HYBRID EVENT: You can participate in person at London, UK or Virtually from your home or work.

3rd Edition of International Conference on Tissue Engineering and Regenerative Medicine

August 21-23, 2023

August 21 -23, 2023 | London, UK
TERM C 2022

Xiaobo Mao

Xiaobo Mao, Speaker at TERM C conferences 2022
Johns Hopkins University School of Medicine, United States
Title : Pathogenic Alpha-synuclein cell-to-cell transmission mechanism and related therapeutic development

Abstract:

α-Synucleinopathies is characterized with accumulation of misfolded α-synuclein (α-syn), including Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB), and Multiple System Atrophy (MSA). Emerging evidence indicates that pathogenesis of α-synucleinopathies may be due to cell-to-cell transmission of prion-like preformed fibrils (PFF) of α-syn. We identified several receptors (Lag3, Aplp1, neurexins) that specifically bind with α-syn fibrils but not α-syn monomer. Lymphocyte-activation gene-3 (Lag3) exhibits the highest binding affinity with α-syn fibrils, and α-syn fibrils binding to Lag3 initiated pathogenic α-syn endocytosis, propagation, transmission, and toxicity. Lack of Lag3 (Lag3-/-) and anti-Lag3 can substantially delay α-syn PFF-induced loss of dopamine neurons, as well as biochemical and behavioral deficits in vivo. The identification of Lag3 that binds α-syn PFF provides a target for developing therapeutics designed to slow the progression of PD and related α-synucleinopathies. Biocompatible antioxidant nanozyme, PtCu nanoalloys (NAs), is applied to fight against α-syn spreading. The results show that PtCu NAs significantly inhibit α-syn pathology, cell death, and neuron-to-neuron transmission by scavenging reactive oxygen species (ROS) in primary neuron cultures. Moreover, the PtCu NAs significantly inhibit α-syn spreading induced by intrastriatal injection of PFF. It is the first time to observe nanozyme can block prion-like spreading, which provides a proof of concept for nanozyme therapy.

Biography:

Dr. Mao received his PhD (Physical Chemistry) at the National Center for Nanoscience and Technology, Chinese Academy of Sciences in 2010. He then worked as postdoc in the labs of Profs. Drs. Ted and Valina Dawson at the Institute for Cell Engineering, Department of Neurology, Johns Hopkins School of Medicine (JHSOM) during 2010-2016. After postdoctoral fellowship, he worked as Assistant Professor in 2017 and became Associate Professor in 2021 at JHSOM. He has published more than 50 research articles in many high-impact journals (Science, Nature, Nature Medicine, PNAS, Nature Comm, Nano Today) focusing on pathogenic protein cell-to-cell spreading.

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