Corrigendum to "PPARs in Human Neuroepithelial Tumors: PPAR Ligands as Anticancer Therapies for the Most Common Human Neuroepithelial Tumors".

[This corrects the article DOI: 10.1155/2010/427401.].

Targeting PPARalpha in Alzheimer's Disease.

Background: The molecular mechanisms underlying Alzheimer's disease (AD) are yet to be fully elucidated. The so-called "amyloid cascade hypothesis" has long been the prevailing paradigm for causation of disease, and is today being revisited in relation to other pathogenic pathways, such as oxidative stress, neuroinflammation and energy dysmetabolism. The peroxisome proliferator-activated receptors (PPARs) are expressed in the central nervous system (CNS) and regulate many physiological processes, such as energy metabolism, neurotransmission, redox homeostasis, autophagy and cell cycle.

Roles of PPAR transcription factors in the energetic metabolic switch occurring during adult neurogenesis.

PPARs are a class of ligand-activated transcription factors belonging to the superfamily of receptors for steroid and thyroid hormones, retinoids and vitamin D that control the expression of a large number of genes involved in lipid and carbohydrate metabolism and in the regulation of cell proliferation, differentiation and death. The role of PPARs in the CNS has been primarily associated with lipid and glucose metabolism; however, these receptors are also implicated in neural cell differentiation and death, as well as neuronal maturation. Although it has been demonstrated that PPARs play important roles in determining NSCs fate, less is known about their function in regulating NSCs metabolism during differentiation.

Oxidative Stress during the Progression of β-Amyloid Pathology in the Neocortex of the Tg2576 Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive neurodegeneration. Pathogenetic mechanisms, triggered by β-amyloid (Aβ) accumulation, include oxidative stress, derived from energy homeostasis deregulation and involving mitochondria and peroxisomes. We here addressed the oxidative stress status and the elicited cellular response at the onset and during the progression of Aβ pathology, studying the neocortex of Tg2576 model of AD.

Neuroprotective properties of peroxisome proliferator-activated receptor alpha (PPARα) and its lipid ligands.

Signalling lipids are known to control a wide array of cellular processes, including cell proliferation, apoptosis, migration, and energy metabolism. Fatty acids and their derivatives, eicosanoids, phosphoinositides, sphingolipids, some cannabinoid-like molecules bind and activate nuclear receptors, including peroxisome proliferator-activated receptors (PPARs). This subfamily of transcription factors comprises three isotypes - PPARα (NR1C1), PPAR β/δ (NR1C2), PPARγ (NR1C3) - which bind to specific DNA response elements, as heterodimers with retinoid X receptors.

Age-dependent roles of peroxisomes in the hippocampus of a transgenic mouse model of Alzheimer's disease.

Background: Alzheimer's Disease (AD) is a progressive neurodegenerative disease, especially affecting the hippocampus. Impairment of cognitive and memory functions is associated with amyloid β-peptide-induced oxidative stress and alterations in lipid metabolism. In this scenario, the dual role of peroxisomes in producing and removing ROS, and their function in fatty acids β-oxidation, may be critical.

Hypoxia induces peroxisome proliferator-activated receptor α (PPARα) and lipid metabolism peroxisomal enzymes in human glioblastoma cells.

Glioblastoma multiforme (GBM) represents the most severe type of glioma, the most common brain tumor. Their malignancy shows a relationship with an increased proliferation and a poorly organized tumor vascularization, an event that leads to inadequate blood supply, hypoxic areas and at last to the formation of necrotic areas, a feature of glioblastoma. Hypoxic/necrotic tumors are more resistant to chemotherapy and radiation therapies, thus it is crucial to formulate new therapeutic approaches that can render these tumors more sensitive to the action of conventional therapies.

Signal transduction pathways involved in PPARβ/δ-induced neuronal differentiation.

Neuroblastomas are pediatric tumors originating from neuroblasts in the developing peripheral nervous system. The neurotrophin brain-derived neurotrophic factor (BDNF) is a key regulator of survival and differentiation of specific neuronal populations in the central and peripheral nervous system. Patients whose neuroblastoma tumors express high levels of BDNF and TrkB have an unfavorable prognosis.

Lipid metabolism impairment in human gliomas: expression of peroxisomal proteins in human gliomas at different grades of malignancy.

Gliomas are histologically graded by cellularity, cytological atypia, necrosis, mitotic figures, and vascular proliferation, features associated with biologically aggressive behaviour. However, abundant evidence suggests the presence of unrecognized, clinically relevant subclasses of the diffuse gliomas, both in respect to their underlying molecular phenotype and their clinical response to therapy. It is well-known that patient prognosis and therapeutic decisions rely on accurate pathological grading.

PPARs in Human Neuroepithelial Tumors: PPAR Ligands as Anticancer Therapies for the Most Common Human Neuroepithelial Tumors.

Neuroepithelial tumors represent a heterogeneous class of human tumors including benignant and malignant tumors. The incidence of central nervous system neoplasms ranges from 3.8 to 5.

p73 and p63 regulate the expression of fibroblast growth factor receptor 3.

p53, p63 and p73 make a family of transcription factors that play a vital role in development and cancer. All p53 family members have more than one promoter producing Transactivating (TA) and Dominant Negative (DeltaN) isoforms and their mRNAs are subjected to extensive splicing at 3' end to produce multiple protein products. p53 is usually inactivated by point mutations during tumorigenesis, whereas the expression levels and p63 and p73 are modulated to give tumor cells a selective advantage.

Early biochemical and morphological modifications in the brain of a transgenic mouse model of Alzheimer's disease: a role for peroxisomes.

The central role of peroxisomes in reactive oxygen species and lipid metabolism and their importance in brain functioning are well established. The aim of this work has been to study the peroxisomal population in the Tg2576 mouse model of Alzheimer's disease (AD), at the age of three months when no apparent signs of behavioral, neuroanatomical, cytological, or biochemical alterations have been so far described. The expression and localization of peroxisomal (PMP70, CAT, AOX, and THL) and peroxisome-related proteins (PEX5p, GPX1, SOD1, and SOD2) were studied in the neocortex and hippocampus of transgenic and wild-type animals.

Neuronal response of peroxisomal and peroxisome-related proteins to chronic and acute Abeta injury.

The central role of peroxisomes in ROS and lipid metabolism and their importance in brain functioning are well established. The aim of this work was to study the modulation of peroxisomal and peroxisome-related proteins in cortical neurons in vitro challenged with chronic or acute Abeta treatment, in order to investigate whether peroxisomes represent one of the cellular target of Abeta in these cells. The expression of peroxisomal (PMP70, catalase, acyl-CoA oxidase and thiolase), peroxisome-related (PPARalpha, insulin-degrading enzyme) and anti-oxidant (SOD1, SOD2, GSTP1) proteins was studied.

Emerging roles of peroxisome proliferator-activated receptors (PPARs) in the regulation of neural stem cells proliferation and differentiation.

The molecular mechanisms controlling the specification of neural cell fates have been the focus of intense research in recent years. Neural precursor cells (NPCs) sequentially undergo expansion, neurogenic and gliogenic fates during development, but the underlying mechanisms are poorly understood. Recent studies have identified a number of extrinsic factors that regulate the fate of NPCs.

Neuroendocrine transdifferentiation induced by VPA is mediated by PPARgamma activation and confers resistance to antiblastic therapy in prostate carcinoma.

Background: Prostate cancer (PCa) is the most commonly diagnosed cancer in men in the Western Countries. When prostatectomy fails to eradicate the primary tumor, PCa is generally refractory to all therapeutic approaches. Valproic acid (VPA) is a promising anticancer agent recently assigned to the class of histone deacetylase (HDAC) inhibitors.

PPARs Expression in Adult Mouse Neural Stem Cells: Modulation of PPARs during Astroglial Differentiaton of NSC.

PPAR isotypes are involved in the regulation of cell proliferation, death, and differentiation, with different roles and mechanisms depending on the specific isotype and ligand and on the differentiated, undifferentiated, or transformed status of the cell. Differentiation stimuli are integrated by key transcription factors which regulate specific sets of specialized genes to allow proliferative cells to exit the cell cycle and acquire specialized functions. The main differentiation programs known to be controlled by PPARs both during development and in the adult are placental differentiation, adipogenesis, osteoblast differentiation, skin differentiation, and gut differentiation.

PPARbeta agonists trigger neuronal differentiation in the human neuroblastoma cell line SH-SY5Y.

Neuroblastomas are pediatric tumors originating from immature neuroblasts in the developing peripheral nervous system. Differentiation therapies could help lowering the high mortality due to rapid tumor progression to advanced stages. Oleic acid has been demonstrated to promote neuronal differentiation in neuronal cultures.

Effects of stratospheric radiations on human glioblastoma cells.

The aim of this work was to evaluate the effect of stratospheric radiations on neural tumour cells. ADF human glioblastoma cells were hosted on a stratospheric balloon within the 2002 biological experiment campaign of the Italian Space Agency. The flight at an average height of 37 km lasted about 24 hrs.

PPARgamma-dependent effects of conjugated linoleic acid on the human glioblastoma cell line (ADF).

Conjugated linoleic acid (CLA) has been shown to exert beneficial effects against carcinogenesis, atherosclerosis and diabetes. It has been demonstrated that CLA modulates lipid metabolism through the activation of peroxisome proliferator-activated receptors (PPARs). The PPAR family comprises 3 closely related gene products, PPAR alpha, beta/delta and gamma, differing for tissue distribution, developmental expression and ligand specificity.

Immunolocalization of peroxisome proliferator-activated receptors and retinoid X receptors in the adult rat CNS.

Peroxisome proliferator-activated and retinoid X receptors (PPARs and RXRs) are transcription factors belonging to the steroid hormone receptor superfamily. Upon activation by their ligands, PPARs and RXRs bind to their target genes as heterodimers. Ligands of these receptors include lipophylic molecules, such as retinoids, fatty acids and eicosanoids, the importance of which in the metabolism and functioning of the nervous tissue is well documented.

Scavenging system efficiency is crucial for cell resistance to ROS-mediated methylglyoxal injury.

Methylglyoxal is a reactive dicarbonyl compound endogenously produced mainly from glycolytic intermediates. Recent research indicates that methylglyoxal is a potent growth inhibitor and genotoxic agent. The antiproliferative activity of methylglyoxal has been investigated for pharmacological application in cancer chemotherapy.