Yi-Yang Liu
Senior student in DBT at NYCU
Research interest: The abnormality observed in ALS dermal fibroblasts
Zhi-Tian Kuo
Graduate student in BME at NYCU
Research interest: Biomaterial
Ching Lee
Graduate student in DBT at NYCU
Research interest: The role of dysregulated microtubules in ALS.
Studying the role of hyperdynamic microtubules in amyotrophic lateral sclerosis: from the perspectives of neurons and dermal fibroblasts
Yi-Yang Liu (劉怡揚) 1 , Zhi-Tian Kuo (郭至恬) 2 , Ching Lee (李擎) 1 , Eric Hwang 1,2,3,4
1 Department of Biological Science & Technology, National Yang Ming Chiao Tung University 2 Institute of Biomedical Engineering, National Yang Ming Chiao Tung University 3 Institute of Molecular Medicine and Bioengineering, National Yang Ming Chiao Tung University 4 Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive loss of motor neurons. While the exact mechanisms underlying the development and progression of ALS are not fully understood, recent studies have revealed new insights into the pathogenesis of ALS. These include the cortical hyperexcitability, axonal transport impairment, and nucleocytoplasmic transport defects. Recent data suggest that microtubule (MT) dynamic dysregulation is at core of all the aforementioned pathomechanisms. MTs are dynamic biopolymers made of heterodimers of α- and β-tubulin. MT plus-ends polymerize and depolymerize rapidly through the addition and removal of tubulin heterodimers and switch between these two phases frequently, these properties make them the dynamic cytoskeletons. MTs are considered “hyperdynamic” when tubulin heterodimers are actively exchanging between the polymeric and the cytosolic pools. This manifests as MTs actively growing or shrinking and spending very little time in the “pause” phase. In contrast, tubulin heterodimers show limited exchange between the polymeric and the cytosolic pools when MTs are “hypodynamic”. It has been discovered that MTs become hyperdynamic in spinal cords and motor nerves isolated from ALS mice. Congruently, hyperdynamic MTs have been detected in motor neurons in vivo using 2-photon microscopy in ALS mice. Another evidence comes from the observation that the ALS-causing SOD1G93A protein but not wild-type SOD1 protein interacts with tubulin heterodimers and influences the polymerization dynamics of MTs in vitro. Here we are presenting data showing the effect of cortical hyperexcitability on microtubule dynamics and the effect of microtubule dynamic dysregulation on nucleocytoplasmic transport. Additionally, microtubule dynamic dysregulation will be examined in dermal fibroblasts of the skin, which have been shown to exhibits a variety of phenotypes including the delayed return phenomenon and collagen abnormality.