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Nutritional antioxidants and the heme oxygenase pathway of stress tolerance: novel targets for neuroprotection in Alzheimer's disease.

Abstract

Oxidative stress has been implicated in mechanisms leading to neuronal cell injury in various pathological states of the brain. Alzheimer's disease (AD) is a progressive disorder with cognitive and memory decline, speech loss, personality changes and synapse loss. Many approaches have been undertaken to understand AD, but the heterogeneity of the etiologic factors makes it difficult to define the clinically most important factor determining the onset and progression of the disease. However, increasing evidence indicates that factors such as oxidative stress and disturbed protein metabolism and their interaction in a vicious cycle are central to AD pathogenesis. Brains of AD patients undergo many changes, such as disruption of protein synthesis and degradation, classically associated with the heat shock response, which is one form of stress response. Heat-shock proteins are proteins serving as molecular chaperones involved in the protection of cells from various forms of stress. Recently, the involvement of the heme oxygenase (HO) pathway in anti-degenerative mechanisms operating in AD has received considerable attention, as it has been demonstrated that the expression of HO is closely related to that of amyloid precursor protein (APP). HO induction, which occurs together with the induction of other HSPs during various physiopathological conditions, by generating the vasoactive molecule carbon monoxide and the potent antioxidant bilirubin, represents a protective system potentially active against brain oxidative injury. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing the heat shock response. Recently, increasing interest has been focused on identifying dietary compounds that can inhibit, retard or reverse the multi-stage pathophysiological events underlying AD pathology. Alzheimer's disease, in fact, involves a chronic inflammatory response associated with both brain injury and beta-amyloid associated pathology. Spice and herbs contain phenolic substances with potent antioxidative and chemopreventive properties, and it is generally assumed that the phenol moiety is responsible for the antioxidant activity. In particular, curcumin, a powerful antioxidant derived from the curry spice turmeric, has emerged as a strong inducer of the heat shock response. In light of this finding, curcumin supplementation has been recently considered as an alternative, nutritional approach to reduce oxidative damage and amyloid pathology associated with AD. Here we review the importance of the heme oxygenase pathway in brain stress tolerance and its significance as antidegenerative mechanism operating in AD pathogenesis. We also discuss the role that exogenous antioxidant supplementation, conceivably, could play in AD in combating oxidative damage and compensating for the decreased level of endogenous antioxidants. Conceivably, dietary supplementation with vitamin E or with polyphenolic agents, such as curcumin and its derivatives, can forestall the development of AD, consistent with a major "metabolic" component to this disorder. Such an outcome would provide optimism that the signs and symptoms of this devastating brain disorder of aging may be largely delayed and/or modulated.

Authors+Show Affiliations

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Section of Biochemistry and Molecular Biology, Department of Chemistry, Faculty of Medicine, University of Catania, Catania, Italy. calabres@mbox.unict.it

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Source

The Italian journal of biochemistry 52:4 2003 Dec pg 177-81

MeSH

Alzheimer Disease
Antioxidants
Dietary Supplements
Heme Oxygenase (Decyclizing)
Humans
Neuroprotective Agents
Oxidative Stress

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

15141484

Citation

Calabrese, Vittorio, et al. "Nutritional Antioxidants and the Heme Oxygenase Pathway of Stress Tolerance: Novel Targets for Neuroprotection in Alzheimer's Disease." The Italian Journal of Biochemistry, vol. 52, no. 4, 2003, pp. 177-81.
Calabrese V, Butterfield DA, Stella AM. Nutritional antioxidants and the heme oxygenase pathway of stress tolerance: novel targets for neuroprotection in Alzheimer's disease. Ital J Biochem. 2003;52(4):177-81.
Calabrese, V., Butterfield, D. A., & Stella, A. M. (2003). Nutritional antioxidants and the heme oxygenase pathway of stress tolerance: novel targets for neuroprotection in Alzheimer's disease. The Italian Journal of Biochemistry, 52(4), pp. 177-81.
Calabrese V, Butterfield DA, Stella AM. Nutritional Antioxidants and the Heme Oxygenase Pathway of Stress Tolerance: Novel Targets for Neuroprotection in Alzheimer's Disease. Ital J Biochem. 2003;52(4):177-81. PubMed PMID: 15141484.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nutritional antioxidants and the heme oxygenase pathway of stress tolerance: novel targets for neuroprotection in Alzheimer's disease. AU - Calabrese,Vittorio, AU - Butterfield,D Allan, AU - Stella,Anna M Giuffrida, PY - 2004/5/15/pubmed PY - 2004/12/29/medline PY - 2004/5/15/entrez SP - 177 EP - 81 JF - The Italian journal of biochemistry JO - Ital. J. Biochem. VL - 52 IS - 4 N2 - Oxidative stress has been implicated in mechanisms leading to neuronal cell injury in various pathological states of the brain. Alzheimer's disease (AD) is a progressive disorder with cognitive and memory decline, speech loss, personality changes and synapse loss. Many approaches have been undertaken to understand AD, but the heterogeneity of the etiologic factors makes it difficult to define the clinically most important factor determining the onset and progression of the disease. However, increasing evidence indicates that factors such as oxidative stress and disturbed protein metabolism and their interaction in a vicious cycle are central to AD pathogenesis. Brains of AD patients undergo many changes, such as disruption of protein synthesis and degradation, classically associated with the heat shock response, which is one form of stress response. Heat-shock proteins are proteins serving as molecular chaperones involved in the protection of cells from various forms of stress. Recently, the involvement of the heme oxygenase (HO) pathway in anti-degenerative mechanisms operating in AD has received considerable attention, as it has been demonstrated that the expression of HO is closely related to that of amyloid precursor protein (APP). HO induction, which occurs together with the induction of other HSPs during various physiopathological conditions, by generating the vasoactive molecule carbon monoxide and the potent antioxidant bilirubin, represents a protective system potentially active against brain oxidative injury. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing the heat shock response. Recently, increasing interest has been focused on identifying dietary compounds that can inhibit, retard or reverse the multi-stage pathophysiological events underlying AD pathology. Alzheimer's disease, in fact, involves a chronic inflammatory response associated with both brain injury and beta-amyloid associated pathology. Spice and herbs contain phenolic substances with potent antioxidative and chemopreventive properties, and it is generally assumed that the phenol moiety is responsible for the antioxidant activity. In particular, curcumin, a powerful antioxidant derived from the curry spice turmeric, has emerged as a strong inducer of the heat shock response. In light of this finding, curcumin supplementation has been recently considered as an alternative, nutritional approach to reduce oxidative damage and amyloid pathology associated with AD. Here we review the importance of the heme oxygenase pathway in brain stress tolerance and its significance as antidegenerative mechanism operating in AD pathogenesis. We also discuss the role that exogenous antioxidant supplementation, conceivably, could play in AD in combating oxidative damage and compensating for the decreased level of endogenous antioxidants. Conceivably, dietary supplementation with vitamin E or with polyphenolic agents, such as curcumin and its derivatives, can forestall the development of AD, consistent with a major "metabolic" component to this disorder. Such an outcome would provide optimism that the signs and symptoms of this devastating brain disorder of aging may be largely delayed and/or modulated. SN - 0021-2938 UR - https://www.unboundmedicine.com/medline/citation/15141484/Nutritional_antioxidants_and_the_heme_oxygenase_pathway_of_stress_tolerance:_novel_targets_for_neuroprotection_in_Alzheimer's_disease_ L2 - https://medlineplus.gov/alzheimersdisease.html DB - PRIME DP - Unbound Medicine ER -