Thereafter, extracellular aggregates can get internalized to neighboring cells, most likely through endocytosis, allowing them to bind the natively folded protein and seed the misfolding and aggregation process (Frost et al., 2009, Guo and Lee, 2011 and Nonaka et al., 2010). There have also been reports indicating that cell-to-cell spreading may occur through direct cellular contact, involving nanotubes, or mediated by exosomes or microvesicles (Aguzzi and Rajendran, 2009). (3) What are the structural features of seed-competent misfolded proteins? Misfolded

proteins consist of a heterogeneous mixture of aggregates of variable size. Elucidation of which of the different species is responsible for propagating the pathology is complicated by the lack of sufficient knowledge regarding the detailed structure of these aggregates and the dynamic nature of the aggregation

process. Sorafenib mw Considering purely physicochemical characteristics, it seems likely that freely circulating small oligomers may be better seeds; however, larger polymers may be more stable against biological clearance. (4) What MLN0128 supplier are the molecular bases for the selective cellular accumulation of NFTs? Even though spreading of tau pathology may provide a feasible explanation for the mechanism by which deposition of tau aggregates progresses in the brain of AD patients, this phenomenon does not explain why only some of the interconnected neurons develop NFTs. The reason behind the selective

accumulation of different types of misfolded Unoprostone aggregates in distinct brain regions is a major unknown in the field. Possible explanations for this intriguing phenomenon could be the involvement of cellular receptors, the differential functioning of clearance mechanisms, or the distinct level of expression of the proteins involved in misfolding. The finding that tau pathology spreads in the brain by a prion-like mechanism not only helps us understand the process involved in disease pathogenesis and provides a feasible explanation for the stereotypical progression of these lesions in AD brain but may also lead to the identification of new targets for therapeutic intervention. Indeed, preventing the initial formation of seeds or the subsequent spreading of tau aggregates may represent interesting strategies for a much-needed treatment for AD and related tauopathies. “
“A remarkable feature of the peripheral nerve is the ability to regenerate after injury. Regeneration is associated with an extraordinary series of changes in Schwann cells (reviewed in Chen et al., 2007). After injury, Schwann cells dedifferentiate into a progenitor-like state, proliferate, and repopulate the damaged nerve. In the nerve segment distal to the site of injury, columns of dedifferentiated Schwann cells form the Bands of Bungner and provide an important substrate for regenerating axons. Once axons have regenerated, Schwann cells then redifferentiate and remyelinate.