In:
Brain Pathology, Wiley, Vol. 25, No. 5 ( 2015-09), p. 552-564
Abstract:
In L ewy body disease ( LBD ) such as dementia with LBs and P arkinson's disease, several lines of evidence show that disrupted proteolysis occurs. p 62/ SQSTM 1 ( p 62) is highly involved with intracellular proteolysis and is a component of ubiquitin‐positive inclusions in various neurodegenerative disorders. However, it is not clear whether p 62 deficiency affects inclusion formation and abnormal protein accumulation. To answer this question, we used a mouse model of LBD that lacks p 62, and found that LB ‐like inclusions were observed in transgenic mice that overexpressed α‐synuclein ( T g mice) with or without the p 62 protein. p 62 deficiency enhanced α‐synuclein pathology with regard to the number of inclusions and staining intensity compared with T g mice that expressed p 62. To further investigate the molecular mechanisms associated with the loss of p 62 in T g mice, we assessed the mRNA and protein levels of several molecules, and found that the neighbor of the brca1 gene ( NB r1 ), which is functionally and structurally similar to p 62, is increased in T g mice without p 62 compared with control T g mice. These findings suggest that p 62 and NBR 1 affect the pathogenesis of neurodegenerative diseases through the cooperative modulation of α‐synuclein aggregation.
Type of Medium:
Online Resource
ISSN:
1015-6305
,
1750-3639
DOI:
10.1111/bpa.2015.25.issue-5
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2029927-8
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