UZH-Logo

Contribution of hypoxia to Alzheimer's disease: is HIF-1alpha a mediator of neurodegeneration?


Ogunshola, O O; Antoniou, X (2009). Contribution of hypoxia to Alzheimer's disease: is HIF-1alpha a mediator of neurodegeneration? Cellular and Molecular Life Sciences, 66(22):3555-3563.

Abstract

The mammalian brain is extremely sensitive to alterations in cellular homeostasis as a result of environmental or physiological insults. In particular, hypoxic/ischemic challenges (i.e. reduced oxygen and/or glucose delivery) cause severe and detrimental alterations in brain function and can trigger neuronal cell death within minutes. Unfortunately, as we age, oxygen delivery to cells and tissues is impaired, thereby increasing the susceptibility of neurons to damage. Thus, hypoxic (neuronal) adaptation is significantly compromised during aging. Many neurological diseases, such as stroke, Alzheimer's disease (AD), Parkinson's disease and diabetes, are characterized by hypoxia, a state that is believed to only exacerbate disease progression. However, the contribution of hypoxia and hypoxia-mediated pathways to neurodegeneration remains unclear. This review discusses current evidence on the contribution of oxygen deprivation to AD, with an emphasis on hypoxia inducible transcription factor-1 (HIF-1)-mediated pathways and the association of AD with the cytoskeleton regulator cyclin-dependent kinase 5. (Part of a multi-author review.).

The mammalian brain is extremely sensitive to alterations in cellular homeostasis as a result of environmental or physiological insults. In particular, hypoxic/ischemic challenges (i.e. reduced oxygen and/or glucose delivery) cause severe and detrimental alterations in brain function and can trigger neuronal cell death within minutes. Unfortunately, as we age, oxygen delivery to cells and tissues is impaired, thereby increasing the susceptibility of neurons to damage. Thus, hypoxic (neuronal) adaptation is significantly compromised during aging. Many neurological diseases, such as stroke, Alzheimer's disease (AD), Parkinson's disease and diabetes, are characterized by hypoxia, a state that is believed to only exacerbate disease progression. However, the contribution of hypoxia and hypoxia-mediated pathways to neurodegeneration remains unclear. This review discusses current evidence on the contribution of oxygen deprivation to AD, with an emphasis on hypoxia inducible transcription factor-1 (HIF-1)-mediated pathways and the association of AD with the cytoskeleton regulator cyclin-dependent kinase 5. (Part of a multi-author review.).

Citations

52 citations in Web of Science®
59 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

211 downloads since deposited on 19 Oct 2009
8 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Physiology
04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:November 2009
Deposited On:19 Oct 2009 12:40
Last Modified:05 Apr 2016 13:30
Publisher:Springer
ISSN:1420-682X
Additional Information:The original publication is available at www.springerlink.com
Publisher DOI:10.1007/s00018-009-0141-0
PubMed ID:19763399
Permanent URL: http://doi.org/10.5167/uzh-23236

Download

[img]
Preview
Content: Accepted Version
Filetype: PDF
Size: 1MB
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations