The Aβ plaque-specific

mE8 antibody might be an attractive candidate therapy to consider for secondary prevention trials for individuals with preclinical AD as well as for treatments of individuals with very mild dementia due to AD. Since those with preclinical AD and mild cognitive impairment or very mild dementia MDV3100 ic50 due to AD already have substantial Aβ deposition in their brain (Jack et al., 2010; Perrin et al., 2009), this type of treatment targeting pre-existing Aβ plaques might be quite promising as a disease modifying treatment. D.M.H. is a cofounder and on the Scientific Advisory Board of C2N Diagnostics. In the last year, he served as a neuroscience therapeutic area Scientific Advisor to Pfizer. “
“Neurons are some of the most complex and highly polarized cells in our body. Their complex dendritic morphologies underlie their ability to integrate synaptic inputs. For this reason, the mechanisms that drive dendritic morphogenesis have been extensively

studied over recent decades (reviewed Whitford et al., 2002). Cytoskeletal dynamics are required for proper formation and maintenance of both dendritic and axonal branches (reviewed Kobayashi and Mundel, 1998; Gallo, 2011). The cytoskeleton is composed of microtubules (MTs), Wnt inhibitor actin filaments, intermediate filaments, and a myriad of regulators that process, order, modify, and remove these structures in a dynamic way. MTs are the largest and longest of these filaments, and are formed by polymerization of α- and β-tubulin dimers. This polymerization

gives rise to an inherent polarity along microtubules with a plus-end (where new dimers are polymerized) and a minus-end (where dimers are depolymerized) (reviewed Baas and Lin, 2011). The site at which microtubules are nucleated in neurons has PAK6 been an important open question. This has been widely studied in nonneuronal cell types, but because of technical limitations is only recently being addressed in neurons. We have learned from nonneuronal cell types that microtubules are often nucleated at the microtubule-organizing center (MTOC), which is coupled to the centrosome. However, microtubules can also be nucleated from the nuclear envelope, melanosomes, plasma membrane, and the Golgi complex in a process called acentrosomal nucleation (reviewed Vinogradova et al., 2009). MT nucleation at the Golgi has received recent attention as it provides asymmetry in the MT arrays of motile cells and might be important for cell polarization. Four main proteins are thought to be responsible for the MT nucleating ability of the Golgi: γ-tubulin, AKAP450, GM130, and CLASPs, which provide a molecular scaffold for the MT nucleation process (Kollman et al., 2010; Rivero et al., 2009; Efimov et al., 2007).