Glycolytic enzymes from human autoptic brain cortex: Normal aged and demented cases

Iwangoff, P.; Armbruster, Robert; Enz, A.; Meier‐Ruge, W.

doi:10.1016/0047-6374(80)90120-7

Cited by 109 publications

(60 citation statements)

References 3 publications

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“…There is ample evidence that glucose hypometabolism and subsequent bioenergetic depletion may be a significant feature of several neurodegenerative diseases (3,4,68). Indeed, it has been suggested that detachment of hexokinase from the mitochondria may occur in neurodegenerative diseases (69,70). Therefore, experimental strategies directed toward maintaining mitochondrial HKII may be effective both in enhancing glucose metabolism, and in blocking mitochondrial-dependent apoptosis in neuronal cells, which might eventually slow down neurodegeneration in neurological diseases.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Hexokinase II Promotes Neuronal Survival and Acts Downstream of Glycogen Synthase Kinase-3

Giménez-Cassina

Lim

Cerrato

et al. 2009

Journal of Biological Chemistry

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Mitochondrial alterations are detected in most neurodegenerative disorders and may contribute to the dysfunction and demise of neuronal cells. Because glycogen synthase kinase-3 (GSK-3) is considered to be a critical factor in regulating neuronal cell survival and death, we studied the effects of modulating GSK-3 activity in cultured neurons treated with the mitochondrial inhibitor, rotenone. Interestingly, chronic inhibition of GSK-3 protects against rotenone-induced apoptosis in cultured neuronal cells. In an attempt to elucidate the molecular mechanisms underlying this neuroprotection, we demonstrated that chronic inhibition of GSK-3 reprograms the metabolism of neuronal cells, leading to an enhancement of glycolysis. This effect was accompanied by the induction and accumulation of hexokinase II (HKII) in the mitochondria. Interfering with either the mitochondrial binding of HKII or HKII expression significantly diminished the neuroprotection evoked by GSK-3 inhibition, and importantly, HKII overexpression is sufficient to protect against rotenone-induced cell death. Thus, mitochondrial HKII is a promoter of neuronal survival under the regulation of GSK-3. Furthermore, the neuroprotective effect of HKII may be relevant to neurodegenerative diseases in which glucose hypometabolism and mitochondrial dysfunction are prominent features.Most neurodegenerative diseases share certain common features, including mitochondrial dysfunction (reviewed in Refs. 1, 2) and glucose hypometabolism (3, 4), which may contribute to the selective loss of specific neuronal cell populations (5). Rotenone is an inhibitor of the mitochondrial complex I that has been used extensively as a pesticide (6) and that is suspected to be an environmental trigger of Parkinson disease (7,8). Rotenone has also been employed to develop animal models for Parkinson disease, because animals exposed to rotenone display a parkinsonian-like phenotype with nigrostriatal degeneration and the formation of Lewy body inclusions (9 -11). Furthermore, rotenone has also been used to establish cell models of mitochondrial dysfunction and induced neurodegeneration, because there is compelling evidence showing that neurons exposed to rotenone undergo apoptosis (12)(13)(14).Glycogen synthase kinase-3 (GSK-3) 4 is a multifunctional protein kinase that is involved in several cellular processes, such as the regulation of cell metabolism, apoptosis, transcription, and cytoskeleton dynamics (15, 16). It is well known that inhibition of GSK-3 protects neuronal cells from distinct pro-apoptotic stimuli, such as trophic factor withdrawal, ␤-amyloid exposure, excitotoxicity, or prion peptide-induced cell death (17-20). Thus, GSK-3 has been proposed as a possible therapeutic target for neurodegenerative diseases (21).In this study, we show that chronic inhibition of GSK-3 induces significant protection against rotenone-triggered neuronal cell death. We also demonstrate that this neuroprotection is accompanied by an increase in the translocation of hexokinase II (HKII) to mit...

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Section: Discussionmentioning

confidence: 99%

Mitochondrial Hexokinase II Promotes Neuronal Survival and Acts Downstream of Glycogen Synthase Kinase-3

Giménez-Cassina

Lim

Cerrato

et al. 2009

Journal of Biological Chemistry

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“…Additionally, decreased expression of phosphoglycerate mutase 1 has been reported in AD. 66 Loss of function of phosphoglycerate mutase 1 is consistent with altered glucose metabolism in AD 67 and could lead to the accumulation of glycolytic intermediates, decreased production of pyruvate, and, consequently, decreased production and availability of ATP.…”

Section: A␤(1-42) In Vivo Treatment In Ratsmentioning

confidence: 99%

Redox proteomics in some age-related neurodegenerative disorders or models thereof

et al. 2006

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Summary:Neurodegenerative diseases cause memory loss and cognitive impairment. Results from basic and clinical scientific research suggest a complex network of mechanisms involved in the process of neurodegeneration. Progress in treatment of such disorders requires researchers to better understand the functions of proteins involved in neurodegenerative diseases, to characterize their role in pathogenic disease mechanisms, and to explore their roles in the diagnosis, treatment, and prevention of neurodegenerative diseases. A variety of conditions of neurodegenerative diseases often lead to post-translational modifications of proteins, including oxidation and nitration, which might be involved in the pathogenesis of neurodegenerative diseases. Redox proteomics, a subset of proteomics, has made possible the identification of specifically oxidized proteins in neurodegenerative disorders, providing insight into a multitude of pathways that govern behavior and cognition and the response of the nervous system to injury and disease. Proteomic analyses are particularly suitable to elucidate post-translational modifications, expression levels, and protein-protein interactions of thousands of proteins at a time. Complementing the valuable information generated through the integrative knowledge of protein expression and function should enable the development of more efficient diagnostic tools and therapeutic modalities. Here we review redox proteomic studies of some neurodegenerative diseases.

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“…Insulin/IGF resistance, oxidative stress, and metabolic dysfunction in AD Deficits in cerebral glucose utilization and energy metabolism occur very early in the course of AD (Iwangoff, Armbruster et al 1980;Sims, Bowen et al 1980;. Glucose uptake and utilization in brain are dependent upon glucose transport by glucose transporter 4 (GLUT4), which is stimulated by insulin.…”

Section: Insulin/igf Resistance and Amyloid-beta (Aβ) Accumulation Anmentioning

confidence: 99%

Insulin Resistance, Cognitive Impairment and Neurodegeneration: Roles of Nitrosamine Exposure, Diet and Lifestyles

Monte¹,

Tong²,

Wands³

2011

Alzheimer's Disease Pathogenesis-Core Concepts, Shifting Paradigms and Therapeutic Targets

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Glycolytic enzymes from human autoptic brain cortex: Normal aged and demented cases

Cited by 109 publications

References 3 publications

Mitochondrial Hexokinase II Promotes Neuronal Survival and Acts Downstream of Glycogen Synthase Kinase-3

Mitochondrial Hexokinase II Promotes Neuronal Survival and Acts Downstream of Glycogen Synthase Kinase-3

Redox proteomics in some age-related neurodegenerative disorders or models thereof

Insulin Resistance, Cognitive Impairment and Neurodegeneration: Roles of Nitrosamine Exposure, Diet and Lifestyles

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