Send to

Choose Destination
Exp Gerontol. 2000 Sep;35(6-7):821-30.

Heme oxygenase-1: role in brain aging and neurodegeneration.

Author information

Bloomfield Centre for Research in Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Que., H3T 1E2, Montreal, Canada.


The mechanisms responsible for excessive iron deposition and mitochondrial insufficiency in the aging and degenerating nervous system remain poorly understood. Heme oxygenase-1 (HO-1) is a 32kDa stress protein that degrades heme to biliverdin, free iron and carbon monoxide. Our laboratory has shown that cysteamine, dopamine, beta-amyloid, IL-1beta and TNF-alpha up-regulate HO-1 followed by mitochondrial sequestration of non-transferrin-derived 55Fe in cultured rat astroglia. In these cells and in rat astroglia transfected with the human HO-1 gene, mitochondrial iron trapping is abrogated by the HO-1 inhibitors, tin-mesoporphyrin and dexamethasone. We determined that HO-1 immunoreactivity is enhanced greatly in neurons and astrocytes of the hippocampus and cerebral cortex of Alzheimer subjects and co-localizes to senile plaques and neurofibrillary tangles (NFT). HO-1 staining is also augmented in astrocytes and decorates neuronal Lewy bodies in the Parkinson nigra. Collectively, our findings suggest that HO-1 over-expression contributes to the pathological iron deposition and mitochondrial damage documented in these aging-related neurodegenerative disorders. We recently observed that, paradoxically, HO-1 mRNA levels are markedly suppressed in peripheral lymphocytes of patients with early sporadic Alzheimer disease and may thus provide a useful biological marker of this condition.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center