Evidence is mounting that the small bodies of our Solar System, such as comets and asteroids, have at least partially inherited their chemical composition from the first phases of the Solar System formation. It then appears that the molecular complexity of these small bodies is most likely related to the earliest stages of star formation. It is therefore important to characterize and to understand how the chemical evolution changes with solar-type protostellar evolution. We present here the Large Program "Astrochemical Surveys At IRAM" (ASAI). Its goal is to carry out unbiased millimeter line surveys between 80 and 272 GHz of a sample of ten template sources, which fully cover the first stages of the formation process of solar-type stars, from prestellar cores to the late protostellar phase. In this article, we present an overview of the surveys and results obtained from the analysis of the 3 mm band observations. The number of detected main isotopic species barely varies with the evolutionary stage and is found to be very similar to that of massive star-forming regions. The molecular content in O- and C- bearing species allows us to define two chemical classes of envelopes, whose composition is dominated by either a) a rich content in O-rich complex organic molecules, associated with hot corino sources, or b) a rich content in hydrocarbons, typical of Warm Carbon Chain Chemistry sources. Overall, a high chemical richness is found to be present already in the initial phases of solar-type star formation.

Chemical diversity of the gas in low-mass protostellar cores is widely recognized. In order to explore its origin, a survey of chemical composition toward 36 Class 0/I protostars in the Perseus molecular cloud complex, which are selected in an unbiased way under certain physical conditions, has been conducted with IRAM 30 m and NRO 45 m telescope. Multiple lines of C 2 H, c-C 3 H 2 and CH 3 OH have been observed to characterize the chemical composition averaged over a 1000 au scale around the protostar. The derived beam-averaged column densities show significant chemical diversity among the sources, where the column density ratios of C 2 H/CH 3 OH are spread out by 2 orders of magnitude. From previous studies, the hot corino sources have abundant CH 3 OH but deficient C 2 H, their C 2 H/CH 3 OH column density ratios being relatively low. In contrast, the warm-carbon-chain chemistry (WCCC) sources are found to reveal the high C 2 H/CH 3 OH column density ratios. We find that the majority of the sources have intermediate characters between these two distinct chemistry types. A possible trend is seen between the C 2 H/CH 3 OH ratio and the distance of the source from the edge of a molecular cloud. The sources located near cloud edges or in isolated clouds tend to have a high C 2 H/CH 3 OH ratio. On the other hand, the sources having a low C 2 H/CH 3 OH ratio tend to be located in inner regions of the molecular cloud complex. This result gives an important clue to an

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), and experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of the disease. Here, we examined the pathophysiological role of Kallikrein 6 (Klk6), a serine protease produced by oligodendrocytes (OLs), in EAE using Klk6 knockout (Klk6-/-) mice. Compared with Klk6+/+ (wild-type) mice, Klk6-/- mice showed milder EAE symptoms, including delayed onset and milder paralysis. Loss of Klk6 suppressed matrix metalloprotease-9 expression and diminished the infiltration of peripheral inflammatory cells into the CNS by decreasing blood-brain barrier (BBB) permeability and reducing expression levels of inflammatory cytokines, chemokines and their receptors. Scanning electron microscopic analysis revealed demyelination characterized by myelin detachment from the axons in the early phase of EAE progression (days 3-7) in Klk6+/+ mice but not in Klk6-/- mice. Interestingly, anti-MOG (myelin oligodendrocyte glycoprotein) autoantibody was also detected in the cerebrospinal fluid (CSF) and spinal cord on day 3 after MOG immunization. Furthermore, treatment of primary cultured OLs with anti-MOG autoantibody induced oligodendroglial morphological changes and increases in myelin basic protein and Klk6 expression. We also developed a novel enzyme-linked immunoabsorbent assay method for detecting activated KLK6 in human CSF. In human autopsy brain samples, expression of active KLK6 was detected in OLs using an antibody that specifically recognizes the protein's activated form. Taken together, our findings demonstrate that Klk6 secreted by OLs plays a critical role in the pathogenesis of EAE/MS and that it might serve as a potential therapeutic target for MS.