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

Abstract

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.

Novel mechanisms and approaches in the study of neurodegeneration and neuroprotection. A review

“…No changes were observed in mRNA levels of cyclins E, F, G1, G2, H or I nor cyclin-dependent kinases. The up-regulation of cell cycle molecules during necrosis has been reported previously (Freeman et al, 1994), and inhibitors of cyclin dependent kinases (CKKs) are known to protect against neuronal death (Park et al, 1997;2000).…”

“…In Parkinson's disease (PD) the role of neuromelanin as either an accelerant to neurotoxicity or as a neuroprotectant for pars compacta dopaminergic neurons is unresolved (Wilczok et al, 1999;Chiueh et al, 2000;Gerlach et al, 2000;Kostrzewa, 2000;Solano et al, 2000;Sulzer and Zecca, 2000;Double et al, 2003). Neuromelanin-containing neurons are apparently more susceptible to cell death (Marsden, 1983).…”

Toxicity of Luminescent Silica Nanoparticles to Living Cells

“…It is possible that cell death can be caused by less genome damage but more cellular organelle destruction (28). Genotoxicity is associated with apoptosis that is initiated by complex regulation (interconnected signaling mechanisms) (33,34), whereas cellular toxicity, such as necrosis in this study, may be directly caused by membrane lipid peroxidation, energy depletion, ROS production, and cytosolic organelle destruction (28,35). However, despite being considered of low genotoxicity, accumulated silica may induce chronic or acute toxicity if one is exposed to high concentrations of silica over a long period of time (29,36,37).…”

Apoptosis of Breast Cancer Cells: Modulation of Genes for Glycoconjugate Biosynthesis and Targeted Drug Delivery

“…In contrast, the process of necrosis in cancer cells is a progressive disintegration of cells, which affect nearby viable cells to disintegrate. Viable cells discriminate apoptosis and necrosis targets via distinct cell surface receptors (Weedon et al 1979 ;Kostrzewa 2000 ;Blagosklonny 2000 ;Patel et al 2009 ) .…”