Affiliations: Molecular Neurology Program, Huntington Medical
Research Institutes, 99 North El Molino Avenue, Pasadena, CA 91101, USA. Tel.:
+1 626 795 4343 | Thermo Electron, 355 River Oaks Parkway, San Jose, CA
95134, USA. Tel.: +1 408 965 6285
Abstract: Glutathione independent prostaglandin D synthase (Swissprot P41222,
PTGDS) has been identified in human cerebrospinal fluid and some changes in
PTGDS in relation to disease have been reported. However, little is known of
the extent that PTGDS isoforms fluctuate across a large range of congenital and
acquired diseases. The purpose of this study was to examine changes in PTGDS
isoforms in such a population. Spinal fluid from 22 healthy study participants
(normal controls) with no classifiable neurological or psychiatric diagnosis
was obtained and PTGDS isoforms were identified by specific immunostaining and
mass spectrometry after denaturing 2D gel electrophoresis. The PTGDS isoforms
in controls consisted of five charge isoforms that were always present and a
small number of occasional, low abundance isoforms. A qualitative survey of 98
different people with a wide range of congenital and acquired diseases revealed
striking changes. Loss of the control isoforms occurred in congenital
malformations of the nervous system. Gain of additional isoforms occurred in
some degenerative, most demyelinating and vasculitic diseases, as well as in
Creutzfeldt-Jakob disease. A retrospective analysis of published data that
quantified relative amounts of PTGDS in multiple sclerosis, schizophrenia and
Parkinson's disease compared to controls revealed significant dysregulation. It
is concluded that qualitative and quantitative fluctuations of cerebrospinal
fluid PTGDS isoforms reflect both major and subtle brain pathophysiology.
