Metabotropic glutamate receptors prevent nitric oxide‐induced programmed cell death

Vincent, Andrea M.; Mohammad, Y.; Ahmad, Imran Shafiq; Greenberg, Rivka; Maiese, Kenneth

doi:10.1002/(sici)1097-4547(19971115)50:4<549::aid-jnr6>3.3.co;2-e

Cited by 14 publications

(31 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…65 The protective effects of mGluRII activation are not limited to experimental Parkinsonism but include protection against ischemia, 66 excitotoxic damage 67 and nitric oxide-induced programmed cell death. 68 Taken together, it is possible to suggest that the modulation of glutamatergic systems might be of clinical relevance by virtue, at least in part, of increased BDNF production implying that the neurotrophin might actively participate in affording neuroprotection in PD.…”

Section: Glutamatergic Drugsmentioning

confidence: 99%

Shedding light into the role of BDNF in the pharmacotherapy of Parkinson's disease

Fumagalli¹,

Racagni

Riva³

2006

Pharmacogenomics J

120

View full text Add to dashboard Cite

Parkinson's disease (PD) is a chronic, neurodegenerative disease with a 1% incidence in the population over 55 years of age. Movement impairments represent undoubtedly the hallmark of the disorder; however, extensive evidence implicates cognitive deficits as concomitant peculiar features. Brainderived neurotrophic factor (BDNF) colocalizes with dopamine neurons in the substantia nigra, where dopaminergic cell bodies are located, and it has recently garnered attention as a molecule crucial for cognition, a function that is also compromised in PD patients. Thus, due to its colocalization with dopaminergic neurons and its role in cognition, BDNF might possess a dual role in PD, both as a neuroprotective molecule, since its inhibition leads to loss of nigral dopaminergic neurons, and as a neuromodulator, as its enhanced expression ameliorates cognitive processes. In this review, we discuss the mechanism of action of established as well as novel drugs for PD with a particular emphasis to those interfering with BDNF biosynthesis.

show abstract

Section: Glutamatergic Drugsmentioning

confidence: 99%

Shedding light into the role of BDNF in the pharmacotherapy of Parkinson's disease

Fumagalli¹,

Racagni

Riva³

2006

Pharmacogenomics J

120

View full text Add to dashboard Cite

show abstract

“…Current interest has focused on the protective role of the mGluR system in the nervous system. mGluR activation prevents and, in some cases, reverses genomic DNA degradation [236], modulates endonuclease activation [237], and maintains cellular membrane asymmetry [235]. Cytoprotection by the mGluR system is believed to act at or below the level of free radical generation and oxidative stress [143,192,236].…”

Section: Modulation Of the Metabotropic Glutamate Systemmentioning

confidence: 99%

“…mGluR activation prevents and, in some cases, reverses genomic DNA degradation [236], modulates endonuclease activation [237], and maintains cellular membrane asymmetry [235]. Cytoprotection by the mGluR system is believed to act at or below the level of free radical generation and oxidative stress [143,192,236]. More recent work has suggested that mGluR offers similar protective capacity to the vascular system by preventing endothelial cell DNA degradation, caspase activity, and inhibiting a thrombotic state through the maintenance of membrane asymmetry [125,124,142].…”

Section: Modulation Of the Metabotropic Glutamate Systemmentioning

confidence: 99%

Stress in the brain: novel cellular mechanisms of injury linked to Alzheimer's disease

Chong

Maiese

2005

Brain Research Reviews

135

121

View full text Add to dashboard Cite

More than a century has elapsed since the description of Alois Alzheimer's patient Auguste D. Yet, the well-documented generation of β-amyloid aggregates and neurofibrillary tangles that define Alzheimer's disease is believed to represent only a portion of the cellular processes that can determine the course of Alzheimer's disease. Understanding of the complex nature of this disorder has evolved with an increased appreciation for pathways that involve the generation of reactive oxygen species and oxidative stress, apoptotic injury that leads to nuclear degradation in both neuronal and vascular populations, and the early loss of cellular membrane asymmetry that mitigates inflammation and vascular occlusion. Recent work has identified novel pathways, such as the Wnt pathway and the serine-threonine kinase Akt, as central modulators that oversee cellular apoptosis and the formation of neurofibrillary tangles through their downstream substrates that include glycogen synthase kinase-3β, Bad, and Bcl-x L . Other closely integrated pathways control microglial activation, release of inflammatory cytokines, and caspase and calpain activation for the processing of amyloid precursor protein, tau protein cleavage, and presenilin disposal. New therapeutic avenues that are just open to exploration, such as with nicotinamide adenine dinucleotide modulation, cell cycle modulation, metabotropic glutamate system modulation, and erythropoietin targeted expression, may provide both attractive and viable alternatives to treat Alzheimer's disease.

show abstract

“…Current interest has focused on the protective role of the mGluR system in the nervous system. mGluR activation prevents, and in some cases, reverses genomic DNA degradation (Vincent, AM et al, 1997), modulates endonuclease activation , and maintains cellular membrane asymmetry . Cytoprotection by the mGluR system is believed to act at or below the level of free radical generation and oxidative stress (Maiese, K et al, 1996, Sagara, Y and Schubert, D, 1998, Vincent, AM et al, 1997.…”

Section: The Metabotropic Glutamate System During Neurodegenerationmentioning

confidence: 99%

“…mGluR activation prevents, and in some cases, reverses genomic DNA degradation (Vincent, AM et al, 1997), modulates endonuclease activation , and maintains cellular membrane asymmetry . Cytoprotection by the mGluR system is believed to act at or below the level of free radical generation and oxidative stress (Maiese, K et al, 1996, Sagara, Y and Schubert, D, 1998, Vincent, AM et al, 1997. More recent work has suggested that the mGluR offers similar protective capacity to the vascular system by preventing endothelial cell DNA degradation, caspase activity, and inhibiting a thrombotic state through the maintenance of membrane asymmetry (Lin, S-H et al, 2002, Lin, SH et al, 2001.…”

Section: The Metabotropic Glutamate System During Neurodegenerationmentioning

confidence: 99%

Employing New Cellular Therapeutic Targets for Alzheimers Disease: A Change for the Better?

Chong¹,

Li²,

Maiese³

2005

CNR

View full text Add to dashboard Cite

Alzheimer's disease is a progressive disorder that results in the loss of cognitive function and memory. Although traditionally defined by the presence of extracellular plaques of amyloid-β peptide aggregates and intracellular neurofibrillary tangles in the brain, more recent work has begun to focus on elucidating the complexities of Alzheimer's disease that involve the generation of reactive oxygen species and oxidative stress. Apoptotic processes that are incurred as a function of oxidative stress affect neuronal, vascular, and monocyte derived cell populations. In particular, it is the early apoptotic induction of cellular membrane asymmetry loss that drives inflammatory microglial activation and subsequent neuronal and vascular injury. In this article, we discuss the role of novel cellular pathways that are invoked during oxidative stress and may potentially mediate apoptotic injury in Alzheimer's disease. Ultimately, targeting new avenues for the development of therapeutic strategies linked to mechanisms that involve inflammatory microglial activation, cellular metabolism, cell-cycle regulation, G-protein regulated receptors, and cytokine modulation may provide fruitful gains for both the prevention and treatment of Alzheimer's disease. Keywordsβ-Amyloid; Akt; caspases; erythropoietin; Forkhead transcription factors; metabotropic; microglia; nicotinamide; Wnt PATHOPHYSIOLOGY AND MEDICAL IMPLICATIONS OF ALZHEIMER'S DISEASENeuronal injury during Alzheimer's disease predominantly occurs in the hippocampus and the cortex. The disorder leads to a progressive deterioration of cognitive function with loss of memory and is characterized by two pathologic hallmarks that consist of extracellular plaques of amyloid-β peptide aggregates and intracellular neurofibrillary tangles composed of hyperphosphorylated microtubular protein tau. The β-amyloid deposition that constitutes the plaques is composed of a 39−42 amino acid peptide (Aβ), which is the proteolytic product of the amyloid precursor protein (APP) .With an aging population, medical costs for neurodegenerative disease parallel a progressive loss of economic productivity with increasing morbidity and mortality. The cost of physician

show abstract

Metabotropic glutamate receptors prevent nitric oxide‐induced programmed cell death

Cited by 14 publications

References 0 publications

Shedding light into the role of BDNF in the pharmacotherapy of Parkinson's disease

Shedding light into the role of BDNF in the pharmacotherapy of Parkinson's disease

Stress in the brain: novel cellular mechanisms of injury linked to Alzheimer's disease

Employing New Cellular Therapeutic Targets for Alzheimers Disease: A Change for the Better?

Contact Info

Product

Resources

About