Last update 01 Nov 2024

Amyloid precursor protein secretases

Last update 01 Nov 2024

Basic Info

Synonyms-

Introduction-

Drugs associated with Amyloid precursor protein secretases

EVP-15962

Target

Amyloid precursor protein secretases

Mechanism

Amyloid precursor protein secretases inhibitors

Active Org.-

Originator Org.

EnVivo Pharmaceuticals

Active Indication-

Inactive Indication

Alzheimer Disease

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ITI-009 series

Target

Amyloid precursor protein secretases

Mechanism

Amyloid precursor protein secretases inhibitors

Active Org.-

Originator Org.

Intra-Cellular Therapies, Inc.

Active Indication-

Inactive Indication

Alzheimer Disease

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ACD-679

Target

Amyloid precursor protein secretases

Mechanism

Amyloid precursor protein secretases modulators

Active Org.-

Originator Org.

AlzeCure Pharma AB

Active Indication-

Inactive Indication

Alzheimer Disease

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Amyloid precursor protein secretases

100 Translational Medicine associated with Amyloid precursor protein secretases

0 Patents (Medical) associated with Amyloid precursor protein secretases

Literatures (Medical) associated with Amyloid precursor protein secretases

16 Jul 2024·Annual Review of Biophysics

Cholesterol and Lipid Rafts in the Biogenesis of Amyloid-β Protein and Alzheimer's Disease

Review

Author: Abraham, Conor B ; Straub, John E ; Pantelopulos, George A

Cholesterol has been conjectured to be a modulator of the amyloid cascade, the mechanism that produces the amyloid-β (Aβ) peptides implicated in the onset of Alzheimer's disease. We propose that cholesterol impacts the genesis of Aβ not through direct interaction with proteins in the bilayer, but indirectly by inducing the liquid-ordered phase and accompanying liquid–liquid phase separations, which partition proteins in the amyloid cascade to different lipid domains and ultimately to different endocytotic pathways. We explore the full process of Aβ genesis in the context of liquid-ordered phases induced by cholesterol, including protein partitioning into lipid domains, mechanisms of endocytosis experienced by lipid domains and secretases, and pH-controlled activation of amyloid precursor protein secretases in specific endocytotic environments. Outstanding questions on the essential role of cholesterol in the amyloid cascade are identified for future studies.

01 Sep 2021·Cell SystemsQ1 · BIOLOGY

Dysregulation of the secretory pathway connects Alzheimer’s disease genetics to aggregate formation

Q1 · BIOLOGY

Article

Author: Austin W.T. Chiang ; Nathan E. Lewis ; Hratch M. Baghdassarian ; Chih-Chung Kuo

Amyloid disorders such as Alzheimer's disease (AD) involve the aggregation of secreted proteins. However, it is largely unclear how secretory-pathway proteins contribute to amyloid formation. We developed a systems biology framework integrating expression data with protein-protein interaction networks to estimate a tissue's fitness for producing specific secreted proteins and analyzed the fitness of the secretory pathway of various brain regions and cell types for synthesizing the AD-associated amyloid precursor protein (APP). While key amyloidogenic pathway components were not differentially expressed in AD brains, we found Aβ deposition correlates with systemic down- and upregulation of the secretory-pathway components proximal to APP and amyloidogenic secretases, respectively, in AD. Our analyses suggest that perturbations from three AD risk loci cascade through the APP secretory-support network and into the endocytosis pathway, connecting amyloidogenesis to dysregulation of secretory-pathway components supporting APP and suggesting novel therapeutic targets for AD. A record of this paper's transparent peer review process is included in the supplemental information.

01 May 2021·NeuroscienceQ3 · MEDICINE

MicroRNA-4422-5p as a Negative Regulator of Amyloidogenic Secretases: A Potential Biomarker for Alzheimer’s Disease

Q3 · MEDICINE

Article

Author: Sadigh-Eteghad, Saeed ; Teimourian, Shahram ; Mehdizadeh, Mehdi ; Shanehbandi, Dariush ; Shahbazi, Ali ; Hajjari, Seyedeh Nazanin

Beta-secretase (BACE1) and gamma-secretase activating protein (GSAP) are pivotal enzymes in the cleavage of amyloid precursor protein (APP). Beta-amyloid (Aß) formation is considered one of the main reasons for Alzheimer's disease (AD) pathology. In our preliminary study, a series of microRNAs (miRs) with possible interaction with BACE1 and/or GSAP was selected using computational analysis. Our results showed that miR-4422-5p had a reduced level in the serum of AD patients. In this study, the effect of miR-4422-5p using miR-4422-5p mimic and inhibitor on BACE1 and GSAP were investigated, and a probable novel early diagnostic marker for AD was introduced. The effect of miR-4422-5p interaction with BACE1 and GSAP was evaluated via in vitro experiments using dual-luciferase assays, western blotting, and Immunocytochemistry. Luciferase assay demonstrated that miR-4422-5p mimic suppresses BACE1 and GSAP expression by directly targeting the 3'UTR of BACE1 and GSAP mRNA in HEK293T cells. Also, western blotting and immunocytochemistry confirmed the regulatory role of miR-4422-5p mimic on BACE1 and GSAP genes. miR-4422-5p mimic significantly decreased BACE1 and GSAP protein expression in SH-SY5Y and A549 cells, respectively. Moreover, miR-4422-5p-inhibitor reversed the expression processes in both cell lines. Our data suggest that miR-4422-5p may be an important regulator of both BACE1 and GSAP genes and can represent a novel potential biomarker or therapeutic target in AD.

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Amyloid precursor protein secretases

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