Adaptor protein interactions: Modulators of amyloid precursor protein metabolism and Alzheimer's disease risk?

Gwendalyn D. King; R. Scott Turner

doi:10.1016/j.expneurol.2003.10.011

Adaptor protein interactions: Modulators of amyloid precursor protein metabolism and Alzheimer's disease risk?

Gwendalyn D. King, R. Scott Turner

Research output: Contribution to journal › Review article › peer-review

138 Scopus citations

Abstract

The cytoplasmic C-terminus of APP plays critical roles in its cellular trafficking and delivery to proteases. Adaptor proteins with phosphotyrosine-binding (PTB) domains, including those in the X11, Fe65, and c-Jun N-terminal kinase (JNK)-interacting protein (JIP) families, bind specifically to the absolutely conserved -YENPTY- motif in the APP C-terminus to regulate its trafficking and processing. Compounds that modulate APP-adaptor protein interactions may inhibit Aβ generation by specifically targeting the substrate (APP) instead of the enzyme (β- or γ-secretase). Genetic polymorphisms in (or near) adaptor proteins may influence risk of sporadic AD by interacting with APP in vivo to modulate its trafficking and processing to Aβ.

Original language	English (US)
Pages (from-to)	208-219
Number of pages	12
Journal	Experimental Neurology
Volume	185
Issue number	2
DOIs	https://doi.org/10.1016/j.expneurol.2003.10.011
State	Published - Feb 2004
Externally published	Yes

All Science Journal Classification (ASJC) codes

Neurology
Developmental Neuroscience

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10.1016/j.expneurol.2003.10.011

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title = "Adaptor protein interactions: Modulators of amyloid precursor protein metabolism and Alzheimer's disease risk?",

abstract = "The cytoplasmic C-terminus of APP plays critical roles in its cellular trafficking and delivery to proteases. Adaptor proteins with phosphotyrosine-binding (PTB) domains, including those in the X11, Fe65, and c-Jun N-terminal kinase (JNK)-interacting protein (JIP) families, bind specifically to the absolutely conserved -YENPTY- motif in the APP C-terminus to regulate its trafficking and processing. Compounds that modulate APP-adaptor protein interactions may inhibit Aβ generation by specifically targeting the substrate (APP) instead of the enzyme (β- or γ-secretase). Genetic polymorphisms in (or near) adaptor proteins may influence risk of sporadic AD by interacting with APP in vivo to modulate its trafficking and processing to Aβ.",

author = "King, {Gwendalyn D.} and Turner, {R. Scott}",

note = "Funding Information: This work was supported by grants from the American Federation for Aging Research, Alzheimer's Association, NIA (P50 AG08671), NINDS (National Research Service Award to G.D. King), and by the VA Ann Arbor Healthcare System Geriatric Research Education and Clinical Center.",

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doi = "10.1016/j.expneurol.2003.10.011",

language = "English (US)",

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T2 - Modulators of amyloid precursor protein metabolism and Alzheimer's disease risk?

AU - King, Gwendalyn D.

AU - Turner, R. Scott

N1 - Funding Information: This work was supported by grants from the American Federation for Aging Research, Alzheimer's Association, NIA (P50 AG08671), NINDS (National Research Service Award to G.D. King), and by the VA Ann Arbor Healthcare System Geriatric Research Education and Clinical Center.

PY - 2004/2

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N2 - The cytoplasmic C-terminus of APP plays critical roles in its cellular trafficking and delivery to proteases. Adaptor proteins with phosphotyrosine-binding (PTB) domains, including those in the X11, Fe65, and c-Jun N-terminal kinase (JNK)-interacting protein (JIP) families, bind specifically to the absolutely conserved -YENPTY- motif in the APP C-terminus to regulate its trafficking and processing. Compounds that modulate APP-adaptor protein interactions may inhibit Aβ generation by specifically targeting the substrate (APP) instead of the enzyme (β- or γ-secretase). Genetic polymorphisms in (or near) adaptor proteins may influence risk of sporadic AD by interacting with APP in vivo to modulate its trafficking and processing to Aβ.

AB - The cytoplasmic C-terminus of APP plays critical roles in its cellular trafficking and delivery to proteases. Adaptor proteins with phosphotyrosine-binding (PTB) domains, including those in the X11, Fe65, and c-Jun N-terminal kinase (JNK)-interacting protein (JIP) families, bind specifically to the absolutely conserved -YENPTY- motif in the APP C-terminus to regulate its trafficking and processing. Compounds that modulate APP-adaptor protein interactions may inhibit Aβ generation by specifically targeting the substrate (APP) instead of the enzyme (β- or γ-secretase). Genetic polymorphisms in (or near) adaptor proteins may influence risk of sporadic AD by interacting with APP in vivo to modulate its trafficking and processing to Aβ.

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Adaptor protein interactions: Modulators of amyloid precursor protein metabolism and Alzheimer's disease risk?

Abstract

All Science Journal Classification (ASJC) codes

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