PMID- 25233404
OWN - NLM
STAT- MEDLINE
DCOM- 20150605
LR  - 20180101
IS  - 1470-8752 (Electronic)
IS  - 0300-5127 (Linking)
VI  - 42
IP  - 5
DP  - 2014 Oct
TI  - Astrocytosis in infantile neuronal ceroid lipofuscinosis: friend or foe?
PG  - 1282-5
LID - 10.1042/BST20140188 [doi]
AB  - Infantile neuronal ceroid lipofuscinosis (INCL; infantile Batten disease) is an 
      inherited paediatric neurodegenerative disease. INCL is caused by a deficiency in 
      the lysosomal enzyme palmitoyl-protein thioesterase-1 (PPT1) and is thus 
      classified as a lysosomal storage disease. Pathological examination of both human 
      and murine INCL brains reveals progressive, widespread neuroinflammation. In 
      fact, astrocyte activation appears to be the first histological sign of disease. 
      However, the role of astrocytosis in INCL was poorly understood. The hallmark of 
      astrocyte activation is the up-regulation of intermediate filaments, such as 
      glial fibrillary acidic protein (GFAP) and vimentin. The role of astrocytosis in 
      INCL was studied in a murine model lacking PPT1 and the intermediate filaments 
      GFAP and vimentin (triple-knockout). This murine model of INCL with attenuated 
      astrocytosis had an exacerbated pathological and clinical phenotype. The 
      triple-knockout mouse had a significantly shortened lifespan, and accelerated 
      cellular and humoural neuroinflammatory response compared with the parental 
      PPT1(-/-) mouse. The data obtained from the triple-knockout mouse strongly 
      suggest that astrocyte activation plays a beneficial role in early INCL disease 
      progression. A more thorough understanding of the glial responses to lysosomal 
      enzyme deficiencies and the accumulation of undergraded substrates will be 
      crucial to developing effective therapeutics.
FAU - Shyng, Charles
AU  - Shyng C
AD  - *Department of Medicine, Washington University School of Medicine, 660 South 
      Euclid Avenue, St. Louis, MO 63110, U.S.A.
FAU - Sands, Mark S
AU  - Sands MS
LA  - eng
GR  - R01NS043205/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Biochem Soc Trans
JT  - Biochemical Society transactions
JID - 7506897
RN  - 0 (Membrane Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (PPT1 protein, human)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
SB  - IM
MH  - Animals
MH  - Astrocytes/immunology/metabolism/*pathology
MH  - Gliosis/*etiology
MH  - Humans
MH  - Intermediate Filaments/immunology/metabolism/pathology
MH  - Membrane Proteins/deficiency/genetics/*metabolism
MH  - Mice, Knockout
MH  - Mutation
MH  - Nerve Tissue Proteins/deficiency/genetics/*metabolism
MH  - Neuronal Ceroid-Lipofuscinoses/immunology/metabolism/pathology/*physiopathology
MH  - Thiolester Hydrolases/genetics/*metabolism
EDAT- 2014/09/19 06:00
MHDA- 2015/06/06 06:00
CRDT- 2014/09/19 06:00
PHST- 2014/09/19 06:00 [entrez]
PHST- 2014/09/19 06:00 [pubmed]
PHST- 2015/06/06 06:00 [medline]
AID - BST20140188 [pii]
AID - 10.1042/BST20140188 [doi]
PST - ppublish
SO  - Biochem Soc Trans. 2014 Oct;42(5):1282-5. doi: 10.1042/BST20140188.