Abstract
The cellular polyamines putrescine, spermidine, and spermine accelerate the aggregation and fibrillization of alpha-synuclein, the major protein component of Lewy bodies associated with Parkinson's disease. Circular dichroism and fluorometric thioflavin T kinetic studies showed a transition of alpha-synuclein from unaggregated to highly aggregated states, characterized by lag and transition phases. In the presence of polyamines, both the lag and transition times were significantly shorter. All three polyamines accelerated the aggregation and fibrillization of alpha-synuclein to a degree that increased with the total charge, length, and concentration of the polyamine. Electron and scanning force microscopy of the reaction products after the lag phase revealed the presence of aggregated particles (protofibrils) and small fibrils. At the end of the transition phase, alpha-synuclein formed long fibrils in all cases, although some morphological variations were apparent. In the presence of polyamines, fibrils formed large networks leading ultimately to condensed aggregates. In the absence of polyamines, fibrils were mostly isolated. We conclude that the polyamines at physiological concentrations can modulate the propensity of alpha-synuclein to form fibrils and may hence play a role in the formation of cytosolic alpha-synuclein aggregates.
Highlights
The approximately 15 a- and 15 .8-tubulin genes of Trypanosoma brucei are arranged in a tandem array of alternating a- and f3-tubulin genes
We have examined transcripts from the T. brucei tubulin gene family
We report that this spliced leader (SL)-like sequence is transcribed and that,B-tubulin as well as a-tubulin transcripts are recipients of an authentic SL identical to that found on the 5' ends of variant surface glycoprotein (VSG) mRNAs
Summary
The approximately 15 a- and 15 .8-tubulin genes of Trypanosoma brucei are arranged in a tandem array of alternating a- and f3-tubulin genes. A common short leader sequence of 35 nucleotides is found at the 5' terminus of many, and perhaps all, mRNAs in trypanosomes [1,2,3,4] This spliced leader (SL) [5] sequence of Trypanosoma brucei appears to originate from a 1.4-kilobase (kb) DNA sequence that is present in '200 copies per genome [5, 6]. A small RNA species transcribed from the SL genes and containing a SL on its 5' end has been identified from T. brucei, T. cruzi, and L. collosoma and is the best candidate to serve as a SL donor [10,11,12] In this investigation, we have examined transcripts from the T. brucei tubulin gene family. This article must be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact
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