The loss of pigmented neurons from the human brain has long been the hallmark of Parkinson＇s disease（PD）.Neuromelanin（NM） in the pre-synaptic terminal of dopamine neurons is emerging as a primary player in the et...The loss of pigmented neurons from the human brain has long been the hallmark of Parkinson＇s disease（PD）.Neuromelanin（NM） in the pre-synaptic terminal of dopamine neurons is emerging as a primary player in the etiology of neurodegenerative disorders including PD.This mini-review discusses the interactions between neuromelanin and different molecules in the synaptic terminal and describes how these interactions might affect neurodegenerative disorders including PD.Neuromelanin can reversibly bind and interact with amine containing neurotoxins,e.g.,MPTP,to augment their actions in the terminal,eventually leading to the instability and degeneration of melanin-containing neurons due to oxidative stress and mitochondrial dysfunction.In particular,neuromelanin appears to confer susceptibility to chemical toxicity by providing a large sink of iron-bound,heme-like structures in a pi-conjugated system,a system seemingly purposed to allow for stabilizing interactions including pi-stacking as well as ligand binding to iron.Given the progressive accumulation of NM with age corresponding with an apparent decrease in dopamine synthetic pathways,the immediate question of whether NM is also capable of binding dopamine,the primary functional monoamine utilized in this cell,should be raised.Despite the rather glaring implications of this finding,this idea appears not to have been adequately addressed.As such,we postulate on potential mechanisms by which dopamine might dissociate from neuromelanin and the implications of such a reversible relationship.Intriguingly,if neuromelanin is able to sequester and release dopamine in membrane bound vesicles,this intracellular pre-synaptic mechanism could be the basis for a form of chemical memory in dopamine neurons.展开更多
BACKGROUND The etiological diagnosis of intracranial hypertension is quite complicated but important in clinical practice.Some common causes are craniocerebral injury,intracranial space-occupying lesion,subarachnoid h...BACKGROUND The etiological diagnosis of intracranial hypertension is quite complicated but important in clinical practice.Some common causes are craniocerebral injury,intracranial space-occupying lesion,subarachnoid hemorrhage,and hydrocephalus.When a patient presents with intracranial hypertension,the common causes are to be considered first so that other causes would be dismissed.With the morbidity lower than 9%,neuromelanin is very rare.Common symp-toms include nerve damage symptoms,epilepsy,psychiatric symptoms,and cognitive disorders.CASE SUMMARY We present a patient with melanoma which manifested with isolated intracranial hypertension without any other neurological signs.A 22-year-old male had repeated nausea and vomiting for 2 mo with Babinski sign(+)on both sides,nuchal rigidity,and subarachnoid hemorrhage.He had been diagnosed with melanoma and was given surgery and whole-brain radiation.Ultimately,the patient died 2 mo later.CONCLUSION Malignant melanoma should be taken into consideration in the differential diagnosis of intracranial hypertension.展开更多
To investigate the effects of oxidative stress on substantia nigra neuronal degeneration and death in patients with Parkinson＇s disease, we treated neuroblastoma cells （SK-N-SH） and glioma cells with Fenton＇s reag...To investigate the effects of oxidative stress on substantia nigra neuronal degeneration and death in patients with Parkinson＇s disease, we treated neuroblastoma cells （SK-N-SH） and glioma cells with Fenton＇s reagent, iron chelating agent, neuromelanin and dopamine melanin. We investigated the changes in expression of nine oxidative stress-related genes and proteins. The levels of mRNAs for heme-oxygenase-1 and glutathione S-transferase-ml were significantly reduced in SK-N-SH cells exposed to oxidative stress, and increased in glial cells treated with deferoxamine. These results revealed that SK-N-SH neurons react sensitively to oxidative stress, which implies different outcomes between these two types of cells in the substantia nigra. Moreover, the influences of neuromelanin and dopamine melanin on cell function are varied, and dopamine melanin is not a good model for neuromelanin.展开更多
文摘The loss of pigmented neurons from the human brain has long been the hallmark of Parkinson＇s disease（PD）.Neuromelanin（NM） in the pre-synaptic terminal of dopamine neurons is emerging as a primary player in the etiology of neurodegenerative disorders including PD.This mini-review discusses the interactions between neuromelanin and different molecules in the synaptic terminal and describes how these interactions might affect neurodegenerative disorders including PD.Neuromelanin can reversibly bind and interact with amine containing neurotoxins,e.g.,MPTP,to augment their actions in the terminal,eventually leading to the instability and degeneration of melanin-containing neurons due to oxidative stress and mitochondrial dysfunction.In particular,neuromelanin appears to confer susceptibility to chemical toxicity by providing a large sink of iron-bound,heme-like structures in a pi-conjugated system,a system seemingly purposed to allow for stabilizing interactions including pi-stacking as well as ligand binding to iron.Given the progressive accumulation of NM with age corresponding with an apparent decrease in dopamine synthetic pathways,the immediate question of whether NM is also capable of binding dopamine,the primary functional monoamine utilized in this cell,should be raised.Despite the rather glaring implications of this finding,this idea appears not to have been adequately addressed.As such,we postulate on potential mechanisms by which dopamine might dissociate from neuromelanin and the implications of such a reversible relationship.Intriguingly,if neuromelanin is able to sequester and release dopamine in membrane bound vesicles,this intracellular pre-synaptic mechanism could be the basis for a form of chemical memory in dopamine neurons.
文摘BACKGROUND The etiological diagnosis of intracranial hypertension is quite complicated but important in clinical practice.Some common causes are craniocerebral injury,intracranial space-occupying lesion,subarachnoid hemorrhage,and hydrocephalus.When a patient presents with intracranial hypertension,the common causes are to be considered first so that other causes would be dismissed.With the morbidity lower than 9%,neuromelanin is very rare.Common symp-toms include nerve damage symptoms,epilepsy,psychiatric symptoms,and cognitive disorders.CASE SUMMARY We present a patient with melanoma which manifested with isolated intracranial hypertension without any other neurological signs.A 22-year-old male had repeated nausea and vomiting for 2 mo with Babinski sign(+)on both sides,nuchal rigidity,and subarachnoid hemorrhage.He had been diagnosed with melanoma and was given surgery and whole-brain radiation.Ultimately,the patient died 2 mo later.CONCLUSION Malignant melanoma should be taken into consideration in the differential diagnosis of intracranial hypertension.
基金the National Natural Science Foundation of China, No. 30600201the Tianjin Science and Technology Committee, No. 07JCYBJC09900
文摘To investigate the effects of oxidative stress on substantia nigra neuronal degeneration and death in patients with Parkinson＇s disease, we treated neuroblastoma cells （SK-N-SH） and glioma cells with Fenton＇s reagent, iron chelating agent, neuromelanin and dopamine melanin. We investigated the changes in expression of nine oxidative stress-related genes and proteins. The levels of mRNAs for heme-oxygenase-1 and glutathione S-transferase-ml were significantly reduced in SK-N-SH cells exposed to oxidative stress, and increased in glial cells treated with deferoxamine. These results revealed that SK-N-SH neurons react sensitively to oxidative stress, which implies different outcomes between these two types of cells in the substantia nigra. Moreover, the influences of neuromelanin and dopamine melanin on cell function are varied, and dopamine melanin is not a good model for neuromelanin.
