Free radicals as mediators of toxicity in Alzheimer's disease: a review and hypothesis.
Recent research has increasingly suggested a central role for free radical induced tissue damage in the pathogenesis of Alzheimer's disease (AD). In this paper we review evidence for the interaction between free radicals and other major factors/metabolic areas which have also been implicated in AD, including beta-amyloidosis, inflammatory cytokines, mitochondrial dysfunction and metal ions/homocysteine. We hypothesize that free radicals and antioxidants should not be considered in isolation in the aetiology and treatment of AD. It is the reciprocal induction and self-amplifying interplay between all of the above factors which is important in the pathogenesis of this disorder, and to which multi-pharmacological therapeutic strategies should be directed.
Tabet
N
N
Department of Old Age Psychiatry, Portnalls Unit, Farnborough Hospital, Orpington, Kent BR6 8ND, UK.
Mantle
D
D
Orrell
M
M
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D001923:Brain Chemistry / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D005609:Free Radicals / Q000009:adverse effects* / Q000737:chemistry; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D016207:Cytokines; D005609:Free Radicals; D017382:Reactive Oxygen Species