. The glial glutamate transporter, GLT-1, is oxidatively modified by 4-hydroxy-2-nonenal in the Alzheimer's disease brain: the role of Abeta1-42. J Neurochem. 2001 Jul;78(2):413-6. PubMed.


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  1. Is Oxidative Damage Specific? Butterfield and colleagues establish that the glutamate transporter (GT) is susceptible to oxidative adduction by the reactive aldehyde hydroxynonenal (HNE) and levels of HNE-modified GT are increased in Alzheimer disease. In vitro treatment of synaptosomes with amyloid-β (Aβ) also resulted in increased GT adduction by HNE, suggesting GT is a target of oxidative attack in Alzheimer disease. It is intriguing that this group has identified a growing list of modified proteins (Bruce-Keller et al., 1998; Pedersen et al., 1998, 2000; Lauderback et al., 2001) with plausible relevance to the disease without addressing the specificity of adduction reactions. Quantitative studies have shown a small number of proteins, e.g., t (Perez et al., 2000; Takeda et al., 2000) and neurofilaments (Wataya, Nunomura, Smith, Perry, unpublished observations), are major targets of HNE-adduction in the CNS, and involve exposure by phosphorylation of lysine in KSP domains. To increase the list by functional, as done by Butterfield and colleagues, rather than specific identification of targets, does not address the biological regulation critically linked to what is now known as "oxidative stress" but may, in time, be appreciated as "oxidative homeostasis". - comment by George Perry and Mark A. Smith


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