Despite the human brain being made of nearly 60% fat, the vast majority of studies on the mechanisms of neuronal communication which underpin cognition, memory and learning, primarily focus on proteins and/or (epi)genetic mechanisms. Phospholipids are the main component of all cellular membranes and function as substrates for numerous phospholipid-modifying enzymes, including phospholipases, which release free fatty acids (FFAs) and other lipid metabolites that can alter the intrinsic properties of the membranes, recruit and activate critical proteins, and act as lipid signalling molecules. Here, we will review brain specific phospholipases, their roles in membrane remodelling, neuronal function, learning and memory, as well as their disease implications. In particular, we will highlight key roles of unsaturated FFAs, particularly arachidonic acid, in neurotransmitter release, neuroinflammation and memory. In light of recent findings, we will also discuss the emerging role of phospholipase A1 and the creation of saturated FFAs in the brain.

: Exosomes are nano-membrane vesicles that various cell types secrete during physiological and pathophysiological conditions. By shuttling bioactive molecules such as nucleic acids, proteins, and lipids to target cells, exosomes serve as key regulators for multiple cellular processes, including cancer metastasis. Recently, microvesicles have emerged as a challenge in the treatment of prostate cancer (PCa), encountered either when the number of vesicles increases or when the vesicles move into circulation, potentially with an ability to induce drug resistance, angiogenesis, and metastasis. Notably, the exosomal cargo can induce the desmoplastic response of PCa-associated cells in a tumor microenvironment (TME) to promote PCa metastasis. However, the crosstalk between PCaderived exosomes and the TME remains only partially understood. In this review, we provide new insights into the metabolic and molecular signatures of PCa-associated exosomes in reprogramming the TME, and the subsequent promotion of aggressive phenotypes of PCa cells. Elucidating the molecular mechanisms of TME reprogramming by exosomes draws more practical and universal conclusions for the development of new therapeutic interventions when considering TME in the treatment of PCa patients.

NULL

NULL

NULL

NULL

NULL

NULL

NULL

NULL