Cycle on Wheels: Is APP Key to the AppBp1 Pathway?

Overview

Journal Austin Alzheimers Parkinsons Dis

Publisher Austin Publishing Group

Date 2015 Jan 9

PMID 25568892

Citations 7

Authors

Y Chen

Rn Neve

H Zheng

Wts Griffin

Sw Barger

Re Mrak

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease (AD) is the gradual loss of the cognitive function due to neuronal death. Currently no therapy is available to slow down, reverse or prevent the disease. Here we analyze the existing data in literature and hypothesize that the physiological function of the Amyloid Precursor Protein (APP) is activating the AppBp1 pathway and this function is gradually lost during the progression of AD pathogenesis. The AppBp1 pathway, also known as the neddylation pathway, activates the small ubiquitin-like protein nedd8, which covalently modifies and switches on Cullin ubiquitin ligases, which are essential in the turnover of cell cycle proteins. Here we discuss how APP may activate the AppBp1 pathway, which downregulates cell cycle markers and protects genome integrity. More investigation of this mechanism-driven hypothesis may provide insights into disease treatment and prevention strategies.

Citing Articles

Role of Neddylation in Neurodegenerative Diseases.

Govindarajulu M, Ramesh S, Shankar T, Kora M, Moore T, Dhanasekaran M NeuroSci. 2024; 3(4):533-545.

PMID: 39483771 PMC: 11523694. DOI: 10.3390/neurosci3040038.

Targeting neddylation E2s: a novel therapeutic strategy in cancer.

Zheng Y, Guo Y, Wang B, Wang C, Mamun M, Gao Y J Hematol Oncol. 2021; 14(1):57.

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Ablation of amyloid precursor protein increases insulin-degrading enzyme levels and activity in brain and peripheral tissues.

Kulas J, Franklin W, Smith N, Manocha G, Puig K, Nagamoto-Combs K Am J Physiol Endocrinol Metab. 2018; 316(1):E106-E120.

PMID: 30422705 PMC: 6417684. DOI: 10.1152/ajpendo.00279.2018.

Clinical significance of ubiquilin 1 in gastric cancer.

Bao J, Jiang X, Zhu X, Dai G, Dou R, Liu X Medicine (Baltimore). 2018; 97(3):e9701.

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Taming Alzheimer's disease: New perspectives, newer horizons.

Sen D, Majumder A, Arora V, Yadu N, Chakrabarti R Iran J Neurol. 2017; 16(3):146-155.

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