Hyperammonemia and Alzheimer's Disease

Fisman, Michael; Ball, Melvin; Blume, Warren T.

doi:10.1111/j.1532-5415.1989.tb06935.x

Cited by 16 publications

(8 citation statements)

References 2 publications

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“…This aspect is particularly important in view of the grow ing evidence for the role of the endosomal lysosomal sys tem in the formation of amyloidogenic fragments from the beta-amyloid precursor protein. Although ammonia cannot be considered as a primary factor of DAT, hyperammonemia and ammonia release from the brains of such patients is now well supported by published observations [57][58][59]. Although the age-related impairment of liver function could be contributing (and why not a specific impairment of hepatic function in Alz heimer's disease), excessive ammonia formation by pro teolytic processes and oxidative deamination, together with the impairment of the physiological detoxication mechanisms, are more likely to be the main causes of dementia hyperammonemia.…”

Section: Ammonia (Nh3; I\1h4+)supporting

confidence: 51%

Potential Biological Targets for Anti-Alzheimer Drugs

Allain

Belliard²,

Certaines³

et al. 1993

Dement Geriatr Cogn Disord

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The stunning accumulation of data on the physiopathology of Alzheimer''s disease is a real hindrance to pharmacologists who have to make decisions as to what molecules should be assessed first in man. Considering the cumbersomeness and cost of clinical trials in that field, a review of potential targets for drugs that are supposed to be active against the disease has become necessary, for a true definition of the rational justifications of trials to be envisaged.

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Section: Ammonia (Nh3; I\1h4+)supporting

confidence: 51%

Potential Biological Targets for Anti-Alzheimer Drugs

Allain

Belliard²,

Certaines³

et al. 1993

Dement Geriatr Cogn Disord

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“…Moreover, in this context it has been reported that ammonia levels are increased in blood and brain of patients with AD. [34][35][36] We may postulate that the urea cycle is activated following increased OTC gene expression under certain pathological conditions in order to compensate for both decreased GS activity and increased ammonia concentration. Another main function of the urea cycle is to participate in the production of NO via synthesis of arginine, the substrate for nitric oxide synthase.…”

Section: Discussionmentioning

confidence: 99%

Evidence for induction of the ornithine transcarbamylase expression in Alzheimer's disease

et al. 2007

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To more rapidly identify candidate genes located within chromosomal regions of interest defined by genome scan studies in Alzheimer's disease (AD), we have developed a customized microarray containing all the ORFs (n = 2741) located within nine of these regions. Levels of gene expression were assessed in total RNA from brain tissue of 12 controls and 12 AD patients. Of all genes showing differential expression, we focused on the ornithine transcarbamylase (OTC) gene on Xp21.1., a key enzyme of the urea cycle which we found to be expressed in AD brains but not in controls, as confirmed by RT-PCR. We also detected mRNA expression of all the other urea cycle enzymes in AD brains. Immunochemistry experiments revealed that the OTC expression was strictly restricted to vascular endothelial cells in brain. Furthermore, OTC activity was 880% increased in the CSF of probable AD cases compared with controls. We analysed the association of the OTC À389 G/A and À241 A/G promoter polymorphisms with the risk of developing AD. We observed that rare haplotypes may be associated with the risk of AD through a possible modulation of the methylation of the OTC promoter. In conclusion, our results suggest the involvement of a new pathway in AD brains involving the urea cycle.

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“…Ammonia is one of the end-products of protein catabolism, historically implicated in the pathogenesis of AD [63]. Due to its neurotoxic nature even at low concentrations, an efficient astrocyte-modulated brain ammonia detoxification through the formation of glutamine by glutamine synthetase (GS) is crucial [64].…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Gut Microbiota in Alzheimer’s Disease, Depression, and Type 2 Diabetes Mellitus: The Role of Oxidative Stress

Luca

Mauro

Luca

2019

Oxidative Medicine and Cellular Longevity

125

111

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Gut microbiota consists of over 100 trillion microorganisms including at least 1000 different species of bacteria and is crucially involved in physiological and pathophysiological processes occurring in the host. An imbalanced gastrointestinal ecosystem (dysbiosis) seems to be a contributor to the development and maintenance of several diseases, such as Alzheimer’s disease, depression, and type 2 diabetes mellitus. Interestingly, the three disorders are frequently associated as demonstrated by the high comorbidity rates. In this review, we introduce gut microbiota and its role in both normal and pathological processes; then, we discuss the importance of the gut-brain axis as well as the role of oxidative stress and inflammation as mediators of the pathological processes in which dysbiosis is involved. Specific sections pertain the role of the altered gut microbiota in the pathogenesis of Alzheimer’s disease, depression, and type 2 diabetes mellitus. The therapeutic implications of microbiota manipulation are briefly discussed. Finally, a conclusion comments on the possible role of dysbiosis as a common pathogenetic contributor (via oxidative stress and inflammation) shared by the three disorders.

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Hyperammonemia and Alzheimer's Disease

Cited by 16 publications

References 2 publications

Potential Biological Targets for Anti-Alzheimer Drugs

Potential Biological Targets for Anti-Alzheimer Drugs

Evidence for induction of the ornithine transcarbamylase expression in Alzheimer's disease

Gut Microbiota in Alzheimer’s Disease, Depression, and Type 2 Diabetes Mellitus: The Role of Oxidative Stress

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