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Goetz and colleagues carried out a double-blind placebo-controlled crossover study to investigate ALC at the maximal permitted dose of 45 mg/kg/day for a week on 10 patients with Huntingtons disease [61]

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The details of the Tcell activation pathways have been reviewed extensively elsewhere.23, 24, 25, 26, 27, 28 Although other members of the PKC family can also be found in the immunological synapse of different Tcell subsets,29 PKC is the most prominently studied PKC in TCR signalling since the discovery of its selective recruitment to the immunological synapse in effector T cells.30 Furthermore, it is selectively expressed in T cells within the haematopoietic cell population.31 Upon TCR activation, PKC localizes to the central supramolecular activation cluster of the immunological synapse at the plasma membrane.32 The membrane translocation of PKC requires association with costimulatory molecule CD28 with the V3 domain of PKC .33, 34, 35 The ability of PKC to segregate correctly to the central supramolecular activation cluster is dependent on the presence of CD28 as activated T cells from CD28deficient mice were unable to form the mature immunological synapse with PKC , forming a diffuse pattern throughout the synapse instead.33 The specific localization of PKC to the immunological synapse is critical for an effective Tcell activation and this translocated PKC is also enzymatically active.30 Interestingly, the activity of PKC is also regulated by the intracellular redox state, in which the oxidized inactive form of PKC is recruited to the plasma membrane in naive T cells.36 The role of PKC in regulating Tcell function was initially characterized using PKC knockout mice (Table 1).37, 38, 39 Further studies on PKC deficient T cells reveal that PKC performs different functions depending on the Tcell subpopulations

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