Amyloid-β interrupts canonical Sonic hedgehog signaling by distorting primary cilia structure

Cilia
Anna G Vorobyeva, Aleister J Saunders

Abstract

Primary cilia are small non-motile microtubule and cell membrane protrusions expressed on most vertebrate cells, including cortical and hippocampal neurons. These small organelles serve as sensory structures sampling the extracellular environment and reprogramming the transcriptional machinery in response to environmental change. Primary cilia are decorated with a variety of receptor proteins and are necessary for specific signaling cascades such as the Sonic hedgehog (Shh) pathway. Disrupting cilia structure or function results in a spectrum of diseases collectively referred to as ciliopathies. Common to human ciliopathies is cognitive impairment, a symptom also observed in Alzheimer's disease (AD). One hallmark of AD is accumulation of senile plaques composed of neurotoxic Amyloid-β (Aβ) peptide. The Aβ peptide is generated by the proteolytic cleavage of the amyloid precursor protein (APP). We set out to determine if Aβ affects primary cilia structure and the Shh signaling cascade. We utilized in vitro cell-based assays in combination with fluorescent confocal microscopy to address our study goals. Shh signaling and cilia structure was studied using two different cell lines, mouse NIH3T3 and human HeLa cells. To investigate h...Continue Reading

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Citations

Feb 14, 2019·Annals of the New York Academy of Sciences·Mayuri ShuklaRussel J Reiter
May 28, 2019·Andrology·Laura GirardetClémence Belleannée
Nov 30, 2019·Frontiers in Genetics·Noriaki SasaiToru Kondo
Jan 11, 2020·Frontiers in Cellular Neuroscience·Rasem MustafaRosanna Parlato
Nov 19, 2020·Cellular and Molecular Neurobiology·Saloni Rahi, Sidharth Mehan
Mar 28, 2021·Pharmacology & Therapeutics·Max Duong PhuMelanie Philipp
Oct 13, 2021·Communications Biology·Hikari TanakaHitoshi Okazawa

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Methods Mentioned

BETA
Transfection
Fluorescence
transgenic

Software Mentioned

Volocity Image
Volocity
Volocity 3D

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