The heme oxygenases (HOs), responsible for the degradation of heme to biliverdin/bilirubin, free iron and CO, have been heavily implicated in mammalian CNS aging and disease. In normal brain, the expression of HO-2 is constitutive, abundant and fairly ubiquitous, whereas HO-1 mRNA and protein are confined to small populations of scattered neurons and neuroglia. In contradistinction to HO-2, the ho-1 gene (Hmox1) is exquisitely sensitive to induction by a wide range of pro-oxidant and other stressors. In Alzheimer disease and mild cognitive impairment, immunoreactive HO-1 protein is over-expressed in neurons and astrocytes of the cerebral cortex and hippocampus relative to age-matched, cognitively intact controls and co-localizes to senile plaques, neurofibrillary tangles, and corpora amylacea. In Parkinson disease, HO-1 is markedly over-expressed in astrocytes of the substantia nigra and decorates Lewy bodies in affected dopaminergic neurons. HMOX1 is also up-regulated in glial cells surrounding human cerebral infarcts, hemorrhages and contusions, within multiple sclerosis plaques, and in other degenerative and inflammatory human CNS disorders. Heme-derived free ferrous iron, CO, and biliverdin/bilirubin are biologically active substances that have been shown to either ameliorate or exacerbate neural injury contingent upon specific disease models employed, the intensity and duration of HO-1 expression and the nature of the prevailing redox microenvironment. In 'stressed' astroglia, HO-1 hyperactivity promotes mitochondrial sequestration of non-transferrin iron and macroautophagy and may thereby contribute to the pathological iron deposition and bioenergetic failure amply documented in Alzheimer disease, Parkinson disease and other aging-related neurodegenerative disorders. Glial HO-1 expression may also impact cell survival and neuroplasticity in these conditions by modulating brain sterol metabolism and proteosomal degradation of neurotoxic protein aggregates.

EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001E43 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001E43 | SxmlIndent | more

{{Explor lien
   |wiki=    Wicri/Canada
   |area=    ParkinsonCanadaV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     pubmed:19457088
   |texte=   Heme oxygenase-1 and neurodegeneration: expanding frontiers of engagement.
}}

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:19457088" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a ParkinsonCanadaV1