peroxisome disorders and peroxisome proliferator activated receptors: a rreview study to update molecular aspects of pex genes

in this presentation, we review briefly on biogenesis of peroxisomes with regard to the recent findings on biogenesis. peroxisomes perform a range of various functions as oxidation of very long chain fatty acids, generation and removal of hydrogen peroxide, while peroxisomes have also been implicated in β-oxidation of aromatic and cyclic compounds, synthesis of plasmalogens, isoprenoids, lysine and glycine betaine, metabolism of purines and pyrimidines, and catabolism of polyamines, d-amino acids and methanol.  moreover peroxisomes are participated in signaling and developmental pathways. disruption of those functions in human leads to severe disorders, mainly cause death several weeks after the birth. peroxisome biogenesis disorders (pbds) are caused by defects in import of peroxisome matrix proteins and biosynthesis of peroxisomal membrane proteins.  thus the proper function of peroxisome needs a well performance of a series of events that result in correct biogenesis and assembly of peroxisome. a number of genes have been identified which are responsible for peroxisome biogenesis termed pex genes which encoded functional proteins (pex) required for the event of peroxisome formation in the cells. thirty two pex genes have so far been identified. among these genes, pex11β, a peroxisomal membrane elongation factor, is involved in regulation of size, shape and number of peroxisomes. to investigate role of pex11β in neural differentiation of mouse embryonic stem cells (mescs), we generated a stably transduced mescs line that derives expression of a shrna against pex11β gene following doxycycline (dox) induction. knock-down of pex11β, during neural differentiation, significantly reduced expression of neural progenitor cells (npcs) and mature neuronal markers. interestingly, pretreatment of the cell with peroxisome proliferator-activated receptor γ (pparγ) agonist (pioglitazone) ameliorated the inhibitory effects of pex11β knock down on neural differentiation. pioglitazone also significantly increased expression of neural progenitor and mature neuronal markers besides the expression of peroxisomal genes in transduced mesc. the observation that pioglitazone recovered peroxisomal function, improved neural differentiation of pex11β knocked-down mescs, proposes a potential new pharmacological implication of pioglitazone for neurogenesis in patients with peroxisomal defects.