Oxidative stress has been implicated in the etiology of Parkinson's disease (PD) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model PD. It is known that under conditions oxidative stress, transcription factor NF-E2-related (Nrf2) binds to antioxidant response element (ARE) induce phase II detoxification enzymes. To investigate role Nrf2 process MPTP-induced toxicity, mice expressing human placental alkaline phosphatase (hPAP) gene driven by a promoter containing core ARE...

Activation of the transcription factor Nrf2 in astrocytes coordinates upregulation antioxidant defenses and confers protection to neighboring neurons. Dominant mutations Cu/Zn-superoxide dismutase (SOD1) cause familial forms amyotrophic lateral sclerosis (ALS), a fatal disorder characterized by progressive loss motor Non-neuronal cells, including astrocytes, shape neuron survival ALS are potential target prevent degeneration. The protective effect activation has never been examined chronic...

Abstract Reactive astrocytes frequently surround degenerating motor neurons in patients and transgenic animal models of amyotrophic lateral sclerosis (ALS). We report here that reactive the ventral spinal cord ALS‐mutant G93A superoxide dismutase (SOD) mice expressed nerve growth factor (NGF) regions where p75 neurotrophin receptor (p75 NTR ) were immunoreactive for nitrotyrosine. Cultured incubated with lipopolysaccharide (LPS) or peroxynitrite became accumulated NGF culture medium. caused...

Abstract Astrocytes may modulate the survival of motor neurons in amyotrophic lateral sclerosis (ALS). We have previously shown that fibroblast growth factor‐1 (FGF‐1) activates astrocytes to increase secretion nerve factor (NGF). NGF turn induces apoptosis co‐cultured expressing p75 neurotrophin receptor (p75 NTR ) by a mechanism involving nitric oxide (NO) and peroxynitrite formation. show here FGF‐1 increased expression inducible synthase NO production astrocytes, making adjacent...

Alpha synuclein (SYN) is a central player in the pathogenesis of sporadic and familial Parkinson's disease (PD). SYN aggregation oxidative stress are associated enhance each other's toxicity. It unknown whether redox-sensitive transcription factor nuclear erythroid 2-related 2 (Nrf2) plays role against toxicity SYN. To examine this, mice selectively overexpressing Nrf2 astrocytes (GFAP-Nrf2) were crossed with expressing human mutant (hSYN A53T ) neurons. Increased astrocytic delayed onset...

Nicotinamide adenine dinucleotide (NAD(+)) participates in redox reactions and NAD(+)-dependent signaling pathways. Although the are critical for efficient mitochondrial metabolism, they not accompanied by any net consumption of nucleotide. On contrary, processes lead to its degradation. Three distinct families enzymes consume NAD(+) as substrate: poly(ADP-ribose) polymerases, ADP-ribosyl cyclases (CD38 CD157), sirtuins (SIRT1-7). Because all above generate nicotinamide a byproduct,...

Fibroblast growth factor-1 (FGF-1) is highly expressed in motor neurons and can be released response to sublethal cell injury. Because FGF-1 potently activates astroglia exerts a direct neuroprotection after spinal cord injury or axotomy, we examined whether it regulated the expression of inducible cytoprotective heme oxygenase-1 (HO-1) enzyme astrocytes. induced HO-1 cultured rat astrocytes, which was dependent on FGF receptor activation prevented by cycloheximide. also Nrf2 mRNA protein...

Nerve growth factor (NGF) can induce apoptosis by signaling through the p75 neurotrophin receptor (p75 NTR ) in several nerve cell populations. Cultured embryonic motor neurons expressing are not vulnerable to NGF unless they exposed an exogenous flux of nitric oxide ( • NO). In present study, we show that -mediated involved neutral sphingomyelinase activation, increased mitochondrial superoxide production, and cytochrome c release cytosol. The mitochondria-targeted antioxidants mitoQ mitoCP...

Abstract Fibroblast growth factor‐1 (FGF1 or acidic FGF) is highly expressed in motor neurons. FGF‐1 released from cells by oxidative stress, which might occur SOD‐1 aberrant function amyotrophic lateral sclerosis (ALS). Although known to be neuroprotective after spinal cord injury axotomy, we found that could activate astrocytes a manner decreased neuron survival co‐cultures. induced accumulation of the FGF receptor 1 (FGFR1) astrocyte nuclei and potently stimulated nerve factor (NGF)...

Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motor neurons. Astrocytes from diverse ALS models induce neuron death in co-culture. Enhancing NAD+ availability, or increasing the expression NAD+-dependent deacylases SIRT3 and SIRT6, abrogates their neurotoxicity cell culture models. To determine effect availability mouse we used two strategies, ablation a NAD+-consuming enzyme (CD38) supplementation with bioavailable precursor (nicotinamide riboside, NR)....

Nuclear factor E2-related 2 (Nrf2) is a transcription that known to regulate variety of cytoprotective genes through the antioxidant response element (ARE). This endogenous one major pathways by which cells are protected from xenobiotic or innate oxidative insults. Furthermore, in neural systems, astrocyte-specific activation Nrf2 protect neurons. In previous work, our laboratory found protects intrastriatal injections mitochondrial complex II inhibitor malonate. Here, we extend these...

Abstract Fatty acid binding proteins (FABPs) are key regulators of lipid metabolism, energy homeostasis, and inflammation. They participate in fatty metabolism by regulating their uptake, transport, availability ligands to nuclear receptors. In the adult brain, FABP7 is especially abundant astrocytes that rich cytoplasmic granules originated from damaged mitochondria. Mitochondrial dysfunction oxidative stress have been implicated neurodegenerative process observed amyotrophic lateral...

Sirtuins (SIRTs) are NAD+-dependent deacylases that play a key role in transcription, DNA repair, metabolism, and oxidative stress resistance. Increasing NAD+ availability regulates endogenous SIRT activity, leading to increased resistance decreased mitochondrial reactive oxygen production multiple cell types disease models. This protection, at least part, depends on the activation of antioxidant proteins. We now show increasing total content astrocytes leads transcription factor nuclear...

Abstract Alzheimer’s disease (AD), the most common cause of dementia in elderly, is characterized by accumulation intracellular neurofibrillary tangles, extracellular amyloid plaques, and neuroinflammation. In partnership with microglial cells, astrocytes are key players regulation Fatty acid binding protein 7 (FABP7) belongs to a family conserved proteins that regulate lipid metabolism, energy homeostasis, inflammation. FABP7 expression largely restricted radial glia-like cells adult...