Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3 | Zendy

Xiaobo Mao | Zendy; Michael T. Ou | Zendy; Senthilkumar S. Karuppagounder | Zendy; TaeIn Kam | Zendy; Xiling Yin | Zendy; Yulan Xiong | Zendy; Preston Ge | Zendy; George K. E. Umanah | Zendy; Saurav Brahmachari | Zendy; JooHo Shin | Zendy; Ho Chul Kang | Zendy; Jianmin Zhang | Zendy; Jinchong Xu | Zendy; Rong Chen | Zendy; Hyejin Park | Zendy; Shaida A. Andrabi | Zendy; Sung Ung Kang | Zendy; Rafaella A. Gonçalves | Zendy; Yu Liang | Zendy; Shu Zhang | Zendy; Chen Qi | Zendy; Sharon Lam | Zendy; James A. Keiler | Zendy; Joel Tyson | Zendy; Donghoon Kim | Zendy; Nikhil Panicker | Zendy; Seung Pil Yun | Zendy; Creg J. Workman | Zendy; Dario A.A. Vignali | Zendy; Valina L. Dawson | Zendy; Han Seok Ko | Zendy; Ted M. Dawson | Zendy

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Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3

Author(s) -

Xiaobo Mao,

Michael T. Ou,

Senthilkumar S. Karuppagounder,

TaeIn Kam,

Xiling Yin,

Yulan Xiong,

Preston Ge,

George K. E. Umanah,

Saurav Brahmachari,

JooHo Shin,

Ho Chul Kang,

Jianmin Zhang,

Jinchong Xu,

Rong Chen,

Hyejin Park,

Shaida A. Andrabi,

Sung Ung Kang,

Rafaella A. Gonçalves,

Yu Liang,

Shu Zhang,

Chen Qi,

Sharon Lam,

James A. Keiler,

Joel Tyson,

Donghoon Kim,

Nikhil Panicker,

Seung Pil Yun,

Creg J. Workman,

Dario A.A. Vignali,

Valina L. Dawson,

Han Seok Ko,

Ted M. Dawson

Publication year - 2016

Publication title -

science

Language(s) - Uncategorized

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.aah3374

Subject(s) - substantia nigra , pars compacta , alpha synuclein , biology , microbiology and biotechnology , neuroscience , lewy body , parkinson's disease , pathology , dopamine , medicine , disease , dopaminergic

Emerging evidence indicates that the pathogenesis of Parkinson's disease (PD) may be due to cell-to-cell transmission of misfolded preformed fibrils (PFF) of α-synuclein (α-syn). The mechanism by which α-syn PFF spreads from neuron to neuron is not known. Here, we show that LAG3 (lymphocyte-activation gene 3) binds α-syn PFF with high affinity (dissociation constant = 77 nanomolar), whereas the α-syn monomer exhibited minimal binding. α-Syn-biotin PFF binding to LAG3 initiated α-syn PFF endocytosis, transmission, and toxicity. Lack of LAG3 substantially delayed α-syn PFF-induced loss of dopamine neurons, as well as biochemical and behavioral deficits in vivo. The identification of LAG3 as a receptor that binds α-syn PFF provides a target for developing therapeutics designed to slow the progression of PD and related α-synucleinopathies.

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