Neuroprotective strategies for treatment of lesions produced by mitochondrial toxins: Implications for neurodegenerative diseases

Schulz, Jörg B.; Matthews, Russell T.; Henshaw, D. Ross; Beal, M. Flint

doi:10.1016/0306-4522(95)00527-7

Cited by 141 publications

(66 citation statements)

References 24 publications

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“…Memantine is a versatile agent exhibiting neuroprotective effects in several models of neurodegeneration, including ischemia (Ehrlich et al, 1999), oxygenglucose deprivation (Frankiewicz et al, 2000) and amyloid β-induced neurotoxicity (MiguelHidalgo et al, 2002, Yamada et al, 2005. Schulz et al (1996), reported that memantine prevented the volumetric changes in the mouse striatum following administration of malonate, a complex II inhibitor, demonstrating that memantine could be used to prevent the deleterious effects of mitochondrial dysfunction. In vitro studies have shown that memantine diminishes the toxicity induced by 3-nitropropionic acid, another complex II inhibitor, in cerebellar granular cell cultures (Volbracht et al, 2006), cholinergic neurons (Wenk et al, 1996), and hippocampal slices (Karanian et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of memantine in a mouse model of retinal degeneration induced by rotenone

2008

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This is the first report of the in vivo effectiveness of memantine as a neuroprotective agent against rotenone-induced retinal toxicity. We tested the hypothesis that uncompetitive NMDAR blockade with memantine prevents mitochondrial dysfunction-related neurodegeneration in vivo, using a mouse model of retinal ganglion cell layer (GCL) degeneration induced by rotenone, a mitochondrial complex I inhibitor. Rotenone induced an increase in cell death and oxidative stress in GCL compared to controls, and these changes were prevented by the co-administration of memantine. The neurotoxic effect of rotenone was also reflected as a decrease in total cell density in GCL and GCL + nerve fiber layer thickness. These changes were also prevented by co-administration of memantine in a dosedependent manner. In addition, memantine induced an increase in long-term retinal energy metabolic capacity. The results suggest that NMDAR activation contributes to cell death induced by mitochondrial dysfunction and that uncompetitive NMDAR blockade may be used as a neuroprotective strategy against mitochondrial dysfunction in neurodegenerative diseases. SectionDisease-related neuroscience

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Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of memantine in a mouse model of retinal degeneration induced by rotenone

2008

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“…In this model of neuronal injury [204] GT 715 was observed to significantly decrease the brain injury induced by the malonate neurotoxin at both the behavioural and neurochemical levels. Preservation of GABA levels in the striatum after malonate injection, measured as an index of the neuronal cell population, and a markedly decreased response to apomorphine in ipsolateral turning indicated that neuronal injury was significantly inhibited by GT 715 administration, and that normal function within the neostriatum was maintained [202].…”

Section: Nitrates As No Mimetic Therapeutics In Admentioning

confidence: 82%

Nitric Oxide Mimetic Molecules as Therapeutic Agents in Alzheimers Disease

Thatcher

Bennett²,

Reynolds³

2005

CAR

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Nitric oxide is multifunctional messenger molecule in the brain, playing important roles including in learning and memory and in regulating the expression of trophic factors that may be reduced with aging. Small molecules that mimic the biological activity of NO, NO mimetics, will bypass cholinergic receptor activation and are anticipated to provide multiple pathways of treating and circumventing dementia in Alzheimer's disease. Activation of soluble guanylyl cyclase and cGMP formation in the brain represents one element of effective neuroprotective pathways mediated by NO. Substantial evidence suggests that NO mimetics may display cGMP-dependent and cGMP-independent activity and may operate via multiple biochemical signaling pathways, both to ensure the survival of neurons subjected to stress and also to provide cognition-enabling pathways to circumvent dementia. GT 1061 is an NO mimetic compound currently in clinical trials for Alzheimer's. A survey of current research indicates that NO mimetics will provide a combined neuroprotective and cognition-enabling approach to anti-neurodegenerative therapy.

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“…The influence of aluminum on the cerebrum ala nine aminotransferase (ALAT) activities with different doses of ethanol exposure showed that neither alu minum nor ethanol had statistically significant 28 influence. However, the interaction between the expo sures was found to have significant (F 4,50 = 3.13, P < 0.05) influence on the alterations of ALAT activities of the cerebrum.…”

Section: Resultsmentioning

confidence: 99%

“…The enzyme in mitochondria is latent and can be 'activated' by various procedures that disrupt the mitochondrial structure. The critical role of mitochondrial dysfunction in the pathogenesis of age-related nerve cell degeneration has been suggested on several occasions (27,28). On the other hand, coexposure of aluminum and glutamate is reported to produce morphological abnormalities of mitochondrial structures in pyramidal neurons of hippocampal formation, which are not observed when exposed to aluminum or glutamate alone (29).…”

Section: Discussionmentioning

confidence: 99%

Impact of Coexposure to Aluminum and Ethanol on Phosphoesterases and Transaminases of Rat Cerebrum

Nayak¹,

Sharma²,

Chowdary³

2011

Journal of Medical Biochemistry

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Kratak sadr`aj: Sveprisutnost aluminijuma uz njegovu ne kontrolisanu upotrebu kao i trend sve ve}e konzumacije etanola u Indiji pove}ali su mogu}nost dvostruke izlo`e nosti aluminijumu i etanolu. Mogu}e je da oba prate zajednike mehanizme u proizvodnji neurotoksi~nosti. Fosfo mono esteraze i glutamat-transaminaze ispitivane su u velikom mozgu pacova posle kombinovane izlo`enosti aluminijumu i razli~itim dozama etanola tokom 4 nedelje. Uo~ena su smanjenja rasta zavisna od doze. Pokazano je da se uticaj aluminijuma na aktivnosti mo`dane kisele i alkalne fosfomonoesteraze menja u zavisnosti od doze usled dvostruke izlo`enosti etanolu. Aspartat-aminotransferaza i alanin-amino transferaza u velikom mozgu davale su razli~it odgovor na izlo`enost aluminijumu u prisustvu razli~itih doza izloenosti etanolu. Pokazano je da poja~anje uticaja aluminijuma na mozak izazvano etanolom zavisi od doze i da za opa`eni efekat na mozak mo`e postojati kriti~an nivo izloenosti etanolu.

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Neuroprotective strategies for treatment of lesions produced by mitochondrial toxins: Implications for neurodegenerative diseases

Cited by 141 publications

References 24 publications

Neuroprotective effects of memantine in a mouse model of retinal degeneration induced by rotenone

Neuroprotective effects of memantine in a mouse model of retinal degeneration induced by rotenone

Nitric Oxide Mimetic Molecules as Therapeutic Agents in Alzheimers Disease

Impact of Coexposure to Aluminum and Ethanol on Phosphoesterases and Transaminases of Rat Cerebrum

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