Paper with drawings! "Peroxisome Proliferator-Activated Receptor (PPAR) γ and PPARα Agonists Modulate Mitochondrial Fusion-Fission Dynamics: Relevance to Reactive Oxygen Species (ROS)-Related Neurodegenerative Disorders?"

Peroxisome Proliferator-Activated Receptor (PPAR) γ and PPARα Agonists Modulate Mitochondrial Fusion-Fission Dynamics: Relevance to Reactive Oxygen Species (ROS)-Related Neurodegenerative Disorders?

Zolezzi JM, Silva-Alvarez C, Ordenes D, Godoy JA, Carvajal FJ, Santos MJ, Inestrosa NC.

Recent studies showed that the activation of the retinoid X receptor, which dimerizes with peroxisome proliferator-activated receptors (PPARs), leads to an enhanced clearance of Aβ from the brain of transgenic mice model of Alzheimer's disease (AD), because an increased expression of apolipoprotein E and it main transporters. However, the effects observed must involve additional underlying mechanisms that have not been yet explored. Several studies conducted in our laboratory suggest that part of the effects observed for the PPARs agonist might involves mitochondrial function and, particularly, mitochondrial dynamics. In the present study we assessed the effects of oxidative stress challenge on mitochondrial morphology and mitochondrial dynamics-related proteins in hippocampal neurons. Using immunofluorescence, we evaluated the PPARγ co-activator 1α (PGC-1α), dynamin related protein 1 (DRP1), mitochondrial fission protein 1 (FIS1), and mitochondrial length, in order to determine if PPARs agonist pre-treatment is able to protect mitochondrial population from hippocampal neurons through modulation of the mitochondrial fusion-fission events. Our results suggest that both a PPARγ agonist (ciglitazone) and a PPARα agonist (WY 14.643) are able to protect neurons by modulating mitochondrial fusion and fission, leading to a better response of neurons to oxidative stress, suggesting that a PPAR based therapy could acts simultaneously in different cellular components. Additionally, our results suggest that PGC-1α and mitochondrial dynamics should be further studied in future therapy research oriented to ameliorate neurodegenerative disorders, such as AD.

Paper published

Kidney

New models and new tissues !

mmmm? why so serious ??

Review: Wnt Signaling Roles on the Structure and Function of the Central Synapses: Involvement in Alzheimer’s Disease

Review with drawings accepted !  Click Review Here !!

This is a old version of drawings of Graphique-science, but now are coming new versions!

 Wnts compromise a large family of secreted glycoproteins that have shown to be part of the signaling molecules that regulate several aspects of development such as axis formation and midbrain development [1, 2]. In mammals at least 19 Wnt members have been found. The interaction of a Wnt protein with members of the Frizzled (Fz) family of seven-pass transmembrane cell-surface receptors triggers the activation of the Wnt signaling pathway . In human and mice, 10 members of the Fz family have been identified. In addition, receptor-like tyrosine kinase (Ryk) and receptor tyrosine kinase-like orphan receptor (Ror2) have been identified as alternative Wnt receptors [6-8]. Different Wnt signaling cascades are activated downstream the Wnt receptors, identified as Wnt/β-catenin or canonical pathway, and β-catenin-independent or non-canonical pathways. The canonical pathway involves the transcription of Wnt target genes, while activation of non-canonical Wnt pathways may induce either an increase in intracellular calcium concentration or activation of the c-Jun-N-terminal kinase (JNK) cascade.

New drawing model of a Signaling by Graphique-science

A couple of weeks ago, I was looking for a new design of drawings. So now, here is my new style of creations !!. More definition and more design with a new concept. Enjoy !  I will accept observations !.

Neurogenesis Re-Loaded !!

Neurogenesis in the Sub-Granular Zone (SGZ) of the hippocampus Reloaded!!. This drawing was created in comparison with one of my firsts design in the neurogenesis. Thanks to the creativity and patience to make everyday a nice work !

(Hace un tiempo había realizado este dibujo pero sin los conocimientos que he ido adquiriendo en el tiempo. Hoy año 2013 Graphique-science esta a la vanguardia!!!)

First drawing in a review !!

http://link.springer.com/article/10.1007%2Fs12035-013-8435-5

Peroxisome Proliferator-activated Receptors and Alzheimer's Disease: Hitting the Blood–Brain Barrier  

Juan M. Zolezzi and Nibaldo C. Inestrosa

The blood–brain barrier (BBB) is often affected in several neurodegenerative disorders, such as Alzheimer's disease (AD). Integrity and proper functionality of the neurovascular unit are recognized to be critical for maintenance of the BBB. Research has traditionally focused on structural integrity more than functionality, and BBB alteration has usually been explained more as a consequence than a cause. However, ongoing evidence suggests that at the early stages, the BBB of a diseased brain often shows distinct expression patterns of specific carriers such as members of the ATP-binding cassette (ABC) transport protein family, which alter BBB traffic. In AD, amyloid-β (Aβ) deposits are a pathological hallmark and, as recently highlighted by Cramer et al. (2012), Aβ clearance is quite fundamental and is a less studied approach. Current knowledge suggests that BBB traffic plays a more important role than previously believed and that pharmacological modulation of the BBB may offer new therapeutic alternatives for AD. Recent investigations carried out in our laboratory indicate that peroxisome proliferator-activated receptor (PPAR) agonists are able to prevent Aβ-induced neurotoxicity in hippocampal neurons and cognitive impairment in a double transgenic mouse model of AD. However, even when enough literature about PPAR agonists and neurodegenerative disorders is available, the problem of how they exert their functions and help to prevent and rescue Aβ-induced neurotoxicity is poorly understood. In this review, along with highlighting the main features of the BBB and its role in AD, we will discuss information regarding the modulation of BBB components, including the possible role of PPAR agonists as BBB traffic modulators.