Studies on Intermediate Carbohydrate Metabolism in Multiple Sclerosis

McArdle, B.; Mackenzie, Ian C.; Webster, G. R.

doi:10.1136/jnnp.23.2.127

Cited by 22 publications

(13 citation statements)

References 9 publications

(18 reference statements)

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“…Glucose is central to energy metabolism in the brain, both in astrocytes and neurons, and defects in glucose metabolic pathways have been documented in neurodegenerative disorders (Mathur, Lopez‐Rodas, Casanova, & Marti, ): Pyruvate levels are increased in patients with multiple sclerosis (McArdle, Mackenzie, & Webster, ), while impaired GAPDH and ECT components were found in both AD and HD patients (Brooks et al, ; Chandrasekaran et al, ; Mazzola & Sirover, ; Regenold, Phatak, Makley, Stone, & Kling, ). How metabolic deregulation is involved in functional changes in the aging brain, however, is largely unknown.…”

Section: Discussionmentioning

confidence: 99%

JNK modifies neuronal metabolism to promote proteostasis and longevity

et al. 2019

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Aging is associated with a progressive loss of tissue and metabolic homeostasis. This loss can be delayed by single‐gene perturbations, increasing lifespan. How such perturbations affect metabolic and proteostatic networks to extend lifespan remains unclear. Here, we address this question by comprehensively characterizing age‐related changes in protein turnover rates in the Drosophila brain, as well as changes in the neuronal metabolome, transcriptome, and carbon flux in long‐lived animals with elevated Jun‐N‐terminal Kinase signaling. We find that these animals exhibit a delayed age‐related decline in protein turnover rates, as well as decreased steady‐state neuronal glucose‐6‐phosphate levels and elevated carbon flux into the pentose phosphate pathway due to the induction of glucose‐6‐phosphate dehydrogenase (G6PD). Over‐expressing G6PD in neurons is sufficient to phenocopy these metabolic and proteostatic changes, as well as extend lifespan. Our study identifies a link between metabolic changes and improved proteostasis in neurons that contributes to the lifespan extension in long‐lived mutants.

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Section: Discussionmentioning

confidence: 99%

JNK modifies neuronal metabolism to promote proteostasis and longevity

et al. 2019

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“…This is similar to the pattern of biochemical changes reported in classical motor neurone disease (MND) under similar experimental conditions (Cumings, 1962;Shahani et al, 1971). The elevated plasma pyruvate level in classical MND has been attributed to many factors such as pancreatic dysfunction (Quick, 1969), spasticity (McArdle, Mackenzie, and Webster, 1960), and others. In our series of MND-Madras, the plasma amylase level is well within normal limits ( Table 2), indicative of normal pancreatic function.…”

Section: Discussionmentioning

confidence: 99%

Biochemical aspects of motor neurone disease--Madras pattern

Valmikinathan

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Meenakshisundaram

et al. 1973

Journal of Neurology, Neurosurgery & Psychiatry

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“…Several factors may have been responsible, to a greater or lesser degree, for the abnormal pyruvate concentration in these patients. Dysphagia secondary to bulbar involvement, malabsorption and vitamin Bi deficiency due to pancreatic dysfunction (Quick, 1969), and spasticity (McArdle, MacKenzie, and Webster, 1960) can all give rise to abnormal serum pyruvate levels. These factors, however, were probably not relevant because there was neither evidence of malnutrition, nor any relationship between the abnormal pyruvate metabolism and the degree of spasticity.…”

Section: Fig 2 Patient With Mnd (Ns) Experimental Conditions As Inmentioning

confidence: 99%