF:6:O/2mN2oFVxCWVYXMZFNp6w==

Day1

f212 Location:

Variable Format: character

Notes: UNF:6:YUlQMhzquKS/IOMi7Ma4wA==

H

f212 Location:

Variable Format: character

Notes: UNF:6:zVSNpakAw99FDcZNz/tncw==

I

f212 Location:

Variable Format: character

Notes: UNF:6:7yNiFcvPD9J1qAIxhtVWbA==

J

f212 Location:

Variable Format: character

Notes: UNF:6:NZ9JqOeuAdZ44p7TU96x+A==

Day2

f212 Location:

Variable Format: character

Notes: UNF:6:tLvhx0BDYtWE0RdAqjUt6Q==

L

f212 Location:

Variable Format: character

Notes: UNF:6:Mnu4UrtYi5f49QH4Mfqtqw==

M

f212 Location:

Variable Format: character

Notes: UNF:6:ckqIRsEJCZWxHiOqAXidbg==

Day3

f212 Location:

Variable Format: character

Notes: UNF:6:jf5b5UX+6vmn2p2gPZ3mxw==

O

f212 Location:

Variable Format: character

Notes: UNF:6:HNUtkV4Xt58WCxRflj4klQ==

P

f212 Location:

Variable Format: character

Notes: UNF:6:l8f5McFBTNt3QX0iOJ/3xA==

Day4

f212 Location:

Variable Format: character

Notes: UNF:6:HjGRTTgiCq950hLa05Du3g==

R

f212 Location:

Variable Format: character

Notes: UNF:6:99qaH7BjZkzN80gZQ5HXug==

S

f212 Location:

Variable Format: character

Notes: UNF:6:4VROnrr5tNmoNpDKkkWdBg==

Day5

f212 Location:

Variable Format: character

Notes: UNF:6:WrcLMrCUIFd8eWqBsHpDVQ==

Day12

f212 Location:

Variable Format: character

Notes: UNF:6:TxZ1SKaszLVnXQEZiP3LKw==

Promedio

f212 Location:

Variable Format: character

Notes: UNF:6:xGoK7QLPfGs2DfAbFykDWA==

W

f212 Location:

Variable Format: character

Notes: UNF:6:rdlp26T+oytnmuJwOJ5Cgg==

X

f212 Location:

Variable Format: character

Notes: UNF:6:TVCOzNAqZj4hNRhpoZSVNA==

Y

f212 Location:

Variable Format: character

Notes: UNF:6:udRiHTrBtde0PQ/jhN8EBA==

Extras

f212 Location:

Variable Format: character

Notes: UNF:6:mYPWCtU89vldzfkss3tN8g==

A

f207 Location:

Summary Statistics: Max. NaN; Min. NaN; StDev NaN; Mean NaN; Valid 0.0

Variable Format: numeric

Notes: UNF:6:UjxBRk7kfWE1DhW8CRvJcA==

B

f207 Location:

Variable Format: character

Notes: UNF:6:MdsidZma6P6Hby4cWTlCqw==

C

f207 Location:

Variable Format: character

Notes: UNF:6:L6ZZ+5yVDIAq6wwCaBFzMg==

MuestrasHipocampo

f207 Location:

Variable Format: character

Notes: UNF:6:gtn9ziOQB6YXMZZHa0mxXw==

E

f207 Location:

Variable Format: character

Notes: UNF:6:JNddd5TC8acs4zmiLLBGgw==

F

f207 Location:

Variable Format: character

Notes: UNF:6:sCB60adgTgC2xeP4T0aPsg==

G

f207 Location:

Variable Format: character

Notes: UNF:6:CcEuq8U7D7F30/QwyqMjoQ==

H

f207 Location:

Variable Format: character

Notes: UNF:6:DtJiE3vbHTFi1sxpGF+C7g==

MWM6meses

f203 Location:

Variable Format: character

Notes: UNF:6:7t0/419g0VFD25SZK3aerQ==

B

f203 Location:

Variable Format: character

Notes: UNF:6:sVhd/4k0oMUtF2xI9EaCwQ==

C

f203 Location:

Variable Format: character

Notes: UNF:6:mxSXiZ3OwyW5/5Q1uEZnpA==

D

f203 Location:

Variable Format: character

Notes: UNF:6:KbtodrIxacGSmaHRs3perQ==

E

f203 Location:

Summary Statistics: Valid 0.0; Max. NaN; Min. NaN; Mean NaN; StDev NaN;

Variable Format: numeric

Notes: UNF:6:AxRBQryH1cg7Et7FupUBHA==

F

f203 Location:

Variable Format: character

Notes: UNF:6:Kpui96cOsFc0pRFn/TSpjQ==

G

f203 Location:

Variable Format: character

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