Regulation of in vitro fibril formation of synuclein mutant proteins by Hsp104p.
Hsp104p, as an anti-oxidative protector of ROS generation, was examined to inquire if it prevents aggregation of synuclein mutants, A30P or A53T upon aging, in vitro. The role of Hsp104p was also addressed in dissociation of pre-formed aggregates of synuclein mutants. Significant protection in fibril formation was observed by wild-type Hsp104p regardless of ATP presence, not by mutant Hsp104p. To a lesser extent, the dissociation effect of wild-type Hsp104p was observed only in the presence of ATP. These results will be discussed in relation to the development of an antioxidant approach to prevent amyloid fibril formation in several neurodegenerative diseases.
Kong
Byungmoon
B
Department of Applied Chemistry and Recombinant Protein Expression Center, Sejong University, 98 Gunja-Dong, Gwangjin-Gu, Seoul 143-747, South Korea.
Chae
Young Kee
YK
Lee
Kyunghee
K
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D000975:Antioxidants / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000494:pharmacology*; D051843:Synucleins
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D006360:Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D051843:Synucleins; C070972:HsP104 protein, S cerevisiae; D000255:Adenosine Triphosphate