Format

Send to

Choose Destination
Int J Mol Sci. 2015 Mar 9;16(3):5400-19. doi: 10.3390/ijms16035400.

A heme oxygenase-1 transducer model of degenerative and developmental brain disorders.

Author information

1
Bloomfield Centre for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC H3T1E2, Canada. hyman.schipper@mcgill.ca.
2
Department of Neurology & Neurosurgery and Department of Medicine, McGill University and Jewish General Hospital, Montreal, QC H3T1E2, Canada. hyman.schipper@mcgill.ca.
3
Bloomfield Centre for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC H3T1E2, Canada. wsong39@yahoo.com.

Abstract

Heme oxygenase-1 (HO-1) is a 32 kDa protein which catalyzes the breakdown of heme to free iron, carbon monoxide and biliverdin. The Hmox1 promoter contains numerous consensus sequences that render the gene exquisitely sensitive to induction by diverse pro-oxidant and inflammatory stimuli. In "stressed" astroglia, HO-1 hyperactivity promotes mitochondrial iron sequestration and macroautophagy and may thereby contribute to the pathological iron deposition and bioenergetic failure documented in Alzheimer disease, Parkinson disease and certain neurodevelopmental conditions. Glial HO-1 expression may also impact neuroplasticity and cell survival by modulating brain sterol metabolism and the proteasomal degradation of neurotoxic proteins. The glial HO-1 response may represent a pivotal transducer of noxious environmental and endogenous stressors into patterns of neural damage and repair characteristic of many human degenerative and developmental CNS disorders.

PMID:
25761244
PMCID:
PMC4394483
DOI:
10.3390/ijms16035400
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center