Programmed Death-1 (PD-1, CD279) is a type I transmembrane protein belonging to the CD28/CTLA-4 family of immunoreceptors that mediate signals for regulating immune responses. Members of the CD28/CTLA-4 family have been shown to either promote T cell activation (CD28 and ICOS) or downregulate T cell activation (CTLA-4 and PD-1). CD279 is expressed on activated T-cells, B-cells, myeloid cells and on a subset of thymocytes. In vitro, ligation of CD279 inhibits TCR-mediated T-cell proliferation and production of IL-1, IL-4, IL-10 and IFN-γ. In addition, CD279 ligation also inhibits BCR mediated signaling. CD279 deficient mice have a defect in peripheral tolerance and spontaneously develop autoimmune diseases.
Among the familial mutations of α-synuclein in Parkinson′s disease, E46K has the greatest potential to aggregate. This mutation is a 188G-A tran-sition resulting in a Glu46-to-Lys (E46K) substitution in the amino-terminal region of the protein.
