Furthermore, transfected NSC were used for delivery of neurotrophic factors in Alzheimer’ disease mouse model. Our earlier studies suggest cell-carriers offer distinct advantages over standard drug administration regimens by providing diseasespecific homing, sustained on site drug delivery, and improved therapeutic efficacy. Based on our previously developed cell-mediated drug delivery system, present work utilized genetically-modified autologous macrophages for active targeted delivery of GDNF to the LEE011 inflamed brain. The overall scheme of these investigations is depicted in Figure 1. Macrophages were transfected ex vivo to produce GDNF, and administered intravenously in mice with PD model. This resulted in significant increases in dopaminergic neurons survival and decreases in inflammation in SNpc. Of note, genetically-modified macrophages released exosomes with incorporated GDNF that may facilitate GDNF transport into the target cells and preserve it against degradation. Exosomes are nanosized vesicles secreted by a variety of cells, in particular, cells of the immune system: dendritic cells, macrophages, B cells, and T cells. These extracellular vesicles were initially thought to be a mechanism for removing unneeded proteins. Recent studies revealed, they are actually specialized in long-distance intercellular communications facilitating transfer of proteins, functional mRNAs and microRNAs for subsequent protein expression in target cells. To shuttle their cargo, exosomes can attach by a range of surface adhesion proteins and specific vector ligands, and fuse with target cellular membranes delivering their payload. Indeed, exosomes, comprised of cellular membranes, have an exceptional ability to interact with target cells. Thus, we demonstrated here that exosomes showed an extraordinary ability to abundantly adhere and overflow neuronal cells as was visualized by confocal microscopy. This mechanism may play a significant role in GDNF-mediated protection effects, increasing the blood circulation time, reducing immunogenicity, and facilitation of the protein transfer across the BBB and into target neurons. In addition, the membranotropic properties of GDNF-carrying exosomes may facilitate GDNF binding to GFRa-1 receptors expressed on DA neurons. The present data indicate, intrinsic properties of macrophages can overcome the limitations of current common therapies, alleviate and reverse the symptoms, and may ultimately improve the quality of life of patients with various neurodegenerative disorders. Obesity contributes to the aetiology of common associated metabolic diseases. The causes of obesity are multifactorial, with environmental and genetic components. Westernized lifestyle, with high-caloric diets and a lack of physical exercise, is an obvious factor of obesity, but obesity does not develop in all individuals exposed to an obesogenic environment.