The couple of netrin-1/α-Synuclein regulates the survival of dopaminergic neurons via α-Synuclein disaggregation

被引：7
作者：
Kang, Eun Ji [1 ]
Jang, Seung Min [1 ]
Lee, Ye Ji [1 ]
Jeong, Ye Ji [1 ]
Kim, You Jin [1 ]
Kang, Seong Su [2 ]
Ahn, Eun Hee [1 ]
机构：
[1] Hallym Univ, Coll Med, Dept Physiol, Chunchon 24252, South Korea
[2] Emory Univ, Dept Pathol & Lab Med, Sch Med, Atlanta, GA 30322 USA
来源：
BMB REPORTS | 2023年 / 56卷 / 02期
基金：
新加坡国家研究基金会;
关键词：
alpha-synuclein; Dopaminergic neuron; Molecule-molecule interaction; Netrin-1; Parkinson's disease; PARKINSONS-DISEASE; PROTEIN; NETRIN-1; PHOSPHORYLATION; EXPRESSION;
D O I：
10.5483/BMBRep.2023-0004
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The abnormal accumulation and aggregation of the misfolded a-synuclein protein is the neuropathological hallmark of all a-synucleinopathies, including Parkinson's disease. The secreted proteins known as netrins (netrin-1, netrin-3, and netrin-4) are related to laminin and have a role in the molecular pathway for axon guidance and cell survival. Interestingly, only netrin-1 is sig-nificantly expressed in the substantia nigra (SN) of healthy adult brains and its expression inversely correlates with that of a-syn-uclein, which prompted us to look into the role of a-synuclein and netrin-1 molecular interaction in the future of dopaminergic neurons. Here, we showed that netrin-1 and a-synuclein directly interacted in pre-formed fibrils (PFFs) generation test, real time binding assay, and co-immunoprecipitation with neurotoxin treated cell lysates. Netrin-1 deficiency appeared to activate the dopaminergic neuronal cell death signal pathway via a-synuclein aggregation and hyperphosphorylation of a-synuclein S129. Taken together, netrin-1 can be a promising therapeutic molecule in Parkinson's disease.
引用
收藏
页码：126 / 131
页数：6
相关论文
共 27 条
[1]   BDNF and Netrin-1 repression by C/EBPβ in the gut triggers Parkinson's disease pathologies, associated with constipation and motor dysfunctions [J].
Ahn, Eun Hee ;
Kang, Seong Su ;
Liu, Xia ;
Cao, Xuebing ;
Choi, Soo Young ;
Musazzi, Laura ;
Mehlen, Patrick ;
Ye, Keqiang .
PROGRESS IN NEUROBIOLOGY, 2021, 198
[2]   Initiation of Parkinson's disease from gut to brain by δ-secretase [J].
Ahn, Eun Hee ;
Kang, Seong Su ;
Liu, Xia ;
Chen, Guiqin ;
Zhang, Zhentao ;
Chandrasekharan, Bindu ;
Alam, Ashfaqul M. ;
Neish, Andrew S. ;
Cao, Xuebing ;
Ye, Keqiang .
CELL RESEARCH, 2020, 30 (01) :70-87
[3]   Phosphorylation of Ser-129 is the dominant pathological modification of α-synuclein in familial and sporadic Lewy body disease [J].
Anderson, John P. ;
Walker, Donald E. ;
Goldstein, Jason M. ;
de laat, Rian ;
Banducci, Kelly ;
Caccavello, Russell J. ;
Barbour, Robin ;
Huang, Jiping ;
Kling, Kristin ;
Lee, Michael ;
Diep, Linnea ;
Keim, Pamela S. ;
Shen, Xiaofeng ;
Chataway, Tim ;
Schlossmacher, Michael G. ;
Seubert, Peter ;
Schenk, Dale ;
Sinha, Sukanto ;
Gai, Wei Ping ;
Chilcote, Tamie J. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (40) :29739-29752
[4]   Diagnosis and Treatment of Parkinson Disease A Review [J].
Armstrong, Melissa J. ;
Okun, Michael S. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2020, 323 (06) :548-560
[5]   Brain-derived neurotrophic factor and its clinical implications [J].
Bathina, Siresha ;
Das, Undurti N. .
ARCHIVES OF MEDICAL SCIENCE, 2015, 11 (06) :1164-1178
[6]   Parkinson's disease: animal models and dopaminergic cell vulnerability [J].
Blesa, Javier ;
Przedborski, Serge .
FRONTIERS IN NEUROANATOMY, 2014, 8
[7]   Performance and Its Limits in Rigid Body Protein-Protein Docking [J].
Desta, Israel T. ;
Porter, Kathryn A. ;
Xia, Bing ;
Kozakov, Dima ;
Vajda, Sandor .
STRUCTURE, 2020, 28 (09) :1071-+
[8]   Reduced BDNF mRNA expression in the Parkinson's disease substantia nigra [J].
Howells, DW ;
Porritt, MJ ;
Wong, JYF ;
Batchelor, PE ;
Kalnins, R ;
Hughes, AJ ;
Donnan, GA .
EXPERIMENTAL NEUROLOGY, 2000, 166 (01) :127-135
[9]   Netrin-1 and its receptor DCC modulate survival and death of dopamine neurons and Parkinson's disease features [J].
Jasmin, Melissa ;
Ahn, Eun Hee ;
Voutilainen, Merja H. ;
Fombonne, Joanna ;
Guix, Catherine ;
Viljakainen, Tuulikki ;
Kang, Seong Su ;
Yu, Li-ying ;
Saarma, Mart ;
Mehlen, Patrick ;
Ye, Keqiang .
EMBO JOURNAL, 2021, 40 (03)
[10]   α-Synuclein stimulation of monoamine oxidase-B and legumain protease mediates the pathology of Parkinson's disease [J].
Kang, Seong Su ;
Ahn, Eun Hee ;
Zhang, Zhentao ;
Liu, Xia ;
Manfredsson, Fredric P. ;
Sandoval, Ivette M. ;
Dhakal, Susov ;
Iuvone, P. Michael ;
Cao, Xuebing ;
Ye, Keqiang .
EMBO JOURNAL, 2018, 37 (12)
123