TY - JOUR
T1 - Recent advances in α-synuclein functions, advanced glycation, and toxicity
T2 - implications for Parkinson's disease.
AU - Guerrero, Erika
AU - Vasudevaraju, P.
AU - Hegde, Muralidhar L.
AU - Britton, G. B.
AU - Rao, K. S.
N1 - Funding Information:
The authors wish to thank Mr. Arturo Melo for supporting the research through Melo Brain Grant, Republic of Panama.
PY - 2013/4
Y1 - 2013/4
N2 - The toxicity of α-synuclein in the neuropathology of Parkinson's disease which includes its hallmark aggregation has been studied scrupulously in the last decade. Although little is known regarding the normal functions of α-synuclein, its association with membrane phospholipids suggests its potential role in signaling pathways. Following extensive evidences for its nuclear localization, we and others recently demonstrated DNA binding activity of α-synuclein that modulates its conformation as well as aggregation properties. Furthermore, we also underscored the similarities among various amyloidogenic proteins involved in neurodegenerative diseases including amyloid beta peptides and tau. Our more recent studies show that α-synuclein is glycated and glycosylated both in vitro and in neurons, significantly affecting its folding, oligomeric, and DNA binding properties. Glycated α-synuclein causes increased genome damage both via its direct interaction with DNA and by increased generation of reactive oxygen species as glycation byproduct. In this review, we discuss the mechanisms of glycation and other posttranslational modifications of α-synuclein, including phosphorylation and nitration, and their role in neuronal death in Parkinson's disease.
AB - The toxicity of α-synuclein in the neuropathology of Parkinson's disease which includes its hallmark aggregation has been studied scrupulously in the last decade. Although little is known regarding the normal functions of α-synuclein, its association with membrane phospholipids suggests its potential role in signaling pathways. Following extensive evidences for its nuclear localization, we and others recently demonstrated DNA binding activity of α-synuclein that modulates its conformation as well as aggregation properties. Furthermore, we also underscored the similarities among various amyloidogenic proteins involved in neurodegenerative diseases including amyloid beta peptides and tau. Our more recent studies show that α-synuclein is glycated and glycosylated both in vitro and in neurons, significantly affecting its folding, oligomeric, and DNA binding properties. Glycated α-synuclein causes increased genome damage both via its direct interaction with DNA and by increased generation of reactive oxygen species as glycation byproduct. In this review, we discuss the mechanisms of glycation and other posttranslational modifications of α-synuclein, including phosphorylation and nitration, and their role in neuronal death in Parkinson's disease.
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U2 - 10.1007/s12035-012-8328-z
DO - 10.1007/s12035-012-8328-z
M3 - Review article
C2 - 22923367
AN - SCOPUS:84885468645
SN - 0893-7648
VL - 47
SP - 525
EP - 536
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 2
ER -