Insulin and neurodegenerative disease: shared and specific mechanisms

Craft, Suzanne; Watson, G. Stennis

doi:10.1016/s1474-4422(04)00681-7

Cited by 741 publications

(569 citation statements)

References 138 publications

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“…Numerous clinical studies have shown that there is a biological link between impaired energy metabolism, glucose utilization, and AD pathogenesis (Craft & Watson, 2004; Steen et al ., 2005), which has been confirmed in both cellular and animal models of energy deprivation. Thus, using a pharmacological model of energy metabolism inhibition in Tg2576 mice, Velliquette et al .…”

Section: Discussionmentioning

confidence: 99%

Glucose deprivation increases tau phosphorylation via P38 mitogen‐activated protein kinase

Lauretti

Praticò

2015

Aging Cell

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SummaryAlterations of glucose metabolism have been observed in Alzheimer's disease (AD) brain. Previous studies showed that glucose deprivation increases amyloidogenesis via a BACE‐1‐dependent mechanism. However, no data are available on the effect that this condition may have on tau phosphorylation. In this study, we exposed neuronal cells to a glucose‐free medium and investigated the effect on tau phosphorylation. Compared with controls, cells incubated in the absence of glucose had a significant increase in tau phosphorylation at epitopes Ser202/Thr205 and Ser404, which was associated with a selective activation of the P38 mitogen‐activated protein kinase. Pharmacological inhibition of this kinase prevented the increase in tau phosphorylation, while fluorescence studies revealed its co‐localization with phosphorylated tau. The activation of P38 was secondary to the action of the apoptosis signal‐regulating kinase 1, as its down‐regulation prevented it. Finally, glucose deprivation induced cell apoptosis, which was associated with a significant increase in both caspase 3 and caspase 12 active forms. Taken together, our studies reveal a new mechanism whereby glucose deprivation can modulate AD pathogenesis by influencing tau phosphorylation and suggest that this pathway may be a new therapeutic target for AD.

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Section: Discussionmentioning

confidence: 99%

Glucose deprivation increases tau phosphorylation via P38 mitogen‐activated protein kinase

Lauretti

Praticò

2015

Aging Cell

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“…Previous studies have provided clear evidence that declarative memory formation depends on intact hippocampal functioning (Kessels et al, 2001;Bayley et al, 2005). Hippocampal and cortical insulin signaling pathways have been shown to play a pivotal role in enabling long-term memory consolidation by modulating neuronal activity and triggering mechanisms that are required for establishing synaptic plasticity (Gasparini and Xu, 2003;Zhao et al, 2004;Craft and Watson, 2004;Wada et al, 2005). Thus, it is likely that after intranasal administration, insulin improves neuronal processes within these hippocampal and connected structures.…”

Section: Discussionmentioning

confidence: 99%

Intranasal Insulin Improves Memory in Humans: Superiority of Insulin Aspart

Benedict

Hallschmid

Schmitz

et al. 2006

Neuropsychopharmacol

264

157

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There is compelling evidence that intranasal administration of regular human insulin (RH-I) improves memory in humans. Owing to the reduced tendency of its molecules to form hexamers, the rapid-acting insulin analog insulin aspart (ASP-I) is more rapidly absorbed than RH-I after subcutaneous administration. Since after intranasal insulin administration, ASP-I may also be expected to access the brain, we examined whether intranasal ASP-I has stronger beneficial effects on declarative memory than RH-I in humans. Acute (40 IU) and longterm (4 Â 40 IU/day over 8 weeks) effects of intranasally administered ASP-I, RH-I, and placebo on declarative memory (word lists) were assessed in 36 healthy men in a between-subject design. Plasma insulin and glucose levels were not affected. After 8 weeks of treatment, however, word list recall was improved compared to placebo in both the ASP-I (po0.01) and the RH-I groups (po0.05). ASP-I-treated subjects performed even better than those of the RH-I-treated group (po0.05). Our results indicate that insulin-induced memory improvement can be enhanced by using ASP-I. This finding may be especially relevant for a potential clinical administration of intranasal insulin in the treatment of memory disorders like Alzheimer's disease.

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“…1 They noted that insulin resistance and diabetes may predispose to AD. 2 In this study, APOE e4-negative subjects had a greater drop in fasting insulin in response to rosiglitazone compared to APOE e4-negative subjects. In a smaller preliminary study, Watson et al 3 randomized 30 subjects with mild AD or amnestic mild cognitive impairment to 6 months of rosiglitazone (4 mg daily) or placebo.…”

mentioning

confidence: 55%

Genetic discoveries as the basis of personalized therapy: rosiglitazone treatment of Alzheimer's disease

Hsueh

2006

Pharmacogenomics J

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Insulin and neurodegenerative disease: shared and specific mechanisms

Cited by 741 publications

References 138 publications

Glucose deprivation increases tau phosphorylation via P38 mitogen‐activated protein kinase

Glucose deprivation increases tau phosphorylation via P38 mitogen‐activated protein kinase

Intranasal Insulin Improves Memory in Humans: Superiority of Insulin Aspart

Genetic discoveries as the basis of personalized therapy: rosiglitazone treatment of Alzheimer's disease

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