5 documents found, page 1 of 1
Differential lipid composition and regulation along the hippocampal longitudina...
Miranda, André Miguel; Bravo, Ana Francisca Rodrigues Vaz; Chan, Robin B.; Sousa, Nuno; Di Paolo, Gilbert; Oliveira, Tiago GilLipids are major constituents of the brain largely implicated in physiological and pathological processes. The hippocampus is a complex brain structure involved in learning, memory and emotional responses, and its functioning is also affected in various disorders. Despite conserved intrinsic circuitry, behavioral and anatomical studies suggest the existence of a structural and functional gradient along the hipp...
Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragm...
Miranda, André Miguel Lopes; Lasiecka, Zofia M.; Xu, Yimeng; Neufeld, Jessi; Shahriar, Sanjid; Simoes, Sabrina; Chan, Robin B.; Oliveira, Tiago GilDefects in endolysosomal and autophagic functions are increasingly viewed as key pathological features of neurodegenerative disorders. A master regulator of these functions is phosphatidylinositol-3-phosphate (PI3P), a phospholipid synthesized primarily by class III PI 3-kinase Vps34. Here we report that disruption of neuronal Vps34 function in vitro and in vivo impairs autophagy, lysosomal degradation as well ...
The impact of chronic stress on the rat brain lipidome
Oliveira, Tiago Gil; Chan, Robin B.; Bravo, F. V.; Miranda, A. S.; Silva, R. R.; Zhou, B.; Marques, Fernanda; Pinto, V.; Cerqueira, João JoséChronic stress is a major risk factor for several human disorders that affect modern societies. The brain is a key target of chronic stress. In fact, there is growing evidence indicating that exposure to stress affects learning and memory, decision making and emotional responses, and may even predispose for pathological processes, such as Alzheimer's disease and depression. Lipids are a major constituent of the...
Comparative lipidomic analysis of mouse and human brain with Alzheimer disease
Chan, Robin B.; Oliveira, Tiago Gil; Cortes, Etty P.; Honig, Lawrence S.; Duff, Karen E.; Small, Scott A.; Wenk, Markus R.; Shui, GuanghouLipids are key regulators of brain function and have been increasingly implicated in neurodegenerative disorders including Alzheimer disease (AD). Here, a systems-based approach was employed to determine the lipidome of brain tissues affected by AD. Specifically, we used liquid chromatography-mass spectrometry to profile extracts from the prefrontal cortex, entorhinal cortex, and cerebellum of late-onset AD (LO...
Phospholipase d2 ablation ameliorates Alzheimer's disease-linked synaptic dysfu...
Oliveira, Tiago Gil; Chan, Robin B.; Tian, Huasong; Laredo, Mikael; Shui, Guanghou; Staniszewski, Agnieszka; Zhang, Hong; Wang, Lili; Kim, Tae-WanGrowing evidence implicates aberrant lipid signaling in Alzheimer's disease (AD). While phospholipases A2 and C have been recently shown to mediate key actions of amyloid ß-peptide (Aß) through a dysregulation of arachidonic acid and phosphatidylinositol-4,5-bisphosphate metabolism, respectively, the role of phospholipase D (PLD) has so far remained elusive. PLD produces phosphatidic acid (PA), a bioactive lipi...