Protein dynamics-based control of proteotoxicity in neurodegenerative diseases
S. B. Lee (Convener)
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AbstractWith increasing life expectancy, neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Huntington’s disease (HD), have become one of the major threats to humans. Although the symptoms vary depending on the type of disease, these neurodegenerative diseases share protein toxicity as one of their key pathogenic mechanisms. Herein protein toxicity is defined as all the pathological changes that ensue from accumulation, mis-localization, and/or oligomerization of disease-associated toxic proteins such as α-synuclein in PD, polyglutamine (polyQ)-containing proteins in polyQ diseases (e.g., HD), and dipeptide repeat proteins and TDP-43 in ALS. Conventional understanding of protein toxicity is that protein toxicity simply reflects the amount of accumulated toxic proteins. For this reason, our challenges done so far against protein toxicity have been based on a simple strategy of reducing the amount of toxic proteins. However, the exact nature of protein toxicity appears to be much more complex than we have conceived, and thus new paradigm for understanding protein toxicity is highly demanded. In this talk, I will present our current efforts to understand exact nature of proteotoxicity in neurodegenerative diseases and potential solutions that can effectively control proteotoxicity, named as protein dynamics-based control of proteotoxicity. I will tell you about our recent study unveiling cellular intrinsic mechanisms regulating nucleocytoplasmic transport of TDP-43 in neurons.Keywords: protein toxicity, neurodegenerative diseases
S. B. Lee (Convener) (2022). Protein dynamics-based control of proteotoxicity in neurodegenerative diseases. Gerontechnology, 21(s),1-1
https://doi.org/10.4017/gt.2022.21.s.808.sp3