Heparan sulfate proteoglycans: Mediators of cellular and molecular Alzheimer's disease pathogenic factors via tunnelling nanotubes?

Duy L B Nguyen; Rachel K Okolicsanyi; Larisa M Haupt

doi:10.1016/j.mcn.2024.103936

Heparan sulfate proteoglycans: Mediators of cellular and molecular Alzheimer's disease pathogenic factors via tunnelling nanotubes?

Mol Cell Neurosci. 2024 May 13:129:103936. doi: 10.1016/j.mcn.2024.103936. Online ahead of print.

Authors

Duy L B Nguyen¹, Rachel K Okolicsanyi², Larisa M Haupt³

Affiliations

¹ Stem Cell and Neurogenesis Group, Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology (QUT), 60 Musk Ave., Kelvin Grove, Queensland 4059, Australia.
² Stem Cell and Neurogenesis Group, Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology (QUT), 60 Musk Ave., Kelvin Grove, Queensland 4059, Australia; ARC Training Centre for Cell and Tissue Engineering Technologies, Queensland University of Technology (QUT), Australia.
³ Stem Cell and Neurogenesis Group, Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology (QUT), 60 Musk Ave., Kelvin Grove, Queensland 4059, Australia; Centre for Biomedical Technologies, Queensland University of Technology (QUT), 60 Musk Ave., Kelvin Grove, QLD 4059, Australia; ARC Training Centre for Cell and Tissue Engineering Technologies, Queensland University of Technology (QUT), Australia; Max Planck Queensland Centre for the Materials Sciences of Extracellular Matrices, Queensland University of Technology (QUT), Australia. Electronic address: larisa.haupt@qut.edu.au.

PMID: 38750678
DOI: 10.1016/j.mcn.2024.103936

Abstract

Neurological disorders impact around one billion individuals globally (15 % approx.), with significant implications for disability and mortality with their impact in Australia currently amounts to 6.8 million deaths annually. Heparan sulfate proteoglycans (HSPGs) are complex extracellular molecules implicated in promoting Tau fibril formation resulting in Tau tangles, a hallmark of Alzheimer's disease (AD). HSPG-Tau protein interactions contribute to various AD stages via aggregation, toxicity, and clearance, largely via interactions with the glypican 1 and syndecan 3 core proteins. The tunnelling nanotubes (TNTs) pathway is emerging as a facilitator of intercellular molecule transport, including Tau and Amyloid β proteins, across extensive distances. While current TNT-associated evidence primarily stems from cancer models, their role in Tau propagation and its effects on recipient cells remain unclear. This review explores the interplay of TNTs, HSPGs, and AD-related factors and proposes that HSPGs influence TNT formation in neurodegenerative conditions such as AD.

Keywords: Alzheimer's disease; Aβ; Heparan sulfate proteoglycans; Neurological disorders; P-tau; Tau; Tunnelling nanotubes.

Publication types

Review