NDLI: Modulation of BAG3 Expression and Proteasomal Activity by sAPPα Does Not Require Membrane-Tethered Holo-APP

Content Provider	Springer Nature Link
Author	Kundu, Arpita Milosch, Nelli Antonietti, Patrick Baumkötter, Frederik Zymny, Andreas Müller, Ulrike C. Kins, Stefan Hajieva, Parvana Behl, Christian Kögel, Donat
Copyright Year	2015
Abstract	Maintenance of intracellular proteostasis is essential for neuronal function, and emerging data support the view that disturbed proteostasis plays an important role in brain aging and the pathogenesis of age-related neurodegenerative disorders such as Alzheimer’s disease (AD). sAPPalpha (sAPPα), the extracellularly secreted N-terminal alpha secretase cleavage product of the amyloid precursor protein (APP), has an established function in neuroprotection. Recently, we provided evidence that membrane-bound holo-APP functionally cooperates with sAPPα to mediate neuroprotection via activation of the Akt survival signaling pathway and sAPPα directly affects proteostasis. Here, we demonstrate that in addition to its anti-apoptotic function, sAPPα has effects on neuronal proteostasis under conditions of proteasomal stress. In particular, recombinant sAPPα significantly suppressed MG132-triggered expression of the co-chaperone BAG3 and aggresome formation, and it partially rescued proteasomal activity in a dose-dependent manner in SH-SY5Y neuroblastoma cells. In analogy, sAPPα was able to inhibit MG132-induced BAG3 expression in primary hippocampal neurons. Strikingly, these sAPPα-induced changes were unaltered in APP-depleted SH-SY5Y cells and APP-deficient neurons, demonstrating that holo-APP is not required for this particular function of sAPPα. Importantly, recombinant sAPPbeta (sAPPβ) failed to modulate BAG3 expression and proteostasis in APP-proficient wild-type (wt) cells, indicating that these biological effects are highly selective for sAPPα. In conclusion, we demonstrate that modulation of proteostasis is a distinct biological function of sAPPα and does not require surface-bound holo-APP. Our data shed new light on the physiological functions of APP and the interplay between APP processing and proteostasis during brain aging.
Starting Page	5985
Ending Page	5994
Page Count	10
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	53
Issue Number	9
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2015-11-02
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Amyloid precursor protein Alpha secretase Autophagy Proteasome Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Adhesion of monocytes to type I collagen stimulates an APP-dependent proinflammatory signaling response and release of Aβ1-40

Cellular Membrane Fluidity in Amyloid Precursor Protein Processing

β-secretase processing of the Alzheimer’s amyloid protein precursor (APP)

ApoER2 expression increases Aβ production while decreasing Amyloid Precursor Protein (APP) endocytosis: Possible role in the partitioning of APP into lipid rafts and in the regulation of γ-secretase activity

γ-Secretase modulators exhibit selectivity for modulation of APP cleavage but inverse γ-secretase modulators do not

Bryostatin-1 vs. TPPB: Dose-Dependent APP Processing and PKC-α, -δ, and -ε Isoform Activation in SH-SY5Y Neuronal Cells

Brain Ischemia Activates β- and γ-Secretase Cleavage of Amyloid Precursor Protein: Significance in Sporadic Alzheimer’s Disease

TUDCA, a Bile Acid, Attenuates Amyloid Precursor Protein Processing and Amyloid-β Deposition in APP/PS1 Mice

Amyloid precursor protein modulates β-catenin degradation

Modulation of BAG3 Expression and Proteasomal Activity by sAPPα Does Not Require Membrane-Tethered Holo-APP

Similar Documents

Adhesion of monocytes to type I collagen stimulates an APP-dependent proinflammatory signaling response and release of Aβ1-40

Cellular Membrane Fluidity in Amyloid Precursor Protein Processing

β-secretase processing of the Alzheimer’s amyloid protein precursor (APP)

ApoER2 expression increases Aβ production while decreasing Amyloid Precursor Protein (APP) endocytosis: Possible role in the partitioning of APP into lipid rafts and in the regulation of γ-secretase activity

γ-Secretase modulators exhibit selectivity for modulation of APP cleavage but inverse γ-secretase modulators do not

Bryostatin-1 vs. TPPB: Dose-Dependent APP Processing and PKC-α, -δ, and -ε Isoform Activation in SH-SY5Y Neuronal Cells

Brain Ischemia Activates β- and γ-Secretase Cleavage of Amyloid Precursor Protein: Significance in Sporadic Alzheimer’s Disease

TUDCA, a Bile Acid, Attenuates Amyloid Precursor Protein Processing and Amyloid-β Deposition in APP/PS1 Mice

Amyloid precursor protein modulates β-catenin degradation

Modulation of BAG3 Expression and Proteasomal Activity by sAPPα Does Not Require Membrane-Tethered Holo-APP