Defining the Anterograde and Endocytic Trafficking Pathways in Primary Neurons; Relevance to Dysfunctional Trafficking of Bace1 and App in Alzheimer’s Disease

Grant number: 1163862 | Funding period: 2019 - 2022

Completed

Abstract

Alzheimer’s disease results from toxic peptides arising from the cleavage of a large molecule called APP in the brain. The production of toxic peptides is normally regulated by the transport of APP molecules between compartments inside the cell. In Alzheimer’s disease, the APP transport pathways are altered leading to high levels of toxic peptide.This research will discover the basis for the altered transport of APP in disease, information which could allow new approaches for dementia treatment.

Related publications (11)

Scholarly works icon

How Human Induced Pluripotent Stem Cells-Derived Models can Advance our Understanding of Secretion Mechanisms in Physiological and Pathological Contexts?

L Fourriere, G Boncompain

2025-10-01

The molecular architecture of differentiated cells is essential to ensure their specific functions and is supported by membrane tr..

Scholarly works icon

Spatial–Temporal Mapping Reveals the Golgi as the Major Processing Site for the Pathogenic Swedish APP Mutation: Familial APP Mutant Shifts the Major APP Processing Site

J Wang, PA Gleeson, L Fourriere

2024-03-01

Alzheimer's disease is associated with increased levels of amyloid beta (Aβ) generated by sequential intracellular cleavage of amy..

Scholarly works icon

Long-term live cell imaging during differentiation of human iPSC-derived neurons

J Wang, PA Gleeson, L Fourriere

2023-12-15

Live-cell imaging is crucial to appreciate the dynamics and the complexity of cellular interaction processes. However, live-cell i..

Scholarly works icon

Organelle mapping in dendrites of human iPSC-derived neurons reveals dynamic functional dendritic Golgi structures

J Wang, M Daniszewski, MM Hao, D Hernández, A Pébay, PA Gleeson, L Fourriere

2023-07-25

Secretory pathways within dendrites of neurons have been proposed for local transport of newly synthesized proteins. However, litt..

Scholarly works icon

Quantification of Golgi Entry and Exit Kinetics of Protein Cargoes

J Wang, EHJ Cho, PA Gleeson, L Fourriere

2023-01-01

The Golgi apparatus is a pivotal secretory organelle in membrane trafficking, a hub responsible for posttranslational modification..

Scholarly works icon

Segregation of the membrane cargoes, BACE1 and amyloid precursor protein (APP) throughout the Golgi apparatus

L Fourriere, EHJ Cho, PA Gleeson

2022-03-01

The intracellular trafficking of β-site amyloid precursor protein (APP) cleaving enzyme (BACE1) and APP regulates amyloid-β produc..

Scholarly works icon

Amyloid β production along the neuronal secretory pathway: Dangerous liaisons in the Golgi?

L Fourriere, PA Gleeson

2021-09-01

β-amyloid peptides (Aβ) are generated in intracellular compartments of neurons and secreted to form cytotoxic fibrils and plaques...

Scholarly works icon

Sorting nexin 5 mediates virus-induced autophagy and immunity

X Dong, Y Yang, Z Zou, Y Zhao, B Ci, L Zhong, M Bhave, L Wang, YC Kuo, X Zang, R Zhong, ER Aguilera, RB Richardson, B Simonetti, JW Schoggins, JK Pfeiffer, L Yu, X Zhang, Y Xie, SL Schmid

2021-01-21

Autophagy, a process of degradation that occurs via the lysosomal pathway, has an essential role in multiple aspects of immunity, ..

Scholarly works icon

Local Secretory Trafficking Pathways in Neurons and the Role of Dendritic Golgi Outposts in Different Cell Models

J Wang, L Fourriere, PA Gleeson

2020-11-26

A fundamental characteristic of neurons is the relationship between the architecture of the polarized neuron and synaptic transmis..

Scholarly works icon

Distinct anterograde trafficking pathways of BACE1 and amyloid precursor protein from the TGN and the regulation of amyloid-β production

JZA Tan, L Fourriere, J Wang, F Perez, G Boncompain, PA Gleesona

2020-01-01

Processing of amyloid precursor protein (APP) by the β-secretase BACE1 is the initial step of the amyloidogenic pathway to generat..

Scholarly works icon

The role of innate immune responses and neuroinflammation in amyloid accumulation and progression of Alzheimer's disease

A Webers, MT Heneka, PA Gleeson

2020-01-01

Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) accumulation, tau pathology and neuroinflammation. Recently, there ..

University of Melbourne Researchers