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New Therapeutic Targets for Parkinson’s Disease

EVENT: 
Weekly Seminar | Not Open to the Public
Who Should Attend: 
Researchers

Speakers

Han Seok Ko, Ph.D.
Associate Professor - Department of Neurology
Neuroregeneration and Stem Cell Programs - Institute for Cell Engineering

Abstract 

My work has been focused on the elucidation of key molecular pathways in the pathogenesis of Parkinson’s disease and the development of new agents to treat Parkinson’s disease and related α-synculeinopathy. New targets include c-Abl, LAG3, and GLP-1R. 1. c-Abl: We have defined a critical role of c-Abl activation in α-synucleininduced neurodegeneration and demonstrated that selective inhibition of c-Abl is sufficient for neuroprotection. We have been investigating potentially safer and more effective c-Abl inhibitor drug options in mouse models of PD. 2. Lymphocyte-Activation Gene 3 (LAG3): We have elucidated the molecular mechanisms of prionlike cell-to-cell transmission of misfolded α-synuclein in the brain of Parkinson’s disease. We have identified lymphocyte-activation gene 3 (LAG3) as a misfolded α-synuclein preformed fibrils (PFF) transmission receptor. 3. New Glucagon-like peptide-1 (GLP-1) agonist: We have shown that a potent, brain penetrant long acting GLP-1R agonist NLY01 protects against the loss of dopamine neurons and behavioral deficits in the α-synuclein preformed fibril model of sporadic PD. NLY01 also prolongs the life and reduces the behavioral deficits and neuropathological abnormalities in the human A53T α-synuclein (hA53T) transgenic (Tg) model of α-synucleinopathy induced neurodegeneration. We have found that NLY01 is a potent GLP-1R agonist with favorable properties that is neuroprotective via the direct prevention of microglial mediated conversion of astrocytes to an A1 neurotoxic phenotype.

Han Seok Ko, Ph.D. Figure

Publications

Kim D, Yoo JM, Hwang H, Lee J, Lee SH, Yun SP, Park MJ, Lee M, Choi S, Kwon SH, Lee S, Kwon SH, Kim S, Park YJ, Kinoshita M, Lee YH, Shin S, Paik SR, Lee SJ, Lee S, Hong BH, Ko HS
Graphene quantum dots prevent α-synucleinopathy in Parkinson's disease.
Nat Nanotechnol. 2018 Sep;13(9):812-818. doi: 10.1038/s41565-018-0179-y. Epub 2018 Jul 9.
Yun SP, Kam TI, Panicker N, Kim S, Oh Y, Park JS, Kwon SH, Park YJ, Karuppagounder SS, Park H, Kim S, Oh N, Kim NA, Lee S, Brahmachari S, Mao X, Lee JH, Kumar M, An D, Kang SU, Lee Y, Lee KC, Na DH, Kim D, Lee SH, Roschke VV, Liddelow SA, Mari Z, Barres BA, Dawson VL, Lee S, Dawson TM, Ko HS
Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson's disease.
Nat Med. 2018 Jul;24(7):931-938. doi: 10.1038/s41591-018-0051-5. Epub 2018 Jun 11.
Mao X, Ou MT, Karuppagounder SS, Kam TI, Yin X, Xiong Y, Ge P, Umanah GE, Brahmachari S, Shin JH, Kang HC, Zhang J, Xu J, Chen R, Park H, Andrabi SA, Kang SU, Gonçalves RA, Liang Y, Zhang S, Qi C, Lam S, Keiler JA, Tyson J, Kim D, Panicker N, Yun SP, Workman CJ, Vignali DA, Dawson VL, Ko HS, Dawson TM.
Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3.
Science. 2016 Sep 30;353(6307). pii: aah3374.

When

Tuesday, April 30, 2019 - 12:30pm

Where

785 Mamaroneck Avenue
White Plains, NY 10605
United States
Conference Room: 
Billings Building – Rosedale

More Information

Lindsey Echevarria

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