Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.2.13 (aldolase)
 3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alzheimer's disease (AD) is the most common human neurodegenerative disease, leading to progressive cognitive decline and eventually death. The prevailing paradigm on the pathogenesis of AD is that abnormally folded proteins accumulate in specific brain areas and lead to neuronal loss via apoptosis. In recent years it has become evident that an inflammatory and possibly autoimmune component exists in AD. Moreover, recent data demonstrate that immunization with amyloid-beta peptide is therapeutically effective in AD. The nature of CNS Ags that are the target of immune attack in AD is unknown. To identify potential autoantigens in AD, we tested sera IgG Abs of AD patients in immunoblots against brain and other tissue lysates. We identified a 42-kDa band in brain lysates that was detected with >50% of 45 AD sera. The band was identified by mass spectrometry to be aldolase A. Western blotting with aldolase using patient sera demonstrated a band of identical size. The Ab reactivity was verified with ELISAs using aldolase. One of 25 elderly control patients and 3 of 30 multiple sclerosis patients showed similar reactivity (p < 0.002). In enzymatic assays, anti-aldolase positive sera were found to inhibit the enzyme's activity, and the presence of the substrate (fructose 1,6-diphosphate) enhanced Ab binding. Immunization of rats and mice with aldolase in complete Freund's adjuvant was not pathogenic. These findings reveal an autoimmune component in AD, point at aldolase as a common autoantigen in this disease, and suggest a new target for potential immune modulation.
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PMID:Identification of aldolase as a target antigen in Alzheimer's disease. 1611 39

Major depressive disorder (MDD) is one of the most common psychiatric disorders. Recent studies have shown a strong association between MDD and peripheral inflammation, shown by a higher incidence of depression in patients with inflammatory diseases including rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis and systemic lupus erythematosus. Dermatomyositis (DM), an idiopathic inflammatory connective tissue disease that is associated with inflammation, predominantly affects the skin and skeletal muscle. The association between DM and MDD in the context of inflammation has seldom been reported. Here we report a 30- year- old Caucasian female with symptoms of depression dating back to 2 years. These symptoms started after cutaneous manifestations of DM. In the past two years, her DM symptoms have worsened that paralleled an increase of depressive symptoms. Also, during the course of the patient's DM, we tracked elevated inflammatory markers including creatine kinase and aldolase, whereas C-reactive protein, C3, and C4 were in a high normal range which correlated with worsening of depression. Hence, a temporal relationship between the onset of MDD and DM symptoms suggests that inflammation may be a common mechanism linking these two conditions.
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PMID:Major Depressive Disorder Following Dermatomyositis: A Case Linking Depression with Inflammation. 2971 2