Drug targets in Leishmania

Leishmaniasis is a major public health problem and till date there are no effective vaccines available. The control strategy relies solely on chemotherapy of the infected people. However, the present repertoire of drugs is limited and increasing resistance towards them has posed a major concern. The first step in drug discovery is to identify a suitable drug target. The genome sequences of Leishmania major and Leishmania infantum has revealed immense amount of information and has given the opportunity to identify novel drug targets that are unique to these parasites. Utilization of this information in order to come up with a candidate drug molecule requires combining all the technology and using a multi-disciplinary approach, right from characterizing the target protein to high throughput screening of compounds. Leishmania belonging to the order kinetoplastidae emerges from the ancient eukaryotic lineages. They are quite diverse from their mammalian hosts and there are several cellular processes that we are getting to know of, which exist distinctly in these parasites. In this review, we discuss some of the metabolic pathways that are essential and could be used as potential drug targets in Leishmania

The effects of electrical microstimulation on cortical signal propagation

Electrical stimulation has been used in animals and humans to study potential causal links between neural activity and specific cognitive functions. Recently, it has found increasing use in electrotherapy and neural prostheses. However, the manner in which electrical stimulation–elicited signals propagate in brain tissues remains unclear. We used combined electrostimulation, neurophysiology, microinjection and functional magnetic resonance imaging (fMRI) to study the cortical activity patterns elicited during stimulation of cortical afferents in monkeys. We found that stimulation of a site in the lateral geniculate nucleus (LGN) increased the fMRI signal in the regions of primary visual cortex (V1) that received input from that site, but suppressed it in the retinotopically matched regions of extrastriate cortex. Consistent with previous observations, intracranial recordings indicated that a short excitatory response occurring immediately after a stimulation pulse was followed by a long-lasting inhibition. Following microinjections of GABA antagonists in V1, LGN stimulation induced positive fMRI signals in all of the cortical areas. Taken together, our findings suggest that electrical stimulation disrupts cortico-cortical signal propagation by silencing the output of any neocortical area whose afferents are electrically stimulated