Nigrostriatal neuronal death in Parkinson’s disease — a passive or an active genetically-controlled process?

Ziv, Ilan; Barzilai, Ari; Offen, Daniel; Nardi, Nurit; Melamed, Eldad

doi:10.1007/978-3-7091-6844-8_7

Cited by 21 publications

(14 citation statements)

References 21 publications

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“…11 37 A possible mechanism linking LMM and PD may be polymorphisms in the MC3/MC4 melanocortin receptor ( MC3R , MC4R ) genes, which might alter the effect of the β-melanocyte-stimulating hormone 38 39. A number of other potential common mechanisms that deserve further exploration have been proposed earlier 4 5 8 9. Of note, the results of recent studies suggest a decreased risk of PD in outdoor workers with regular sunlight exposure of skin, which has been proposed as being the consequence of a neuroprotective effect of sunlight-induced higher vitamin D levels 40.…”

Section: Discussionmentioning

confidence: 99%

“…This implies an increased risk of PD in individuals with a history of melanoma. A number of potentially involved mechanisms have been proposed such as altered a-synuclein metabolism,5 decreased dopamine synthesis and dysregulated control of dopamine effects,8 and common central and peripheral melanogenesis mechanisms 9. However, recent studies failed to reveal an association between the risk of PD alleles and risk of melanoma,10 nor between the risk of genetic susceptibility loci for pigmentation or melanoma and risk of PD 11.…”

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confidence: 99%

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Frequency and profile of Parkinson's disease prodromi in patients with malignant melanoma

Walter

Heilmann

Voss

et al. 2015

J Neurol Neurosurg Psychiatry

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Frequency and profile of Parkinson's disease prodromi in patients with malignant melanoma

Walter

Heilmann

Voss

et al. 2015

J Neurol Neurosurg Psychiatry

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“…One view is that PD arises from damage to pcSN neurons at the nuclear level because DA is genotoxic and triggers apoptosis in neuronal cells, while Bcl-2 transfection of PC12 cells prevents apoptosis (Ziv et al, 1997a).…”

Section: Evidence For Neurotoxin-induced Apoptosismentioning

confidence: 99%

Review on apoptosis vs. necrosis of substantia nigrapars compacta in parkinson’s disease

Kostrzewa

2000

neurotox res

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The discovery that melanized neurons of the pars compacta of substantia nigra (pcSN) degenerate in the midbrain of human Parkinsonians is nearly a century old, but only in this decade have we gained insights into mechanisms underlying this neuronal loss. Although it had long been assumed that pcSN neurons underwent necrosis, recent (1) in vitro studies on isolated neurons, (2) in vivo studies in animals treated with neurotoxins, and (3) postmortem study of human Parkinsonian brain provide strong evidence that pcSN cells may be lost more from apoptosis (i.e., cell suicide) than from necrosis. This paper gives some historical perspective, but focuses primarily on mechanisms involved in both necrosis and apoptosis of neurons, primarily dopaminergic, and reviews the recent literature relating to apoptosis and apoptotic factors now identified in neurons undergoing neurotoxin-induced death and in postmortem human Parkinsonian brain. The weight of evidence in favor of apoptosis and apoptotic factors in these neurons, provides us with tools needed to develop anti-apoptotic factors that can be targeted to proteins on genes, so that it may be possible to decelerate or prevent the progressive neuronal cell loss in human Parkinsonians or in humans with other neurodegenerative disorders.

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“…Parkinson's disease (PD) is characterized by the demise of a subset of midbrain dopaminergic (DAergic) neurons in the Substantia nigra pars compacta (SNpc) (Hirsch et al 1997). The well-organized extended DAergic fibers that form the nigrostriatal (SN-ST) pathway as a chief route of dopamine circulation in the basal ganglia also disintegrate in the course of the disease (Ziv et al 1997;Lang and Obeso 2004). Indeed, PD symptoms occur when 80% of striatal dopamine and 50% of the nigral cells are lost (Riederer and Wuketich 1976).…”

Section: Introductionmentioning

confidence: 99%

Optimized Quantities of GDNF Overexpressed by Engineered Astrocytes Are Critical for Protection of Neuroblastoma Cells Against 6-OHDA Toxicity

et al. 2011

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Optimized levels of glial cell line-derived neurotrophic factor (GDNF) are critical for protection of dopaminergic neurons against parkinsonian cell death. Recombinant lentiviruses harboring GDNF coding sequence were constructed and used to infect astrocytoma cell line 1321N1. The infected astrocytes overexpressed GDNF mRNA and secreted an average of 2.2 ng/mL recombinant protein as tested in both 2 and 16 weeks post-infection. Serial dilutions of GDNF-enriched conditioned medium from infected astrocytes added to growing neuroblastoma cell line SK-N-MC resulted in commensurate resistance against 6-OHDA toxicity. SK-N-MC cell survival rate rose from 51% in control group to 84% in the cells grown with astro-CM containing 453 pg secreted GDNF, an increase that was highly significant (P < 0.0001). However, larger volumes of the GDNF-enriched conditioned medium failed to improve cell survival and addition of volumes that contained 1,600 pg or more GDNF further reduced survival rate to below 70%. Changes in cell survival paralleled to changes in the percent of apoptotic cell morphologies. These data demonstrate the feasibility of using astrocytes as minipumps to stably oversecrete neurotrophic factors and further indicate that GDNF can be applied to neuroprotection studies in PD pending the optimization of its concentrations.

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Nigrostriatal neuronal death in Parkinson’s disease — a passive or an active genetically-controlled process?

Cited by 21 publications

References 21 publications

Frequency and profile of Parkinson's disease prodromi in patients with malignant melanoma

Frequency and profile of Parkinson's disease prodromi in patients with malignant melanoma

Review on apoptosis vs. necrosis of substantia nigrapars compacta in parkinson’s disease

Optimized Quantities of GDNF Overexpressed by Engineered Astrocytes Are Critical for Protection of Neuroblastoma Cells Against 6-OHDA Toxicity

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