Format

Send to

Choose Destination
Neuropathology. 2015 Oct;35(5):432-40. doi: 10.1111/neup.12204. Epub 2015 May 7.

Isopentenyl diphosphate isomerase, a cholesterol synthesizing enzyme, is localized in Lewy bodies.

Author information

1
Department of Neuropathology, Hirosaki University Graduate School of Medicine, Hirosaki.
2
Department of Neurology and Neurobiology of Ageing, Kanazawa University Graduate School of Medical Science, Kanazawa.
3
Department of Pathological Neuroscience, Center for Bioresource-based Researches.
4
Department of Pathology, Brain Research Institute, University of Niigata, Niigata.
5
Department of Neurology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Abstract

Isopentenyl diphosphate isomerase (IDI) is a cytoplasmic enzyme involved in the biosynthesis of isoprenoids including cholesterols. IDI has two isoforms in humans: IDI1 and IDI2. Since lipids are known to be a component of Lewy bodies (LBs), we investigated the immunohistochemical localization of IDI1 and IDI2 in the brain of patients with LB disease and multiple system atrophy (MSA) and normal control subjects. In normal controls, the cytoplasm of neurons was weakly immunostained with anti-IDI1 and anti-IDI2 antibodies throughout the nervous system. In LB disease, brainstem-type LBs were strongly positive for IDI1 and IDI2, and cortical LBs were unstained or barely immunolabeled. Double immunofluorescence staining revealed co-localization of phosphorylated α-synuclein with IDI1 or IDI2. Glial cytoplasmic inclusions in MSA were unstained. Previous studies have shown that levels of cholesterol metabolites are increased in the cerebral cortex of patients with LB disease, and that these metabolites accelerate α-synuclein aggregation. The present findings suggest that IDI1 and IDI2 may be associated with the production of cholesterol metabolites in neurons, leading to α-synuclein aggregation during the process of LB formation.

KEYWORDS:

Lewy body; Parkinson's disease; cholesterol; isopentenyl diphosphate isomerase; α-synuclein

PMID:
25950736
DOI:
10.1111/neup.12204
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center