Skip to main content

A Novel Platform for Neurodegenerative Disease Studies: Applying Photocontrollable Probe to Induce Pathological Proteins into Amyloid Fibers in Live Cells
研究神經退化性疾病的新平台: 以光控探針誘發致病蛋白在活體細胞形成類澱粉纖維堆積

The breakthrough in the neurodegenerative disease diagnosis: Applying photocontrollable probe to precisely monitor disease progression

Despite hyperphosphorylated TDP-43 has been confirmed as one of the major components in the inclusion bodies of patients with Amyotrophic Lateral Sclerosis (ALS) or Frontotemporal lobar degeneration (FTLD), the underlying disease mechanism has not yet been fully elucidated. Dr. Joseph Jen-Tse Huang, an associate research fellow at the Institute of Chemistry in Academia Sinica, Dr. Hsien-Ming Lee, an assistant research fellow at the Institute of Chemistry in Academia Sinica, and Dr. Eric Hwang, an associate professor at Department of Biological Science and Technology in National Chiao Tung University, developed a photocontrollable probe to induce TDP-43 aggregates in live cells. This platform enables researchers to spatiotemporally control the formation of the neurotoxic fibrils and directly observe the TDP-43 amyloidogenic process. The research was published in ACS Nano on June 27th, 2017.

Dr. Joseph Jen-Tse Huang was the first to discover the specific TDP-43 C-terminal peptide was able to form amyloid fibers and published his research findings in Journal of American Chemical Society (JACS) in 2010. Later on, he further identified the amyloidogenic core sequence of TDP-43. Based on these findings, Dr. Huang and his collaborators developed a fluorescence-labeled, membrane-permeable, photocontrollable probe which can spatiotemporally controlled the formation of endogenous TDP-43 aggregation in the cytosol and impaired the nuclearcytoplasmic transport without using laborious microinjection. In addition, this probe induced TDP-43 aggregation subsequently triggered neuron degeneration and neurite fragmentation. The observed phenomenon indicated that this probe can be applied as a model platform to mimic the pathological phenotype of neuron in neurodegenerative disease.

Dr. Huang remarked that “Within many currently developed photochemical toolboxes, light would be one of the best triggers to initiate and directly observe the process of TDP-43 amyloidogenesis in vivo. This platform can be widely applied in the studies of aggregation-induced protein mislocalization, amyloid-induced pathogenesis, and protein misfolding in neurodegenerative diseases.” The related results are now under patent application.

In addition, Dr. Huang also collaborated with other principal investigators from Academia Sinica, National Yang-Ming University, and Taipei Veterans General Hospital to extend the use of this platform. In the future, the research team aims to apply the photocontrollable probe both in basic research and clinical science in ALS and other neurodegenerative diseases.

The full article entitled “Photocontrollable Probe Spatiotemporally Induces Neurotoxic Fibrillar Aggregates and Impairs Nucleocytoplasmic Trafficking” can be found at the ACS NANO website at:

Media Contact:
Dr. Joseph Jen-Tse Huang, Associated Research Fellow, Institute of Chemistry, Academia Sinica
(Tel) +886-2-2789-8652


肌萎縮性脊髓側索硬化症(又稱為漸凍人症; ALS)及相關神經元退化性疾病已被發現及研究了多年,但是目前研究與醫療人員對於此類疾病的早期診斷及治療依舊束手無策。雖然近年來高度磷酸化的TDP-43蛋白已被證實為ALS中包涵體的主要成分,此蛋白在致病機轉中所扮演的角色卻仍然不明。本院化學研究所黃人則副研究員,偕同化學所李賢明助研究員,以及交通大學生物科技系黃兆祺副教授,組成研究團隊共同合作,利用化學生物學的技術,建構出可以在活體細胞中誘發TDP-43蛋白異常聚集的光控探針。此探針不但可以控制聚集體產生的時間和位置,並可以直接觀察受光誘發的TDP-43蛋白澱粉狀纖維化過程,便於找出致病的機制。這項研究成果於2017年6月27日刊登在《美國化學會奈米》(ACS Nano)。






(Tel) +886-2-2789-8652