scholarly journals Cellular Functions of the Amyloid Precursor Protein from Development to Dementia

2015 ◽  
Vol 32 (4) ◽  
pp. 502-515 ◽  
Author(s):  
Rik van der Kant ◽  
Lawrence S.B. Goldstein
Keyword(s):  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Cellular Functions

scholarly journals The Amyloid Precursor Protein C99 Fragment Modulates Voltage-Gated Potassium Channels.

2021 ◽  
Vol 55 (S3) ◽  
pp. 157-170
Keyword(s):  
Amyloid Precursor Protein ◽  
Protein Interactions ◽  
Precursor Protein ◽  
Xenopus Laevis Oocytes ◽  
Cellular Functions ◽  
Voltage Gated ◽  
Adult Rat ◽  
Kv Channel ◽  
Kv Channels

BACKGROUND/AIMS: The Amyloid Precursor Protein (APP) is involved in the regulation of multiple cellular functions via protein-protein interactions and has been most studied with respect to Alzheimer's disease (AD). Abnormal processing of the single transmembrane-spanning C99 fragment of APP contributes to the formation of amyloid plaques, which are causally related to AD. Pathological C99 accumulation is thought to associate with early cognitive defects in AD. Here, unexpectedly, sequence analysis revealed that C99 exhibits 24% sequence identity with the KCNE1 voltage-gated potassium (Kv) channel β subunit, comparable to the identity between KCNE1 and KCNE2-5 (21-30%). This suggested the possibility of C99 regulating Kv channels. METHODS: We quantified the effects of C99 on Kv channel function, using electrophysiological analysis of subunits expressed in Xenopus laevis oocytes, biochemical and immunofluorescence techniques. RESULTS: C99 isoform-selectively inhibited (by 30-80%) activity of a range of Kv channels. Among the KCNQ (Kv7) family, C99 isoform-selectively inhibited, shifted the voltage dependence and/or slowed activation of KCNQ2, KCNQ3, KCNQ2/3 and KCNQ5, with no effects on KCNQ1, KCNQ1-KCNE1 or KCNQ4. C99/APP co-localized with KCNQ2 and KCNQ3 in adult rat sciatic nerve nodes of Ranvier. Both C99 and full-length APP co-immunoprecipitated with KCNQ2 in vitro, yet unlike C99, APP only weakly affected KCNQ2/3 activity. Finally, C99 altered the effects on KCNQ2/3 function of inhibitors tetraethylammounium and XE991, but not openers retigabine and ICA27243.

Memapsin 2, a drug target for Alzheimer's disease

2003 ◽  
Vol 70 ◽  
pp. 213-220 ◽  
Author(s):  
Gerald Koelsch ◽  
Robert T. Turner ◽  
Lin Hong ◽  
Arun K. Ghosh ◽  
Jordan Tang
Keyword(s):  
Crystal Structure ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transition State ◽  
Amyloid Precursor Protein ◽  
Therapeutic Target ◽  
Drug Target ◽  
Aspartic Protease ◽  
Precursor Protein ◽  
Memapsin 2

Mempasin 2, a ϐ-secretase, is the membrane-anchored aspartic protease that initiates the cleavage of amyloid precursor protein leading to the production of ϐ-amyloid and the onset of Alzheimer's disease. Thus memapsin 2 is a major therapeutic target for the development of inhibitor drugs for the disease. Many biochemical tools, such as the specificity and crystal structure, have been established and have led to the design of potent and relatively small transition-state inhibitors. Although developing a clinically viable mempasin 2 inhibitor remains challenging, progress to date renders hope that memapsin 2 inhibitors may ultimately be useful for therapeutic reduction of ϐ-amyloid.

Interplay between Pur α and Egr-1 in the transcriptional regulation of amyloid precursor protein gene expression

2010 ◽  
Vol 34 (8) ◽  
pp. S27-S27
Author(s):  
Jianqi Cui ◽  
Xiuying Pei ◽  
Qian Zhang ◽  
Bassel E. Sawaya ◽  
Xiaohong Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Amyloid Precursor Protein ◽  
Protein Gene ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Gene

Insulinrezeptorsubstrat (IRS)2-Expression moduliert die Amyloid-Precursor-Protein (APP) Spaltung in vivo

2010 ◽  
Vol 5 (S 01) ◽  
Author(s):  
M Udelhoven ◽  
T Ehlkes ◽  
MM Hettich ◽  
S Asrat ◽  
W Krone ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Precursor Protein

Structural and Dynamic Study of the Transmembrane Domain of the Amyloid Precursor Protein

Acta Naturae ◽  
2011 ◽  
Vol 3 (1) ◽  
pp. 69-76 ◽  
Author(s):  
K D Nadezhdin ◽  
O V Bocharova ◽  
E V Bocharov ◽  
A S Arseniev
Keyword(s):  
Amyloid Precursor Protein ◽  
Transmembrane Domain ◽  
Dynamic Study ◽  
Precursor Protein
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